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

Paul Cohen1, Julia D Levy2, Yingying Zhang2

  • 1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

Cell
|January 21, 2014
PubMed

Insights

The coregulatory protein PRDM16 is essential for beige adipocyte function, which protects against obesity and insulin resistance. Loss of PRDM16 converts beneficial subcutaneous fat into harmful visceral fat.

Area of Science:

  • Metabolic disease
  • Adipose tissue biology
  • Obesity research

Background:

  • Visceral obesity is strongly linked to type 2 diabetes, while subcutaneous obesity is generally considered less harmful.
  • The role of specific proteins in regulating fat tissue function and metabolic health is an area of active investigation.

Purpose of the Study:

  • To investigate the function of the coregulatory protein PRDM16 in adipocytes.
  • To determine the impact of PRDM16 deletion on beige adipocyte activity and overall metabolic health.

Main Methods:

  • Generated mice with adipocyte-specific deletion of PRDM16.
  • Administered cold exposure and beta-3 adrenergic agonist to stimulate beige adipocyte function.
  • Assessed metabolic parameters including obesity, insulin resistance, and hepatic steatosis on a high-fat diet.
  • Performed fat tissue transplantation experiments.

Main Results:

  • PRDM16 deletion inhibited beige adipocyte function in subcutaneous fat but had minimal effects on classical brown fat.
  • Mice lacking PRDM16 in adipocytes developed obesity, severe insulin resistance, and hepatic steatosis when fed a high-fat diet.
  • Subcutaneous adipose tissue in mutant mice exhibited visceral fat characteristics, including altered gene expression and increased macrophage accumulation.
  • Transplantation of subcutaneous fat from PRDM16 mutant mice failed to provide metabolic benefits.

Conclusions:

  • PRDM16 is crucial for the "browning" of white adipose tissue and the beneficial metabolic effects of subcutaneous fat.
  • Beige adipocytes, regulated by PRDM16, play a vital role in maintaining metabolic health and preventing obesity-related diseases.

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