RGD Reference Report - Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPARĪ³ Mutant Rats. - Rat Genome Database

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Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPARĪ³ Mutant Rats.

Authors: Gumbilai, Valentino  Ebihara, Ken  Aizawa-Abe, Megumi  Ebihara, Chihiro  Zhao, Mingming  Yamamoto, Yuji  Mashimo, Tomoji  Hosoda, Kiminori  Serikawa, Tadao  Nakao, Kazuwa 
Citation: Gumbilai V, etal., Diabetes. 2016 Oct;65(10):2954-65. doi: 10.2337/db15-1422. Epub 2016 Jul 5.
RGD ID: 127285618
Pubmed: PMID:27381370   (View Abstract at PubMed)
DOI: DOI:10.2337/db15-1422   (Journal Full-text)

Agonist-induced activation of peroxisome proliferator-activated receptor-γ (PPARγ) stimulates adipocyte differentiation and insulin sensitivity. Patients with heterozygous PPARγ dominant-negative mutation develop partial lipodystrophy and insulin resistance. Inconsistent with this evidence in humans, it was reported that heterozygous PPARγ knockout mice have increased insulin sensitivity and that mice with heterozygous PPARγ dominant-negative mutation have normal insulin sensitivity and improved glucose tolerance. In the context of the interspecies intranslatability of PPARγ-related findings, we generated a PPARγ mutant rat with a loss-of-function mutation (Pparg(mkyo)) without dominant-negative activity by using the ENU (N-ethyl-N-nitrosourea) mutagenesis method. Heterozygous Pparg(mkyo/+) 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. This report is the first in our knowledge to clearly 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.

Objects Annotated

Genes (Rattus norvegicus)
Pparg  (peroxisome proliferator-activated receptor gamma)
Ppargm1Kyo  (peroxisome proliferator-activated receptor gamma; ENU induced mutant 1, Kyo)

F344-Ppargm1Kyo  (NA)

Additional Information