RGD Reference Report - Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. - Rat Genome Database

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Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch.

Authors: Cohen, Paul  Levy, Julia D  Zhang, Yingying  Frontini, Andrea  Kolodin, Dmitriy P  Svensson, Katrin J  Lo, James C  Zeng, Xing  Ye, Li  Khandekar, Melin J  Wu, Jun  Gunawardana, Subhadra C  Banks, Alexander S  Camporez, João Paulo G  Jurczak, Michael J  Kajimura, Shingo  Piston, David W  Mathis, Diane  Cinti, Saverio  Shulman, Gerald I  Seale, Patrick  Spiegelman, Bruce M 
Citation: Cohen P, etal., Cell. 2014 Jan 16;156(1-2):304-16. doi: 10.1016/j.cell.2013.12.021.
RGD ID: 13673820
Pubmed: PMID:24439384   (View Abstract at PubMed)
PMCID: PMC3922400   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2013.12.021   (Journal Full-text)

A clear relationship exists between visceral obesity and type 2 diabetes, whereas subcutaneous obesity is comparatively benign. Here, we show that adipocyte-specific deletion of the coregulatory protein PRDM16 caused minimal effects on classical brown fat but markedly inhibited beige adipocyte function in subcutaneous fat following cold exposure or ß3-agonist treatment. These animals developed obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They also showed altered fat distribution with markedly increased subcutaneous adiposity. Subcutaneous adipose tissue in mutant mice acquired many key properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation. Transplantation of subcutaneous fat into mice with diet-induced obesity showed a loss of metabolic benefit when tissues were derived from PRDM16 mutant animals. These findings indicate that PRDM16 and beige adipocytes are required for the "browning" of white fat and the healthful effects of subcutaneous adipose tissue.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Prdm16Ratpositive regulation of cold-induced thermogenesis involved_inISSUniProtKB:A2A935PMID:24439384YuBioLab 

Objects Annotated

Genes (Rattus norvegicus)
Prdm16  (PR/SET domain 16)

Additional Information