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

By P. Cohen, J. D. Levy, Yingying Zhang, A. Frontini, D. Kolodin, Katrin J. Svensson, James C. Lo, Xing Zeng, L. Ye, M. Khandekar and 12 more. Cell, 2014

851 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/aac8cb497da004072f140f6c57c8bf9cb9473047

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. J. Hawley
2. B. Spiegelman

In Epidemiology

1. B. Spiegelman
2. S. Kajimura
3. P. Seale
4. Jamal Naderi
5. M. Longo
6. C. Miele
7. G. A. Raciti
8. F. Beguinot

In Physiology

1. S. Kajimura
2. P. Seale
3. B. Spiegelman
4. J. Hawley
5. Jamal Naderi
6. M. Longo
7. C. Miele
8. Steven P. Gygi

Citations in the corpus

• Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (2014, background): “…5Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 2AJ, UK 6Ember Therapeutics, Inc., 480 Arsenal Street, Building 1, Suite 101, Watertown, MA 02472, USA *Correspondence: bruce_spiegelman@dfci.harvard.edu http://dx.doi.org/10.1016/j.cell.2014.03.065”
• Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications (2019, background): “, dendritic cells, mast cells, neutrophils, B cells, and T cells) reside in adipose tissue during obesity, playing a key role in the development of inflammation and IR [103,110].”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Intriguingly, PRDM16 expression in white adipocytes not only activates the brown fat-selective gene program but also represses the white fat- or muscle-selective gene program (Kajimura et al., 2008; Seale et al., 2007, 2008).”
• Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders (2016, background): “Second, even though PRD1-BF-RIZ1 homologous domain-containing protein-16 (PRDM16) has been recognized as a critical transcriptional coactivator for both brown and beige adipocytes, PRDM16 depletion impedes beige adipocyte development upon β-adrenergic stimulation but has no effect on brown adipocyte”