The Adipose Organ: from Past Discoveries to Future Directions

Points clés à retenir

The Adipose Organ Beyond Energy Storage

Adipose tissue is an active organ with metabolic and endocrine functions. White adipocytes store energy and produce hormones involved in energy regulation, while brown adipocytes specialise in heat production. Understanding these complementary functions provides a broader perspective on adipose tissue in health and disease.

Adipose Tissue Plasticity and Adaptation

The presentation explored the capacity of adipose tissue to change in response to physiological and environmental demands. Examples included white-to-brown adipocyte conversion and the speaker’s proposed account of mammary tissue remodelling during pregnancy and lactation. These processes highlighted plasticity as an important area of adipose biology research.

Adipocyte Enlargement, Cell Death, and Inflammation

Adipocyte enlargement can be accompanied by cellular stress and dysfunction. The session illustrated how macrophages surround dead adipocytes to form crown-like structures, linking changes in tissue architecture with chronic inflammation and metabolic complications associated with obesity.

The Importance of Visceral Fat and Fibrosis

The location and condition of adipose tissue matter alongside its overall amount. The presentation highlighted the vulnerability of visceral fat to inflammation and fibrosis, and explored how collagen remodelling may contribute to impaired tissue expansion, hypoxia, and adipocyte death.

Connecting Structural Discoveries with Therapeutic Research

Microscopy provides valuable insights into the relationship between adipose tissue structure and function. The session discussed approaches intended to promote browning or reduce adipocyte enlargement, while highlighting research questions about their translation into meaningful clinical benefits. Discussion also emphasised choosing experimental models that suit the specific research question.

Orientations futures et prochaines étapes

• Investigate the mechanisms regulating adipose tissue plasticity and how these are altered in obesity.
• Explore whether reducing adipocyte enlargement and preserving tissue function can improve metabolic health.
• Further examine the relationships between collagen regulation, fibrosis, inflammation, and adipocyte death, particularly in visceral fat.
• Evaluate approaches targeting adipose tissue browning, distinguishing experimental findings from demonstrated clinical benefits.
• Develop research models that better capture adipose tissue architecture, cellular interactions, and communication with other organs.
• Encourage collaboration across anatomy, cell biology, metabolism, and clinical research to translate discoveries into improved understanding and management of obesity.

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WEBVTT

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Okay. So hello everyone and welcome to this EASO Early Career

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Network e-Learning Hub webinar. This is our monthly webinar

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series, and thank you very much for joining us.

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Today’s session is called The Adipose Organ: From Past Discoveries to Future

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Directions. We’ll explore the discoveries that have shaped our understanding of the

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adipose organ, its role in obesity and metabolic diseases, and future directions

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for research. My name is Giorgia Colledluori, and I am a board member of the ECN

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Board. And I’m pleased to be hosting today’s session alongside my fellow board

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member, Emil Hidayatli.

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Before we begin, we’d like to acknowledge that the Novo Nordisk Foundation has

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monthly webinar series, supporting knowledge sharing and skill development among

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any early career colleague who may be interested in joining us.

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A few practical points before we get started.

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But before I introduce our speaker, I’ll hand over to Emil, who’s going to share a

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few ECN updates and opportunities. Please, Emil.

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Thank you so much, Giorgia. Hello, everyone. My name is Emil Hidayatli.

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I’m also the board member of EASO ECN, and I’m very

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happy to share some news that will aid all of you.

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Before we begin, I would like to share a few opportunities for ECN members.

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We’ll put a link in the chat with further details.

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First, abstract submissions for the European Congress on Obesity are open until

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15 January 2027. The Congress will take place in Munich from

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18 to 21 May 2027. The ECN Best Thesis

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Award is also open for submissions.

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If you are nearing completion of your thesis or have recently completed it, please

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consider applying by 10 January 2027.

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Three finalists will present their work at a dedicated session at

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ECO 2027, and the winner will receive a 500 euro cash prize.

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Applications for the EASO Novo Nordisk Foundation New Investigator Awards are open

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until Monday, 14th December. Four research grants of

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300,000 Danish crowns, which is approximately 4,000 euros

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each, are available across basic science, clinical research, childhood obesity, and

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public health. Winners will also receive support and attend at present

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ECO 2027 in Munich. We encourage eligible early career researchers to

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consider applying. Our ECN Spotlight highlights members and their research

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through the EASO website and social media, reaching the wider obesity community.

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If you would like your work to be featured, please get in touch.

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And finally, we have been delighted to welcome you at our ECN WhatsApp

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group, group for quick updates, sharing resources, and connecting with other

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members across Europe. Thank you, and back to you,

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Giorgia.

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Thanks a lot, Emil. So it’s now my pleasure to welcome Professor Saverio Schini

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from the Center for Obesity of Marche Polytechnic University in Italy.

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He’s also affiliated at the University of Copenhagen and distinguished professor

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emeritus at the University of Bonn.

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Professor Schini is internationally recognized for his pioneering research into

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adipose tissue biology and for advancing the concept of the adipose organ.

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His work has helped shape our understanding of how adipose tissue functions in

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health and disease. And I’m especially pleased to introduce him because even before

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I joined his lab for my PhD, I seemed to hear his name everywhere.

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So his work appeared in papers after papers, and people often spoke of him as a

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kind of magician of the adipose tissue microscopy.

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So that reputation is part of me, so it’s a real pleasure for me to introduce him

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today. So Professor Schini, please, I’ll hand it over to you.

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Thank you very much for this invitation.

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So I should share my screen.

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D'accord.

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I do not have any conflict of interest.

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Et

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we are all aware that

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le

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definition of adipocyte is a simple definition

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of a cell containing

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lipids. But we have different types

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containing lipids. So if they have a different

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anatomy, they have a different function.

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White

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adipocyte

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are spherical cells.

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90% of their volume is occupied by single

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lipid droplets, and their main function is provide

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the organisms with highly energetic molecules,

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mainly fatty acids,

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because the most important organ of our organism

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use this type of energetic molecules that are very

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important for survival. But this cell is also

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an endocrine cell producing a lot of very important

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hormones.

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Leptin, discovered 30 years ago, everybody knows about

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this hormone that is also called the voice of the

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adipose tissue because it’s telling the brain how

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much

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energy reserve under the form of adipose tissue is present

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in the organism. So if the storage is low,

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leptin is low, the brain tend to force the

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search for food. And without leptin, obesity is

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the consequence.

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But

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administration of leptin can restore the normal phenotype.

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More recently,

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another very important hormone was discovered, asporosin, that is

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also produced by adipocytes during fasting.

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And this hormone allows the food intake.

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Look at this lady with

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a very low amount of fat, therefore with a

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very low level of leptin, but does not eat because of the

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lack of ghrelin.

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Therefore, important hormones for the brain, but also

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important hormones for the food utilization in

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the peripheral organs.

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Brown adipocytes

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have a different type of lipid accumulation, multilocular,

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and among the lipids, a lot of mitochondria, very

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special mitochondria. And the function of mitochondria is

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explaining the function of brown adipocyte.

