OR23-4 Turning White Fat Brown - Can a Metabolic Villain be Reformed?

Program: Abstracts - Orals, Poster Previews, and Posters
Session: OR23-Thyroid Hormone Action, Cancer and Clinical Thyroid
Friday, March 6, 2015: 11:30 AM-1:00 PM
Presentation Start Time: 12:15 PM
Room 6B (San Diego Convention Center)
Kevin Phillips
Houston Methodist Research Institute, Houston, TX
Mammals possess both white (WAT) and brown adipose tissue (BAT). WAT has low metabolic potential and is associated with obesity and the maladies of metabolic syndrome, while BAT has high metabolic potential and is associated with resistance to obesity. Functional conversion of WAT into a tissue with BAT-like activity, an action often referred to as “browning” has become an intriguing strategy to combat metabolic disease. Although, thyroid hormone receptors (TRs) have long been associated with metabolic regulation and adaptive thermogenesis, a full understanding of this relationship is lacking. Here, we report that pharmacological TR activation the synthetic agonist GC-1 evokes a profound functional conversion of WAT into a brown adipose-like tissue. TR agonist treatment of genetically obese (ob/ob) and diet induced obese (DIO) mice dramatically increases UCP-1 expression and upregulates the entire program of adaptive thermogenesis, uncoupled respiration, and mitochondrial biogenesis in WAT that is correspondent with an amelioration of obesity and insulin resistance. Consistent with the idea that metabolic increase is mediated principally by WAT, this effect does not require functional brown fat, yet all thermogenesis is lost in lean mice that possess little WAT. TR activation can also induce uncoupled respiration in white adipocytes in vitro demonstrating that browning is a cell autonomous effect of TR activation in WAT. This data demonstrates that TR activation can elicit a functional conversion of white to brown fat, a previously unrecognized component of TR-mediated thermogenesis, and suggests that WAT browning may have profound pharmacological potential.

Nothing to Disclose: KP

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