Editors' ChoiceObesity

TRIPpin’ on a Fat Cell

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Science Translational Medicine  13 Feb 2013:
Vol. 5, Issue 172, pp. 172ec27
DOI: 10.1126/scitranslmed.3005829

You’ve heard the news—the world is growing fatter every year. Although the detrimental effects of the obesity epidemic are unquestionable, pharmaceutical treatments for it remain plagued by serious and uncomfortable side effects, including gastrointestinal distress and cardiotoxicity. Surgical options for obesity, including gastric bypass surgery, are effective but carry with them inherent risks, making them practical only in severe cases. Now, a study by Liew et al. has identified a new role for the transcriptional coregulator TRIP-Br2 in controlling metabolism and diet-induced obesity that may pave the way for new treatments for obesity.

White adipose tissue is a major energy reserve in humans; its rate of cellular metabolism is controlled through an intricate regulation of gene expression by transcription factors and coregulatory molecules. Coregulators can act as positive or negative mediators of gene transcription. These factors act in concert to control fat storage primarily through peroxisome proliferation-activated receptor-γ (PPAR-γ)—the master regulator of metabolism. Liew and colleagues created a mouse that lacked the expression of TRIP-Br2, a transcriptional coregulator whose role in adipose tissue was unknown. They found that mice lacking TRIP-Br2 gained about half of the weight and visceral fat as did control mice when given a high-fat diet for 18 weeks. In addition, the fat cells in TRIP-Br2–null mice had an increased rate of fat metabolism, decreased size, and lower amounts of inflammatory factors. The researchers also examined the expression of TRIP-Br2 in the visceral fat of human patients and found significantly higher expression of TRIP-Br2 in obese patients as well as a strong association of its expression with markers of diabetes.

The work of Liew et al. identifies the role of TRIP-Br2 in regulating obesity and metabolism in mice and demonstrates that TRIP-Br2 expression is strongly associated with sequelae of obesity in human patients. Their work is a major step forward in identifying therapeutic targets that modulate metabolism to fight obesity rather than targeting other mechanisms such as inhibiting hunger or blocking digestive pathways. Further studies are needed to identify safe and efficacious inhibitors for TRIP-Br2 in order to translate these findings into clinical practice.

C. W. Liew et al., Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nat. Med. 19, 217–226 (2013). [PubMed]

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