@article{170a537b54e5451995cb0b567ce42e01,
title = "Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch",
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.",
author = "Paul Cohen and Levy, {Julia D.} and Yingying Zhang and Andrea Frontini and Kolodin, {Dmitriy P.} and Svensson, {Katrin J.} and Lo, {James C.} and Xing Zeng and Li Ye and Khandekar, {Melin J.} and Jun Wu and Gunawardana, {Subhadra C.} and Banks, {Alexander S.} and Camporez, {Jo{\~a}o Paulo G.} and Jurczak, {Michael J.} and Shingo Kajimura and Piston, {David W.} and Diane Mathis and Saverio Cinti and Shulman, {Gerald I.} and Patrick Seale and Spiegelman, {Bruce M.}",
note = "Funding Information: We thank Dr. Evan Rosen (Beth Israel Deaconess Medical Center) for providing Adiponectin-Cre mice, Dr. Vicki Huff (MD Anderson) for providing Wt1 lox/lox mice, and the Nikon Imaging Center at Harvard Medical School for use of microscopy equipment. We thank Dr. Vamsi Mootha (Massachusetts General Hospital) for guidance on data analysis and Drs. Rana Gupta, Pere Puigserver, Evan Rosen, and members of the Spiegelman lab for helpful discussions. P.C. was supported by the American Heart Association grant 11FTF7510004. D.P.K. was supported by a National Science Foundation Graduate Research Fellowship. This work was supported by NIH grants DK040936, DK045735, DK059635 (G.I.S.); NIH grant DK092541 (D.M.); and by NIH grant DK031405 and the JPB foundation (B.M.S.). ",
year = "2014",
doi = "10.1016/j.cell.2013.12.021",
language = "English",
volume = "156",
pages = "304--316",
journal = "Cell",
issn = "0092-8674",
number = "1-2",
}