Elucidation of functional significance of PPAR gamma on energy metabolism using PPAR gamma mutant rats.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461335
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The Tazuke Kofukai (2016); Kyoto University (2014-2015)
• Principal Investigator: AIZAWA-ABE Megumi 公益財団法人田附興風会, 医学研究所 第3研究部, 研究員 (20568688)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: PPARγ / ラットモデル / 糖代謝 / 脂肪細胞分化 / 種差

Outline of Final Research Achievements

Agonist-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) stimulates adipocyte differentiation and insulin sensitivity. In the context of the interspecies intranslatability of PPARγ-related findings, we generated a PPARγ mutant rat with a loss-of-function mutation. Heterozygous rats showed reduced fat mass with adipocyte hypertrophy and insulin resistance, which were highly predictable from known actions of PPARγ agonists and phenotypes of patients with the PPARγ mutation. We demonstrate that both alleles of PPARγ are required for normal adipocyte development and insulin sensitivity in vivo. Furthermore, the study indicates that PPARγ regulates mainly adipocyte number rather than adipocyte size in vivo. The choice of appropriate species as experimental models is critical, especially for the study of PPARγ.

Free Research Field

代謝