ECO2023 NEWSLETTER: DAY FOUR – EASO-Novo Nordisk Foundation Obesity Prize for Excellence – Ruth Loos

ECO2023 NEWSLETTER: DAY FOUR – EASO-Novo Nordisk Foundation Obesity Prize for Excellence – Ruth Loos

For more info on the awards and prizes, click here

Due to family commitments we were unable to interview Ruth! However, here is a brief synopsis of her work.

Ruth is based University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Researchwhere she is vice executive director, professor, and group leader.

Her research focuses on the identification of genes associated with obesity to gain insight into the biology that underlies body weight regulation. She contributed to the discovery of the first obesity locus, FTO (Science 2007) and led the work that identified the second locus, near MC4R, showing that common variants in a monogenic gene affect body weight in the general population (Nat Genet 2008). She continued her gene discovery work, leading the obesity workgroup in the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, identifying >1,500 BMI-associated loci. Enrichment analyses based on the genes in identified loci have pointed to the brain as a critical player in body weight regulation, consistent with models of extreme obesity. These discoveries have been reported in five seminal papers, published in Nature and Nature Genetics, with Dr. Loos as lead author.

Acknowledging that obesity is a heterogenous condition, Ruth pioneered gene discovery for refined adiposity traits to target deeper layers of the biology that define obesity. Gene discovery for body fat identified loci distinct from those for BMI, pointing to adipocyte, lipid and glycemic metabolism (Natu Genet 2011; Nat Commun 2017). Gene discovery for circulating leptin levels identified eight novel loci that, in functional follow-up analyses, pointed to new actionable targets (Nat Commun 2016, Nat Med 2019, Diabetes 2020). In another approach, Ruth created composite phenotypes that represent adiposity and cardiometabolic traits in one analysis. The 62 loci identified represent mechanisms that uncouple adiposity from its comorbidities, including adipocyte differentiation, fat distribution, insulin signaling, inflammation and fatty acid oxidation (Nat Metab 2021).

Besides gene discovery, Ruth uses epidemiological methods to assess the role of genetics in precision medicine. Using this approach, she showed that healthy lifestyles can attenuate genetic susceptibility to weight gain by 30–40% (PLoS Med 2010 & 2011, PLoS Genet 2017, Nat Commun 2017). In recent work, she integrates genes and environment to improve obesity prediction. Furthermore, she uses advanced statistical approaches to identify association signatures across multiple adiposity traits that allow for population subtyping (Nat Metab 2021), which is key in precision health to tailor prevention and treatment strategies and improve disease prediction and prognosis.

For more on Ruth’s research team, click here