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In the normal mitochondria, look at the morphology of normal mitochondria.

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In the normal mitochondria, the oxidation of substrate

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creates a

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proton gradient in the external part of a mitochondria.

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So these protons tend to go in the matrix of the mitochondria,

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but cannot pass the membrane, so they are obliged to

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pass into this enzymatic channel.

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And the energy of the flux of these protons is

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used to produce ATP. So this is the function of normal mitochondria.

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In brown mitochondria, look at the morphology, the very different

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morphology of brown mitochondria.

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In the brown mitochondria, the adrenergic stimulation induces the

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oxidation of fatty acids. And also here, there is the

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production of the gradient of protons.

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But here, we have

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a specific protein called UCP1 that is

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uniquely expressed in this mitochondria that

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allow a free passage of protons. Therefore,

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all the intrinsic energy into the fatty acid

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burned in the mitochondria goes produce heat.

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And the heat production is very important because the normal temperature

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for the normal functionality of cells is quite

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high, and there does not exist a single

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area in the

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world in which thermogenesis is never

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necessary.

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So two cell type, very different, with a

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different function,

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almost opposite function. And the question is: Where are located

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in the organism?

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In my opinion, this is a

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reasonable definition for a organ.

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First of all, an organ must be dissectable and

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formed by different tissues with different functions,

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but with a finalistic role.

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This is the very first demonstration that adipose

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tissues are dissectable, that I presented

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last century.

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And this demonstration

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already showed that the white and brown adipose tissue

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are contained in the same organ. And more recently,

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we were able to demonstrate that it’s possible to

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dissect the whole adipose organ as a

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unitary structure.

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What about humans? Using these four digital

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bodies, we were able to make digital dissection

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and extrapolate the areas containing fat, and

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with the serial section, reconstruct the human adipose

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organ. And it’s evident how similar is the

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adipose organ in the distribution of subcutaneous,

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visceral, and even brown adipose tissue.

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And this raises the question if the

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brown adipose tissue in humans is active.

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Look at this lady. At that time, she was 31, with

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no glucose uptake at the root of the neck

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during summer at 28 degree centigrade.

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And look at the uptake after two hours

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at 19 degree centigrade. And during

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chronic exposure in winter, look at the

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strong

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glucose uptake, not only in the root of the neck, but also in

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the mediastinum. And we showed that in this region,

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there is a real brown adipose tissue.

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And we found it in all people below 30, in

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20, 30% of people around 50, and even in

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one 60-year-old person,

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mainly in leaner persons, but also in overweight.

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But which cooperation? And with this question in mind, we

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look at the adipose organ in different environmental situation.

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And look

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at the difference in the color of the adipose organ after

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10 days of cold exposure. And from a quantitative

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point of view,

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look at the

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total amount of adipocytes in the adipose

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organ in two different strains do not change after

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cold exposure. Of course, we have an increase in the

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brown part, explaining the changement in the color,

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but we have also an equivalent reduction in the white

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part. So how to interpret this result?

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That we were right when, 26 years ago, we

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proposed that white adipocyte can directly

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convert into brown adipocyte with the beta-3

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agonist administration. And we confirmed this

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conversion in vivo

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in animals cold exposed. And in this experiment,

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we found the cells that we consider as

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markers of the direct conversion of white into brown.

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It has cells with intermediate shape

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between white and brown, but with the marker of

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the brown activity, the UCP1.

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And the phenomenon of conversion was blunted in

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animals without the beta-3 receptors.

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So,

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the answer to the question, in our opinion, is that

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animals have an organ containing the two tissue.

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When the animal is exposed to cold, brown make thermogenesis.

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But when it’s exposed to chronic cold, then you have a

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conversion of white into brown to help

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thermogenesis. On the other hand, when you have a normal diet, white make

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its job. But when you have an obesogen diet,

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then brown convert

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into white in order to help for the

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storage of the precious energy, because the

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organism does not know if there will be a fasting period.

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So, this

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conversion ability is the cooperation between white

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and brown, in our opinion.

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Any clinical significance? Yes, because look at what

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happen in animals without the beta receptor,

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beta-less animals. Brown convert into

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white,

231
00:20:01.650 –> 00:20:07.530
expressing the genes of white and reducing the

232
00:20:07.590 –> 00:20:12.210
brown genes. And in these animals, without

233
00:20:13.560 –> 00:20:18.660
a functional brown adipose tissue, in few weeks, develop

234
00:20:18.780 –> 00:20:24.361
obesity. Therefore, brown is important

235
00:20:24.720 –> 00:20:26.790
to prevent obesity.

236
00:20:28.140 –> 00:20:33.780
But it’s also important to prevent diabetes, it’s important to

237
00:20:33.840 –> 00:20:37.621
prevent atherosclerosis. And look,

238
00:20:39.210 –> 00:20:43.560
just this year was published four

239
00:20:45.540 –> 00:20:51.030
papers dealing with the ability of brown adipose tissue

240
00:20:52.111 –> 00:20:58.051
to help function in the heart, in the liver, in the prostate,

241
00:20:58.470 –> 00:21:00.301
and even in the bone.

242
00:21:02.160 –> 00:21:07.530
So it’s not surprising that brown adipose tissue allow a

243
00:21:07.890 –> 00:21:09.270
longer survival.

244
00:21:11.310 –> 00:21:14.551
But what about transdifferentiation in human?

245
00:21:15.450 –> 00:21:20.730
This is the normal morphology of a human omentum,

246
00:21:22.350 –> 00:21:26.790
composed uniquely by white adipocyte.

247
00:21:27.479 –> 00:21:32.490
And look what happen to this tissue in people with a

248
00:21:32.580 –> 00:21:36.030
pheochromocytoma. That is a

249
00:21:37.500 –> 00:21:43.380
benign neoplasia producing high amount of

250
00:21:43.500 –> 00:21:46.710
adrenaline and noradrenaline.

251
00:21:49.051 –> 00:21:54.840
This is what happen. A clear conversion of white into

252
00:21:54.900 –> 00:21:59.790
brown. And we found not only the presence of

253
00:22:00.390 –> 00:22:05.880
classic brown adipocyte, UCP1 positive, of course,

254
00:22:06.330 –> 00:22:11.970
but also a lot of the marker of the direct

255
00:22:12.060 –> 00:22:17.910
conversion of white into brown. And look at the electron

256
00:22:18.000 –> 00:22:23.850
microscopy of this cell type. Enlargement of the cytoplasm,

257
00:22:24.540 –> 00:22:29.970
showing the presence of white mitochondria,

258
00:22:30.990 –> 00:22:35.551
brown mitochondria, and mitochondria with

259
00:22:36.121 –> 00:22:41.220
intermediate shape. And look at this intermediate

260
00:22:41.700 –> 00:22:44.371
mitochondria, with in part

261
00:22:45.900 –> 00:22:46.440
white

262
00:22:47.910 –> 00:22:51.840
and in part brown morphology.

