Details

Autor(en) / Beteiligte

• 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.

Titel

Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch

Ist Teil von

• Cell, 2014-01, Vol.156 (1-2), p.304-316

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Adipocyte-specific deletion of PRDM16 inhibits beige adipocyte function•Mutant animals develop dietary obesity, insulin resistance, and hepatic steatosis•Mutant subcutaneous fat acquires cellular and molecular properties of visceral fat•PRDM16 may determine key differences between subcutaneous and visceral fat Loss of PRDM16 inhibits beige adipocyte function and leads to the visceralization of fat.