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.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
F344-Ppargm1KyoRatabnormal fat cell differentiation  IAGP  RGD 
PpargRatabnormal fat cell differentiation  IAGP  RGD 
Ppargm1KyoRatabnormal fat cell differentiation  IAGP  RGD 
F344-Ppargm1KyoRatdecreased epididymal fat pad weight  IAGP  RGD 
PpargRatdecreased epididymal fat pad weight  IAGP  RGD 
Ppargm1KyoRatdecreased epididymal fat pad weight  IAGP  RGD 
F344-Ppargm1KyoRatdecreased total fat pad weight inducesIAGPstandard dietcompared to wild type ratsRGD 
PpargRatdecreased total fat pad weight inducesIAGPstandard dietcompared to wild type ratsRGD 
Ppargm1KyoRatdecreased total fat pad weight inducesIAGPstandard dietcompared to wild type ratsRGD 
F344-Ppargm1KyoRatimpaired glucose tolerance  IAGP compared to wild type ratsRGD 
PpargRatimpaired glucose tolerance  IAGP compared to wild type ratsRGD 
Ppargm1KyoRatimpaired glucose tolerance  IAGP compared to wild type ratsRGD 
F344-Ppargm1KyoRatincreased fat cell size  IAGP  RGD 
PpargRatincreased fat cell size  IAGP  RGD 
Ppargm1KyoRatincreased fat cell size  IAGP  RGD 
F344-Ppargm1KyoRatincreased liver triglyceride level  IAGP  RGD 
PpargRatincreased liver triglyceride level  IAGP  RGD 
Ppargm1KyoRatincreased liver triglyceride level  IAGP  RGD 
F344-Ppargm1KyoRatincreased liver weight inducesIAGPcontrolled fat content diet RGD 
PpargRatincreased liver weight inducesIAGPcontrolled fat content diet RGD 
Ppargm1KyoRatincreased liver weight inducesIAGPcontrolled fat content diet RGD 
F344-Ppargm1KyoRatincreased skeletal muscle weight inducesIAGPcontrolled fat content diet RGD 
PpargRatincreased skeletal muscle weight inducesIAGPcontrolled fat content diet RGD 
Ppargm1KyoRatincreased skeletal muscle weight inducesIAGPcontrolled fat content diet RGD 
F344-Ppargm1KyoRatinsulin resistance inducesIAGPcontrolled fat content dietcompared to wild type ratsRGD 
PpargRatinsulin resistance inducesIAGPcontrolled fat content dietcompared to wild type ratsRGD 
Ppargm1KyoRatinsulin resistance inducesIAGPcontrolled fat content dietcompared to wild type ratsRGD 
Objects Annotated

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

Strains
F344-Ppargm1Kyo  (NA)


Additional Information