Analysis of the regulation of energy matabolism in skeletal muscle by PGC1alpha

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04848
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: Ogawa Wataru 神戸大学, 医学研究科, 教授 (40294219)
• Co-Investigator(Renkei-kenkyūsha): NOMURA Kazuhiro 神戸大学, 医学部附属病院, 医員 (70450236)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 骨格筋 / エネルギー代謝 / 肥満

Outline of Final Research Achievements

We have identified novel isoforms of the transcriptional coactivator PGC-1alpha which expression is robustly upregulated in skeletal muscle in response to exercise. Mice that lack the novel isoforms of PGC-1 -alpha develop obesity due to the decreased energy expenditure during exercise and are not able to maintain their body temperature on exposure to cold circumstance. We have found that beta-adrenergic stimulus plays an important role in the upregulation of the PGC-1alpha isoforms in skeletal muscle during exercise. In obese mice models or in aged mice, exercise-induced upregulation of the PGC1alpha isoforms is impaired, which is attributable to the decrease in the sensitivity of skeletal muscle to the PGC-1alpha isoforms. Whereas the expression of the transcription factor KLF15 is regulated by the PGC1-alpha isoforms, the downstream pathway of PGC-1-alpha isoforms that lead to the regulation of energy metabolism during exercise is independent of KLF15.

Free Research Field

代謝学