Orexin is a brain hormone that rises in the morning to make us wakeful. A new study shows that higher levels of orexin in the blood during morning hours is linked to better health; levels of orexin tend to decrease with obesity. Where does orexin function outside of the brain? Researchers suggest it may be held in adipose (fat) tissue: higher levels of the receptor to this hormone also signify better metabolic health, including insulin sensitivity and blood lipids. People with obesity who demonstrate a higher capacity of adipose tissue to respond to orexin in the morning may be metabolically healthier than those whose adipose tissue exhibits diminished ability to sense orexin.
The potential for human adipose tissue to respond to the neuropeptide hormone orexin during morning hours is decreased in people with obesity, but greater response capacity defines persons with improved metabolic phenotype even beyond BMI
A new cross-sectional study from Japan and Israel investigated whether human adipose tissue could be a direct target of orexin/hypocretin, and the impact of obesity. Orexin is a neuropeptide that acts in the brain as a central regulator of the sleep/wake cycle. Defects in orexin/orexin-receptor system are known to cause serious disturbances in the wakeful state, including narcolepsy. Intriguingly, sleeping disorders commonly affect persons with obesity, and new medications based on the orexin/orexin-receptor system are being developed to treat sleeping disorders. Evidence from animal models suggest metabolic effects of orexin-based pharmaceuticals.
The bi-national research team studied blood and adipose tissue samples collected during morning hours (when orexin’s activity should be high), of n=81 participants who were without obesity, with obesity, or obesity and type 2 diabetes. Morning circulating blood levels of orexin tended to be lower with increasing BMI, and higher levels associated with improved insulin sensitivity and lipid profile. Intriguingly, in a minority of participants, orexin was expressed at the mRNA level in adipose tissue, and these participants exhibited a more favorable metabolic profile compared to the majority who did not express orexin in their adipose tissue. Among the two orexin receptors only the receptor type 1 could be detected in human adipose tissue. Its levels were lower in participants with obesity or obesity and type 2 diabetes compared to participants without obesity. Higher expression level of Orexin receptor 1 in either subcutaneous and visceral adipose tissue correlated with improved insulin sensitivity and lipid profile, even beyond the association with BMI.
In conclusion, human adipose tissues bear the capacity to respond to orexin – a neuropeptide best known to act in the brain and regulate the sleep/wake cycle. Outside the brain – it seems to regulate metabolism and adopt it to the wakeful (=feeding) state. Obesity seems to diminish the capacity of adipose tissue to respond to morning levels of orexin. However, higher expression of orexin receptor in human adipose tissue, and higher morning orexin levels in the blood, define persons with improve insulin sensitivity and lipid profile.
This study was supported by a joint program of the Israel Science Foundation, and by the Japan Society for the Promotion of Science.
Link to pub-med: https://pubmed.ncbi.nlm.nih.gov/34472713/