263
00:22:55.500 –> 00:23:01.111
From a molecular point of view, our idea

264
00:23:01.470 –> 00:23:07.020
is that these dual-phase cells have a

265
00:23:07.200 –> 00:23:12.600
lot of molecules that interfere

266
00:23:13.801 –> 00:23:18.750
with the brown phenotype. And when you activate the

267
00:23:18.960 –> 00:23:24.630
beta-3 receptor, you inhibit all of

268
00:23:24.690 –> 00:23:29.070
these inhibitor, allowing the brown phenotype.

269
00:23:32.190 –> 00:23:35.700
But there is any other way

270
00:23:37.170 –> 00:23:41.040
for browning? Yes, physical activity.

271
00:23:41.850 –> 00:23:47.730
Of course, physical activity induce a reduction in the size of

272
00:23:47.790 –> 00:23:50.700
the adipocyte, but also browning.

273
00:23:51.361 –> 00:23:57.330
And we found an increased amount of noradrenergic fibers

274
00:23:57.780 –> 00:24:00.510
density in the adipose organ.

275
00:24:02.371 –> 00:24:08.220
Furthermore, I had the opportunity to participate to this discover of

276
00:24:08.280 –> 00:24:10.170
Bruce Spiegelman, that

277
00:24:12.210 –> 00:24:17.670
skeletal muscle, during physical activity, produce a

278
00:24:17.730 –> 00:24:21.930
hormone that is able to induce browning.

279
00:24:25.080 –> 00:24:31.020
Nowadays, everybody agree with the browning

280
00:24:31.080 –> 00:24:36.810
possibility. But when I presented for the first time this data

281
00:24:37.170 –> 00:24:42.750
20, 30 years ago, people was asking me for

282
00:24:42.900 –> 00:24:48.330
other examples. So we looked for other example, and we

283
00:24:48.450 –> 00:24:53.700
found in the adipose organ another eclatant example,

284
00:24:54.450 –> 00:24:57.990
the mammary gland. What is the mammary gland?

285
00:24:58.680 –> 00:25:04.170
In mice, the whole subcutaneous depot is a

286
00:25:04.260 –> 00:25:10.230
mammary gland. In women, only part of this thoracic

287
00:25:10.320 –> 00:25:14.190
subcutaneous fat form the mammary gland.

288
00:25:15.180 –> 00:25:20.700
That is just subcutaneous fat infiltrated

289
00:25:21.240 –> 00:25:26.040
by branched ducts ending in a nipple.

290
00:25:26.940 –> 00:25:32.730
Therefore, two nipples in women and 10

291
00:25:32.850 –> 00:25:35.040
nipples in mice.

292
00:25:36.330 –> 00:25:38.220
In virgin

293
00:25:39.660 –> 00:25:44.970
mice, 90% of the volume is composed by

294
00:25:45.120 –> 00:25:50.760
adipose tissue infiltrated by these ducts, no

295
00:25:50.910 –> 00:25:56.790
alveoli. The alveoli producing milk develop

296
00:25:56.970 –> 00:26:02.821
only during pregnancy, with a clear reduction in the

297
00:26:02.910 –> 00:26:08.821
amount of fat. And during lactation, only

298
00:26:08.910 –> 00:26:14.821
a small amount of fat, almost 90% composed

299
00:26:14.880 –> 00:26:20.280
by alveoli and ducts. And in the post-lactation,

300
00:26:20.790 –> 00:26:23.790
reappear the adipocyte.

301
00:26:25.560 –> 00:26:28.321
With these five papers,

302
00:26:30.060 –> 00:26:30.301
we

303
00:26:32.220 –> 00:26:37.770
support the idea that during pregnancy, the

304
00:26:37.890 –> 00:26:43.020
adipocyte give rise to the alveoli,

305
00:26:44.730 –> 00:26:50.400
and these alveolar cells producing milk are

306
00:26:50.520 –> 00:26:56.370
very rich of lipid droplets. Why? Because

307
00:26:56.460 –> 00:27:00.571
they derive from the

308
00:27:02.491 –> 00:27:08.340
conversion of adipocyte into epithelial cells.

309
00:27:08.730 –> 00:27:11.760
And look at the amount of lipids in this cell.

310
00:27:12.060 –> 00:27:16.950
Therefore, these cells can be called adipocyte.

311
00:27:17.430 –> 00:27:23.400
And because the adipose organ during pregnancy and lactation

312
00:27:23.970 –> 00:27:29.220
is pink, I call these cells pink adipocyte.

313
00:27:30.438 –> 00:27:35.958
And in the post-lactation period, the epithelial

314
00:27:36.167 –> 00:27:41.268
cells of the alveoli convert again to

315
00:27:41.899 –> 00:27:47.538
adipocyte, white and brown. And this is supported by

316
00:27:48.108 –> 00:27:49.758
several experiments.

317
00:27:51.318 –> 00:27:56.839
So together with the browning of the adipose

318
00:27:56.958 –> 00:28:02.389
organ, we have also the pinking of the adipose organ,

319
00:28:02.958 –> 00:28:08.328
but also the whitening of the adipose organ in

320
00:28:08.478 –> 00:28:10.938
animals with obesity.

321
00:28:12.198 –> 00:28:16.188
And in the tissues with obesity,

322
00:28:18.649 –> 00:28:19.038
these

323
00:28:20.718 –> 00:28:25.458
papers showed that there is an

324
00:28:26.508 –> 00:28:32.298
inflammation, chronic low-grade inflammation made

325
00:28:32.419 –> 00:28:37.128
by macrophages. And this is very important because it is

326
00:28:37.518 –> 00:28:43.218
associated with the development of the insulin resistance.

327
00:28:44.958 –> 00:28:50.118
But they did not say why macrophages

328
00:28:50.779 –> 00:28:55.788
are infiltrating the adipose tissue with obesity.

329
00:28:56.508 –> 00:29:02.478
So we looked where are located the macrophages in

330
00:29:02.538 –> 00:29:07.908
the adipose tissue, and we found that macrophages form these

331
00:29:08.419 –> 00:29:14.328
crown-like structures, and that these crown-like structures

332
00:29:14.508 –> 00:29:19.818
are present also in normal lean

333
00:29:20.419 –> 00:29:26.238
adipose tissue, but 25, 30 times more

334
00:29:26.928 –> 00:29:31.188
in the adipose tissue with obesity.

335
00:29:32.839 –> 00:29:38.508
So considering that 90% of the macrophages are

336
00:29:38.779 –> 00:29:40.818
in these crown-like structures,

337
00:29:42.198 –> 00:29:47.718
studying these crown-like structures should reveal the secret for this

338
00:29:47.839 –> 00:29:53.718
infiltration, and this is the transmission electron microscopy of the

339
00:29:53.779 –> 00:29:58.758
crown-like structures, and we will see an enlargement now.

340
00:30:00.318 –> 00:30:05.389
And in normal adipocyte, we have a lipid droplet.

341
00:30:06.108 –> 00:30:11.958
We have the thin cytoplasmic rim containing the organelles,

342
00:30:12.408 –> 00:30:17.419
and external to the rim, we have the basal membrane.

