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

Paul Cohen, Julia D. Levy, Yingying Zhang, Andrea Frontini, Dmitriy P. Kolodin, Katrin J. Svensson, James C. Lo, Xing Zeng, Li Ye, Melin J. Khandekar, Jun Wu, Subhadra C. Gunawardana, Alexander S. Banks, João Paulo G. Camporez, Michael J. Jurczak, Shingo Kajimura, David W. Piston, Diane Mathis, Saverio Cinti, Gerald I. ShulmanPatrick Seale, Bruce M. Spiegelman

Research output: Contribution to journalArticlepeer-review

667 Scopus citations

Abstract

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 β3-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.

Original languageEnglish (US)
Pages (from-to)304-316
Number of pages13
JournalCell
Volume156
Issue number1-2
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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