Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch
| Autor: | David W. Piston, Subhadra C. Gunawardana, Julia D. Levy, Michael J. Jurczak, Joao Paulo Camporez, Bruce M. Spiegelman, Andrea Frontini, Paul Cohen, Melin J. Khandekar, Saverio Cinti, Yingying Zhang, Patrick Seale, Xing Zeng, Katrin J. Svensson, Li Ye, Alexander S. Banks, Dmitriy Kolodin, Gerald I. Shulman, Shingo Kajimura, Diane Mathis, James C. Lo, Jun Wu |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Adipose tissue 030209 endocrinology & metabolism Type 2 diabetes White adipose tissue Biology Diet High-Fat General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance Adipose Tissue Brown Internal medicine medicine Adipocytes Animals Obesity 030304 developmental biology 2. Zero hunger PRDM16 Mice Knockout 0303 health sciences Biochemistry Genetics and Molecular Biology(all) medicine.disease Transplantation DNA-Binding Proteins Endocrinology Adipose Tissue Steatosis Insulin Resistance Transcription Factors |
| Zdroj: | Cell. 156(1-2) |
| ISSN: | 1097-4172 |
| Popis: | SummaryA 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. |
| Databáze: | OpenAIRE |
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