343
00:30:18.408 –> 00:30:24.078
In the crown-like structure, we have the lipid droplet, we have the

344
00:30:24.169 –> 00:30:27.738
basal membrane, but where is the adipocyte?

345
00:30:28.158 –> 00:30:33.798
No adipocyte, only debris of a dead

346
00:30:33.948 –> 00:30:39.468
adipocyte into the macrophages that are clearly

347
00:30:39.558 –> 00:30:44.598
reabsorbing the debris of the dead adipocyte.

348
00:30:47.298 –> 00:30:52.608
Another important issue dealing with obesity

349
00:30:53.419 –> 00:30:56.328
is why the visceral

350
00:30:57.828 –> 00:31:02.839
adipose tissue is more morbid than

351
00:31:02.899 –> 00:31:04.188
subcutaneous.

352
00:31:06.678 –> 00:31:07.728
Recently, it

353
00:31:09.108 –> 00:31:15.018
was shown that even in people with a normal BMI,

354
00:31:15.798 –> 00:31:20.389
if they have an increase of the visceral fat,

355
00:31:21.258 –> 00:31:26.328
increase the risk for mortality and for

356
00:31:26.419 –> 00:31:31.488
cardiovascular disease. So the visceral fat is very

357
00:31:31.518 –> 00:31:32.538
important.

358
00:31:34.458 –> 00:31:40.399
And we looked at the differences between subcutaneous and visceral.

359
00:31:41.208 –> 00:31:47.178
Regarding the size, the size in animals with obesity

360
00:31:47.928 –> 00:31:49.399
is more

361
00:31:50.658 –> 00:31:56.538
enlarged in subcutaneous fat. And considering that

362
00:31:56.779 –> 00:32:02.208
there is a positive correlation between size and inflammation,

363
00:32:03.738 –> 00:32:09.348
we expected more inflammation in subcutaneous, but was the

364
00:32:09.408 –> 00:32:15.228
reverse, more inflammation in visceral than subcutaneous,

365
00:32:17.419 –> 00:32:22.578
suggesting that the visceral adipocyte have a

366
00:32:22.698 –> 00:32:27.378
critical size triggering that smaller

367
00:32:28.488 –> 00:32:30.618
than subcutaneous fat.

368
00:32:32.899 –> 00:32:33.438
Why?

369
00:32:35.658 –> 00:32:41.089
We have to consider that a large proportion of the

370
00:32:41.178 –> 00:32:46.188
visceral fat is made up by brown

371
00:32:46.368 –> 00:32:51.438
adipocyte. So the idea was that

372
00:32:52.308 –> 00:32:57.678
a large proportion of the visceral fat derive from

373
00:32:57.738 –> 00:33:00.858
conversion of brown into white.

374
00:33:02.928 –> 00:33:06.858
And we demonstrate that when you

375
00:33:07.068 –> 00:33:11.988
convert brown adipocyte into

376
00:33:12.048 –> 00:33:17.298
white-like adipocyte, in this case, we knock out our lipolytic

377
00:33:17.389 –> 00:33:18.078
enzyme.

378
00:33:20.178 –> 00:33:26.058
These transformed brown adipocyte are very fragile,

379
00:33:26.208 –> 00:33:28.458
so allowing a

380
00:33:29.868 –> 00:33:31.908
inflammasome situation.

381
00:33:33.288 –> 00:33:35.328
And comparing

382
00:33:36.858 –> 00:33:42.498
the adipocyte derived from brown conversion

383
00:33:42.649 –> 00:33:47.208
into white with those derived from

384
00:33:48.529 –> 00:33:54.438
normal white adipocyte, it was evident that those derived

385
00:33:54.978 –> 00:34:00.919
from brown adipocyte are more inflammasome with higher level of

386
00:34:00.978 –> 00:34:01.878
inflammation.

387
00:34:03.197 –> 00:34:07.008
What about humans? Exactly the same thing.

388
00:34:08.029 –> 00:34:13.578
Subcutaneous larger than visceral, but visceral more inflamed than

389
00:34:13.669 –> 00:34:16.248
subcutaneous. Thus,

390
00:34:20.449 –> 00:34:22.368
the problem with this

391
00:34:24.468 –> 00:34:30.138
adipose tissue with obesity is the hypertrophy

392
00:34:30.319 –> 00:34:35.899
of the adipocyte. These hypertrophic adipocyte are stressed

393
00:34:36.468 –> 00:34:40.788
and show a lot of alteration in several organelles,

394
00:34:41.868 –> 00:34:47.748
mainly in the visceral fat. And then these cells produce a

395
00:34:47.839 –> 00:34:53.538
chemoattractant for macrophages, and at the end die,

396
00:34:54.378 –> 00:35:00.318
and the visceral die before subcutaneous and form these

397
00:35:00.408 –> 00:35:06.348
crown-like structures with a long-term reabsorption

398
00:35:06.798 –> 00:35:12.558
of the large debris and with the production of toxins that have

399
00:35:13.068 –> 00:35:15.288
several collateral effect.

400
00:35:16.578 –> 00:35:22.488
Fibrosis is another important feature of the adipose

401
00:35:22.548 –> 00:35:24.708
tissue with obesity,

402
00:35:26.148 –> 00:35:29.748
with several metabolic consequences.

403
00:35:30.768 –> 00:35:36.378
We have three type of collagen in adipose tissue,

404
00:35:37.668 –> 00:35:43.398
type I and III, that is fibrillar, and type VI that is

405
00:35:43.458 –> 00:35:48.828
not fibrillar and not visible with the normal transmission electron

406
00:35:48.888 –> 00:35:49.758
microscopy.

407
00:35:50.988 –> 00:35:54.318
And we recently found that

408
00:35:55.728 –> 00:36:01.608
in people with obesity, there is fibrosis mainly

409
00:36:01.728 –> 00:36:03.438
in the visceral fat.

410
00:36:04.968 –> 00:36:10.188
And transmission electron microscopy, scanning electron

411
00:36:10.248 –> 00:36:15.858
microscopy, and in vitro experiment show that

412
00:36:16.428 –> 00:36:21.768
the fibros of this fibrosis derive

413
00:36:22.279 –> 00:36:25.279
directly from adipocyte

414
00:36:26.538 –> 00:36:31.938
with an increase of the fibrillar collagen, but with a

415
00:36:31.998 –> 00:36:37.848
reduction of the collagen VI. And what is the meaning of

416
00:36:37.938 –> 00:36:43.518
this reduction? We found in three rare

417
00:36:44.334 –> 00:36:50.244
Patients with congenital reduction of collagen

418
00:36:50.394 –> 00:36:55.525
VI, that there is a fibrosis of the adipose tissue,

419
00:36:56.034 –> 00:36:59.664
very high level of fibrosis.

