Mechanisms of interaction between age-dependent obesity and localization of melanocoretin-4 receptors

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K15571
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Nagoya University
• Principal Investigator: Oya Manami 名古屋大学, 医学系研究科, 学振特別研究員(RPD) (90777997)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: メラノコルチン / 生理学 / 肥満 / 加齢 / 代謝調節 / 摂食制御

Outline of Final Research Achievements

Obesity is often developed with age due to attenuation of energy expenditure including metabolic thermogenesis. However, the mechanism of age-dependent attenuation of whole-body metabolism is unknown. In this study, we focused on melanocortin-4 receptors (MC4Rs), which play essential roles in the regulation of the central neural circuit controlling metabolic thermogenesis in brown adipose tissue (BAT). Our in vivo physiological experiments revealed that skin cooling-induced BAT thermogenesis and MC4R agonist-induced BAT thermogenesis were attenuated in older (6 months old) male rats compared with younger (9 weeks old) ones. To elucidate the mechanism of the age-dependent attenuation of MC4R sensitivity to melanocortin signals, we examined the distribution of MC4Rs. We found that aging changes the localization of MC4Rs. Thus, we hypothesized that age-dependent alteration in the localization of MC4R induces attenuation of MC4R sensitivity in older animals.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

飽食と高齢化が進む現代において、加齢による肥満の発症機構の解明は重要な課題である。加齢性肥満の発症の原因の一つとして代謝量の減少が考えられるが、加齢による代謝量の低下メカニズムは明らかにされていない。本研究によってMC4Rを介した摂食・代謝調節機構が加齢によって変化するメカニズムを分子レベルで解明することが出来れば、これまでに考えられていなかった新しい肥満発症機構の提示につながるだけでなく、MC4Rの局在の制御を通じた画期的な肥満予防法や治療法の開発に寄与できると考える。