Effect of osteocalcin on sarcopenic obesity

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09521
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Kyushu University
• Principal Investigator: Mizokami Akiko 九州大学, 歯学研究院, 准教授 (70722487)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: オステオカルシン / 脂肪分解 / 肥満

Outline of Final Research Achievements

Uncarboxylated osteocalcin (GluOC) is a bone-derived hormone that plays an important role not only in glucose and energy metabolism but also in maintaining skeletal muscle mass. GPRC6A, a member of family C of G protein-coupled receptors, has been reported to serve as a GluOC receptor. We analyzed adipocyte-specific GPRC6A deficient mice and found that these animals manifested adipocyte hypertrophy under obesogenic environment. This was associated with reduced lipolytic activity due to down-regulation of lipolytic enzymes in adipose tissue of the knockout mice. Suppressed lipolysis resulted in reduced fatty acid release in the circulation compared with control mice. Our results suggest that the constitutive activation of GPRC6A signaling by GluOC in adipocytes plays a key role in lipolysis, providing fatty acid as an energy source to the skeletal muscle.

Free Research Field

基礎歯学

Academic Significance and Societal Importance of the Research Achievements

サルコペニア肥満は、代謝異常と運動機能低下の悪循環によって、サルコペニアや肥満の単独事象よりも深刻な身体機能低下をもたらし、要介護・寝たきりのリスクが高まる。GluOCは、脂肪細胞におけるGPRC6Aシグナルを介して脂肪の分解を促進する。つまり、GluOCは食餌誘発性の肥満とそれに起因する代謝異常を抑制するのみならず、脂肪分解促進作用による遊離脂肪酸放出によって骨格筋にエネルギー源を供給し、骨格筋の機能向上にも寄与する。GluOCはサルコペニアと肥満の両方にアプローチすることでサルコペニア肥満の悪循環を断ち切る治療標的となり得る。