420
00:37:01.974 –> 00:37:06.954
Thus, the idea is that in

421
00:37:07.105 –> 00:37:11.904
adipocyte, in order to counteract this

422
00:37:12.504 –> 00:37:18.144
pressure toward the external part of the cell,

423
00:37:18.924 –> 00:37:20.814
the cell produce a

424
00:37:22.434 –> 00:37:26.514
fibrillar network in order to resist.

425
00:37:27.414 –> 00:37:27.804
Et

426
00:37:29.334 –> 00:37:34.855
this fibrillar network is stabilized by collagen

427
00:37:34.944 –> 00:37:35.394
VI.

428
00:37:36.624 –> 00:37:40.014
That is like a clue that

429
00:37:41.364 –> 00:37:47.034
support this network and induce reduction of collagen I

430
00:37:47.544 –> 00:37:53.244
and III. But the cell must expand

431
00:37:53.454 –> 00:37:59.424
physiologically and produce leptin that have an inhibitory

432
00:37:59.964 –> 00:38:05.004
effect on collagen VI. So for the physiological

433
00:38:05.605 –> 00:38:10.944
expansion of the adipocyte, leptin reduce the

434
00:38:11.034 –> 00:38:13.105
activity of collagen

435
00:38:14.454 –> 00:38:20.394
VI. But when you have a drastic reduction of collagen VI, then you

436
00:38:20.543 –> 00:38:26.454
have a drastic increase in the production of collagen I and

437
00:38:26.784 –> 00:38:31.644
III with fibrosis, causing

438
00:38:31.704 –> 00:38:35.154
hypoxia of these cells and death,

439
00:38:36.924 –> 00:38:38.394
with inducing

440
00:38:39.624 –> 00:38:44.634
inflammation and with other metabolic

441
00:38:44.754 –> 00:38:49.494
consequence in further inducing fibrosis.

442
00:38:50.244 –> 00:38:53.994
Therefore, together with the death

443
00:38:55.794 –> 00:39:01.164
that I presented before, we reason now to add another

444
00:39:01.254 –> 00:39:06.804
type of death of the adipocyte, reinforcing the

445
00:39:08.484 –> 00:39:09.355
pathologic

446
00:39:10.824 –> 00:39:13.974
consequences of this situation.

447
00:39:16.254 –> 00:39:21.744
Is there any drug that could reverse the situation?

448
00:39:23.484 –> 00:39:29.364
Beta 3 agonist are already available and are

449
00:39:29.544 –> 00:39:35.244
able to induce activation of the brown

450
00:39:35.424 –> 00:39:38.874
adipose tissue. But also,

451
00:39:41.034 –> 00:39:46.794
A2A receptor agonist could have

452
00:39:46.884 –> 00:39:52.194
this important browning effect on the adipocyte.

453
00:39:53.244 –> 00:39:59.184
Inhibitors of CD38 inducing an activation of the

454
00:39:59.273 –> 00:40:04.794
pathway of sirtuins also. And the recent

455
00:40:05.964 –> 00:40:10.434
tirzepatide have also browning effect.

456
00:40:11.574 –> 00:40:17.304
So in conclusion, we have several arms in order to

457
00:40:18.624 –> 00:40:24.534
counteract this situation, favoring the

458
00:40:24.594 –> 00:40:30.414
browning of the adipose tissue. Of course, this

459
00:40:31.584 –> 00:40:33.654
with the help of my

460
00:40:34.914 –> 00:40:38.694
group that is following me since

461
00:40:40.254 –> 00:40:41.334
50 years

462
00:40:43.134 –> 00:40:43.554
et

463
00:40:44.814 –> 00:40:47.694
all this international collaboration.

464
00:40:48.234 –> 00:40:51.954
And thank you very much for your attention.

465
00:40:54.714 –> 00:40:59.244
Thank you very much, Professor Scibini, for this beautiful presentation and for

466
00:41:01.014 –> 00:41:06.714
walking us through the major discoveries into the biology of

467
00:41:06.775 –> 00:41:12.355
adipose tissue, the concept of the adipose organ, up to the drug development.

468
00:41:12.954 –> 00:41:15.775
So, the floor is now open for questions.

469
00:41:15.864 –> 00:41:21.054
I remind everybody that you can type your question in the Q&A, in the chat,

470
00:41:21.174 –> 00:41:23.814
basically. So this is our Q&A moment.

471
00:41:24.954 –> 00:41:30.504
But while waiting for some questions, I’m going to break the ice and ask one

472
00:41:30.834 –> 00:41:35.304
question myself. I don’t know, Emil, if you have any question, please just turn on

473
00:41:35.484 –> 00:41:36.054
your mic.

474
00:41:37.494 –> 00:41:43.434
My question is related to the last set of data that you presented concerning the

475
00:41:44.874 –> 00:41:50.184
collagen VI, and in general, fibrosis of the adipose tissue that is mainly

476
00:41:50.694 –> 00:41:56.424
associated with adipocytes in the mental adipose tissue,

477
00:41:56.484 –> 00:41:59.784
basically, of the omentum. So I was wondering,

478
00:42:01.284 –> 00:42:07.105
are there studies or are you planning to study their association with the

479
00:42:07.164 –> 00:42:10.644
intra-abdominal pressure in patients?

480
00:42:10.855 –> 00:42:16.374
Is it something that is feasible? Is it something that you believe may have

481
00:42:16.464 –> 00:42:22.224
implication for other diseases of the– Because thinking of all the

482
00:42:22.254 –> 00:42:24.444
complication of obesity that interests

483
00:42:25.734 –> 00:42:31.584
organs that are located there, this is something that came up to my mind to

484
00:42:31.644 –> 00:42:32.094
have a

485
00:42:33.474 –> 00:42:34.764
translational also

486
00:42:36.924 –> 00:42:42.294
outcome. And I was wondering also if you studied the

487
00:42:42.355 –> 00:42:48.294
association between fibrosis and macrophages forming the crown-like

488
00:42:48.355 –> 00:42:53.154
structures. Is there an association between these two processes, or are they two

489
00:42:53.544 –> 00:42:54.744
different processes?

490
00:42:56.574 –> 00:43:00.624
Yeah, I think it’s a different situation,

491
00:43:02.994 –> 00:43:08.124
because the crown-like structure is a

492
00:43:08.214 –> 00:43:12.804
reaction to the death of the adipocyte.

493
00:43:13.494 –> 00:43:19.374
So the first event in the formation of

494
00:43:19.494 –> 00:43:24.744
crown-like structure is the death of the adipocyte due

495
00:43:25.434 –> 00:43:30.804
to a specific, I have no time to explain all the details,

496
00:43:31.284 –> 00:43:31.525
but

497
00:43:32.964 –> 00:43:37.855
with a specific type of death that is pyroptosis,

498
00:43:38.724 –> 00:43:40.525
induced by several

499
00:43:43.014 –> 00:43:48.504
mechanisms, including, for example, the presence of

500
00:43:49.134 –> 00:43:54.684
cholesterol crystals. You know that during this

501
00:43:56.064 –> 00:44:01.704
progressive hypertrophy of the adipocyte, there is an increase

502
00:44:02.484 –> 00:44:08.004
in the concentration of cholesterol into the cell, and this cholesterol

503
00:44:08.784 –> 00:44:08.964
dans

504
00:44:10.374 –> 00:44:15.954
the hypertrophic adipocyte form crystals, and crystals are

505
00:44:16.074 –> 00:44:21.804
one of the causes for the activation

506
00:44:22.464 –> 00:44:24.444
of the inflammasome

507
00:44:25.704 –> 00:44:29.634
pathway inducing the death for pyroptosis.

508
00:44:30.084 –> 00:44:35.124
In fibrosis, the situation is completely different because,

509
00:44:36.084 –> 00:44:41.124
I don’t know if you have noticed, that the fibrils

510
00:44:42.804 –> 00:44:47.844
surrounding the adipocyte are directly produced by the

511
00:44:47.904 –> 00:44:53.244
adipocyte. And during fibrosis, there is an increased

512
00:44:53.364 –> 00:44:58.944
amount of these fibrils. So at the end is the

513
00:45:03.684 –> 00:45:09.294
big amount of fibrils inducing hypoxia of the

514
00:45:09.384 –> 00:45:14.394
adipocyte and then the death. So are two completely different

515
00:45:14.484 –> 00:45:16.884
situation, in my opinion.

516
00:45:18.954 –> 00:45:19.284
I see.

517
00:45:21.264 –> 00:45:21.744
Giorgia?

518
00:45:22.134 –> 00:45:22.344
Oui.

519
00:45:23.004 –> 00:45:28.284
Yeah. Professor Scibini, thank you very much for a brilliant presentation.

520
00:45:28.734 –> 00:45:34.674
I have one question, and I also see in our Q&A chat, Yelena and Apra also have the

521
00:45:34.734 –> 00:45:36.084
same also question.

522
00:45:38.064 –> 00:45:42.264
What has the biggest impact on browning of the adipose tissue?

523
00:45:42.384 –> 00:45:46.974
I will add something. Can you suggest some practical option?

524
00:45:47.394 –> 00:45:48.084
For example

525
00:45:49.596 –> 00:45:52.206
… cold temperature or physical activity.

526
00:45:52.356 –> 00:45:58.116
If we can summarize some points that really we can say that it

527
00:45:58.177 –> 00:46:00.966
could help browning the adipose tissue.

528
00:46:01.806 –> 00:46:01.866
Oui.

529
00:46:01.896 –> 00:46:02.286
Merci.

530
00:46:02.916 –> 00:46:07.567
Yes. The main factors are the

531
00:46:08.616 –> 00:46:10.026
cold exposure.

532
00:46:11.466 –> 00:46:16.506
I had the opportunity to study the adipose tissue from

533
00:46:16.596 –> 00:46:22.236
autopsy from people living in Siberia, and we

534
00:46:22.326 –> 00:46:28.026
found that a very high percentage

535
00:46:28.506 –> 00:46:34.266
of the visceral adipose tissue in those subjects is formed

536
00:46:34.326 –> 00:46:39.427
by brown adipocyte. And we found

537
00:46:39.936 –> 00:46:45.516
even a different from people living in Siberia, but

538
00:46:45.756 –> 00:46:50.286
with outdoor working and people

539
00:46:51.427 –> 00:46:56.106
living in Siberia, but with indoor working.

540
00:46:57.006 –> 00:47:02.166
So the chronic cold exposure. But it’s not

541
00:47:02.256 –> 00:47:07.567
necessary to go in Siberia because people living in

542
00:47:07.626 –> 00:47:13.086
Denmark have exactly the same amount of brown

543
00:47:13.146 –> 00:47:15.396
adipose tissue. So,

544
00:47:17.466 –> 00:47:17.886
this

545
00:47:21.096 –> 00:47:26.436
is a clear evidence that chronic cold exposure

546
00:47:27.067 –> 00:47:27.547
make

547
00:47:28.896 –> 00:47:31.356
a sense in this direction.

548
00:47:33.036 –> 00:47:33.427
But

549
00:47:34.716 –> 00:47:39.486
also physical activity. Physical activity

550
00:47:40.206 –> 00:47:45.547
induce an increased activity of the noradrenergic

551
00:47:47.226 –> 00:47:53.047
innervation of the adipose organ and induce browning.

552
00:47:54.817 –> 00:47:58.776
These are the two more important

553
00:48:01.536 –> 00:48:05.976
situation, environment or physiological

554
00:48:06.756 –> 00:48:12.336
situation inducing browning. But now we have

555
00:48:12.666 –> 00:48:13.026
even

556
00:48:14.886 –> 00:48:19.567
commercially available drugs such as

557
00:48:20.226 –> 00:48:25.716
tirzepatide, that has been proved to induce

558
00:48:26.136 –> 00:48:28.026
browning of the

559
00:48:29.317 –> 00:48:30.276
adipocyte.

560
00:48:31.596 –> 00:48:35.196
Thank you very much, Professor. Since there are plenty of questions coming out

561
00:48:35.256 –> 00:48:38.196
through the chat, I’m going to ask you some of those.

562
00:48:38.406 –> 00:48:42.126
So one question is related to the temperature exposure.

563
00:48:42.276 –> 00:48:47.466
Do adipocyte respond also to high temperature and not only to low temperature?

564
00:48:47.736 –> 00:48:49.177
Do you know anything about that?

565
00:48:55.626 –> 00:48:57.636
No, I don’t know.

566
00:48:58.956 –> 00:49:03.906
Okay. There’s not a question, but an appreciation. “Awesome work, Professor Chinti.

567
00:49:03.935 –> 00:49:07.986
It was such an interesting experience of seeing structures rather than just talking

568
00:49:08.047 –> 00:49:12.547
about receptors and functions.” So thank you very much for your images.

569
00:49:12.966 –> 00:49:16.506
This is a comment. I can’t see the people that are commenting.

570
00:49:16.567 –> 00:49:20.106
I’m sorry if I’m not acknowledging you, but I don’t see the names.

571
00:49:21.186 –> 00:49:25.476
Then, I have another question. So thank you very much for the nice, interesting

572
00:49:25.536 –> 00:49:31.206
presentation. The reduction of collagen VI as a response to leptin, an

573
00:49:31.266 –> 00:49:35.016
increase of collagen I and III leading to fibrosis is interesting.

574
00:49:35.496 –> 00:49:40.596
We know that endothrofin, at least in mice, has been associated with

575
00:49:40.656 –> 00:49:46.326
inflammation and fibrosis in the adipose tissue. So this is a comment.

576
00:49:46.506 –> 00:49:49.297
I don’t know if you want to add anything on this comment.

577
00:49:50.886 –> 00:49:54.756
No, that’s a very important aspect.

578
00:49:55.986 –> 00:50:01.386
I think that in the adipose tissue with obesity, there are

579
00:50:01.686 –> 00:50:07.416
these two aspects that are very important, inflammation and fibrosis.

580
00:50:08.106 –> 00:50:13.177
And both are very important, especially in the visceral adipose tissue.

581
00:50:14.646 –> 00:50:18.186
Okay, then we have, “Wonderful talk.

582
00:50:18.547 –> 00:50:23.346
Has any food been linked to changes in adipose metabolism?

583
00:50:24.366 –> 00:50:26.226
In what way, if that, of course?”

584
00:50:28.416 –> 00:50:32.436
Food. Yeah. There is also several

585
00:50:34.536 –> 00:50:35.826
food type that are,

586
00:50:37.776 –> 00:50:41.106
for example, capsaicin, that

587
00:50:43.386 –> 00:50:47.616
are mainly spices, but they

588
00:50:49.596 –> 00:50:52.806
can activate brown adipose tissue.

589
00:50:53.496 –> 00:50:58.927
If you look at the papers by Masayuki Saito, you will

590
00:50:59.016 –> 00:51:04.506
find a lot of details on that. But in my

591
00:51:04.567 –> 00:51:09.276
opinion, the browning effect of the

592
00:51:10.416 –> 00:51:12.036
spices food,

593
00:51:13.566 –> 00:51:19.116
or even other food like menthol, for example,

594
00:51:20.496 –> 00:51:26.256
but is very light in comparison with the cold exposure

595
00:51:26.916 –> 00:51:29.166
or physical exercise.

596
00:51:29.946 –> 00:51:30.427
D'accord.

597
00:51:31.746 –> 00:51:37.057
What is the greatest scientific barrier to translating your important work into

598
00:51:37.177 –> 00:51:42.337
meaningful clinical approaches to obesity management? What’s the greatest barrier?

599
00:51:43.236 –> 00:51:45.547
The greatest is that

600
00:51:46.837 –> 00:51:47.256
when

601
00:51:49.626 –> 00:51:50.196
you know

602
00:51:51.456 –> 00:51:55.596
that you can convert the adipocyte,

603
00:51:57.486 –> 00:52:03.216
you should realize that this conversion can

604
00:52:04.626 –> 00:52:07.057
happen gradually,

605
00:52:08.706 –> 00:52:14.555
should happen gradually, and therefore, the first step

606
00:52:15.277 –> 00:52:21.156
of this conversion will be a reduction in size of the adipocyte.

607
00:52:21.726 –> 00:52:27.666
But this reduction in size per se is very important for the healthy

608
00:52:28.266 –> 00:52:33.876
of your adipose tissue. So if you look at

609
00:52:33.936 –> 00:52:37.656
the recent literature for the

610
00:52:38.916 –> 00:52:43.986
therapy of obesity, you will realize that

611
00:52:44.677 –> 00:52:49.807
most of the pharmaceutical companies are pointing

612
00:52:50.316 –> 00:52:55.956
toward this transformation of white into brown.

613
00:52:56.496 –> 00:53:02.346
Even if, I repeat, it’s not necessary to reach the step

614
00:53:02.736 –> 00:53:08.316
of browning. It is already healthy to reach the first

615
00:53:08.797 –> 00:53:11.646
steps that are reduction in size.

616
00:53:12.636 –> 00:53:12.636
Oui.

617
00:53:14.016 –> 00:53:17.406
Okay. Thank you. So another question.

618
00:53:17.527 –> 00:53:22.807
In obesity, the adipose organ’s ability to convert white to brown appears

619
00:53:22.986 –> 00:53:28.746
blunted. Is that loss of plasticity a cause or a consequence of adipocyte

620
00:53:28.777 –> 00:53:32.286
hypertrophy, death, and crown-like structure formation?

621
00:53:32.797 –> 00:53:38.076
Can it be restored, for example, after weight loss or GLP1 increasing therapy?

622
00:53:41.886 –> 00:53:43.236
No. Can you repeat?

623
00:53:43.266 –> 00:53:43.356
D'accord.

624
00:53:43.777 –> 00:53:45.277
What is the question exactly?

625
00:53:46.027 –> 00:53:46.177
So,

626
00:53:47.496 –> 00:53:52.777
the first comment is that in the adipose organ, the white to brown transition

627
00:53:52.866 –> 00:53:58.536
conversion is blunted usually. And the question is that since there is a loss of

628
00:53:58.566 –> 00:54:04.506
plasticity in the condition of obesity, I’m assuming, the question is that, is this

629
00:54:04.656 –> 00:54:08.557
loss of plasticity a cause or a consequence-

630
00:54:08.677 –> 00:54:08.677
Oh

631
00:54:08.677 –> 00:54:12.277
… or of the hypertrophy, death, and crown-like structure formation?

632
00:54:12.696 –> 00:54:17.527
Can this loss of plasticity be restored through GLP1

633
00:54:19.266 –> 00:54:20.886
increasing therapy or-

634
00:54:20.916 –> 00:54:21.066
Oui.

635
00:54:21.126 –> 00:54:21.456
-loss?

636
00:54:22.027 –> 00:54:23.316
Now I understand. Yes.

637
00:54:24.816 –> 00:54:29.316
When you have a crown-like structure, you cannot go back.

638
00:54:30.216 –> 00:54:34.686
This is a dead adipocyte, so it’s not dealing with that.

639
00:54:34.896 –> 00:54:40.807
Of course, it depends of the amount of crown-like structures you

640
00:54:40.896 –> 00:54:46.686
have. I have seen a visceral adipose tissue,

641
00:54:47.527 –> 00:54:47.856
uh

642
00:54:49.218 –> 00:54:54.829
From a person not with obesity, but was

643
00:54:55.668 –> 00:54:56.658
overweight,

644
00:54:59.088 –> 00:54:59.449
but

645
00:55:01.007 –> 00:55:01.848
assuming

646
00:55:06.018 –> 00:55:10.699
fat in a short period. And the

647
00:55:13.307 –> 00:55:18.679
visceral adipose tissue had an impressive amount of

648
00:55:18.739 –> 00:55:24.228
ground-like structures. So the amount of ground-like structures depends

649
00:55:24.378 –> 00:55:29.748
also by the timing of assuming weight,

650
00:55:31.338 –> 00:55:32.449
gaining weight.

651
00:55:32.929 –> 00:55:33.978
Okay. I don’t know if-

652
00:55:34.218 –> 00:55:40.188
But the adipocyte, even if they are hypertrophic,

653
00:55:40.878 –> 00:55:44.179
they can respond to the

654
00:55:45.468 –> 00:55:50.538
noradrenergic stimulation. Of course, the amount of

655
00:55:50.628 –> 00:55:54.949
receptors depend also from the size.

656
00:55:55.398 –> 00:56:01.068
So the more is larger the cell, the less is responsive.

657
00:56:02.329 –> 00:56:06.468
Thank you. I’m going to rush because we have a few minutes but a lot of questions,

658
00:56:06.498 –> 00:56:08.959
so we’ll try to do our best to answer most of them.

659
00:56:10.429 –> 00:56:15.378
The reduction of collagen VI as a response to leptin and increase of collagen I and

660
00:56:15.378 –> 00:56:21.168
II– No, I’m sorry, those are the same question. I have it again. Sorry.

661
00:56:21.498 –> 00:56:21.679
Oui.

662
00:56:23.209 –> 00:56:27.709
So the main focus of adipose organ physiology has been on the role of adipocyte

663
00:56:27.829 –> 00:56:33.079
place. What are, in your views, the importance of pre-adipocytes in white adipose

664
00:56:33.079 –> 00:56:35.508
tissue and their role in inflammation?

665
00:56:37.429 –> 00:56:42.918
The pre-adipocytes are very important because obesity, the obese

666
00:56:43.248 –> 00:56:47.658
adipose tissue is formed by hypertrophic and

667
00:56:49.038 –> 00:56:54.739
hyperplastic adipose tissue. The more you have hyperplastic

668
00:56:55.398 –> 00:56:59.179
adipose tissue, the less you have inflammation.

669
00:56:59.718 –> 00:57:05.688
So I saw in my life only one case in which the

670
00:57:06.318 –> 00:57:12.018
obesity was just due to hyperplasia, and the

671
00:57:12.228 –> 00:57:15.949
patient was metabolically healthy.

672
00:57:16.518 –> 00:57:22.158
So when we talk about metabolically healthy obesity,

673
00:57:23.688 –> 00:57:29.058
probably we talk about an adipose organ mainly

674
00:57:29.118 –> 00:57:34.699
composed by smaller adipocytes derived from the

675
00:57:34.848 –> 00:57:37.518
activation of precursors.

676
00:57:39.079 –> 00:57:44.088
Okay, thank you. Given the strong conservation of the adipose organ’s anatomy,

677
00:57:44.478 –> 00:57:47.808
which current in vitro models come closest to it?

678
00:57:48.018 –> 00:57:53.898
Organoids, spheroids, co-culture, organ chip, and what do they miss most?

679
00:57:54.829 –> 00:58:00.258
This is the first question. Then also, while studying obesity associated muscle D,

680
00:58:00.768 –> 00:58:06.108
should models of adipose-liver crosstalk include adipose plasticity, for instance,

681
00:58:06.228 –> 00:58:11.808
by using brown versus inflamed adipocytes as the source of secreted factors?

682
00:58:13.188 –> 00:58:18.498
Regarding the first question, it depends on what you want to see, of course.

683
00:58:20.209 –> 00:58:25.728
Some aspects are more visible when you have a normal culture

684
00:58:26.239 –> 00:58:29.239
system. Some other aspects when you have a

685
00:58:32.628 –> 00:58:33.079
3D

686
00:58:34.368 –> 00:58:40.188
system, explant, et cetera. It depends from what is the main question you

687
00:58:40.248 –> 00:58:41.058
want to answer.

688
00:58:43.068 –> 00:58:44.418
The second question is?

689
00:58:46.489 –> 00:58:52.008
So if obesity associated with muscle D, should models of

690
00:58:52.098 –> 00:58:57.978
adipose-liver crosstalk include adipose plasticity, and use

691
00:58:58.068 –> 00:59:03.648
brown adipose tissue versus inflamed adipose tissue in these crosstalk

692
00:59:03.709 –> 00:59:04.248
models?

693
00:59:05.778 –> 00:59:11.058
In the crosstalk models, I think that the main factor is

694
00:59:11.568 –> 00:59:16.489
the situation of visceral adipose tissue.

695
00:59:16.968 –> 00:59:22.429
The crosstalk is mainly with the visceral, and the situation of

696
00:59:22.548 –> 00:59:28.218
inflammation and fibrosis of this tissue can influence, of course, this

697
00:59:28.368 –> 00:59:29.088
crosstalk.

698
00:59:30.498 –> 00:59:32.568
Okay, I’m going to ask you the last question.

699
00:59:32.628 –> 00:59:36.949
I’m sorry for all the questions that remains unanswered because there are plenty of

700
00:59:37.008 –> 00:59:41.538
those, but Professor Cinti’s email address is in the presentation, and the

701
00:59:41.568 –> 00:59:44.838
presentation is recorded, so you can contact him.

702
00:59:44.929 –> 00:59:47.598
I’m sure he’s going to be very happy to answer your question.

703
00:59:47.628 –> 00:59:52.758
He loves staying with students and having inputs from young, so I can assure that.

704
00:59:52.848 –> 00:59:58.579
So last question. When we work in vitro with white adipocytes, they do not develop

705
00:59:58.638 –> 01:00:04.218
a single giant lipid droplet after differentiation, but instead they

706
01:00:04.278 –> 01:00:09.648
develop multiple small lipid droplets, similar to the brown adipose tissue.

707
01:00:10.218 –> 01:00:12.378
Why is this? This is the question.

708
01:00:12.768 –> 01:00:14.748
Which kind of adipocyte?

709
01:00:14.838 –> 01:00:19.398
When you study adipocytes in vitro and you differentiate them into mature

710
01:00:19.459 –> 01:00:22.848
adipocytes, you don’t get to have a big adipocyte with a huge-

711
01:00:22.968 –> 01:00:28.758
Oh, yeah. This is just a technical problem, because if you make

712
01:00:28.878 –> 01:00:32.868
a cultivation with the reverse of the–

713
01:00:34.398 –> 01:00:39.018
Because with the unilocular adipocyte,

714
01:00:39.558 –> 01:00:45.228
detach from the bottom, and so you lose the

715
01:00:45.679 –> 01:00:48.618
unilocular adipocyte. But there was a

716
01:00:51.768 –> 01:00:52.459
japonais

717
01:00:53.838 –> 01:00:56.718
researcher that invented the reverse

718
01:00:58.068 –> 01:01:03.949
kind of culture system in which you can obtain a unilocular

719
01:01:04.038 –> 01:01:07.308
adipocyte. It’s only a technical problem.

720
01:01:08.449 –> 01:01:10.128
So with that, we’re going to-

721
01:01:10.459 –> 01:01:12.739
May I add one single thing?

722
01:01:13.518 –> 01:01:14.598
D'accord.

723
01:01:14.688 –> 01:01:18.588
My book is available for

724
01:01:19.938 –> 01:01:25.818
all of you for free. Just ask me the book, I will send.

725
01:01:26.929 –> 01:01:31.308
Okay. Yes. So thank you very much. I remind everybody that Professor Cinti is

726
01:01:31.368 –> 01:01:36.888
professor of human anatomy. So these images, this approach, microscopic approach

727
01:01:36.949 –> 01:01:42.498
that has been his strength in his career derives also from the view of the human

728
01:01:42.558 –> 01:01:45.829
anatomy as his teaching area. Okay.

729
01:01:46.429 –> 01:01:50.388
So again, thank you very much, Professor Cinti, for this beautiful presentation.

730
01:01:50.449 –> 01:01:50.959
Merci.

731
01:01:50.959 –> 01:01:55.098
And thanks to everybody for joining and asking so many questions and stay

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01:01:56.508 –> 01:02:01.338
up to the end of the presentation. We hope to see you during the next webinar

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series. And thank you, Emil, and professor again, and everybody.

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Have a good evening.