Fenofibrate Prevents Weight Gain in DIO Mice Independent of Subcutaneous White Adipose Tissue Browning

Activation of peroxisome proliferator activated receptor alpha (PPARα) affects energy metabolism in adipocytes. Our group and others have shown fenofibrate, a PPARα agonist, increases energy expenditure and prevents weight gain in diet‐induced obese mice. The aim of this study is to evaluate if fenofibrate‐induced weight loss is a consequence of subcutaneous white adipose tissue browning. Male C57BL/6 mice at 8 weeks' old (n ± 40; CEUA 165/2011) were randomly assigned to receive a control (CD) or a high‐fat diet (HFD) for 6 weeks. After that, they were subdivided into four groups: C group (fed with CD, untreated), CF group (fed with CD and treated with fenofibrate), H group (fed with HFD, untreated) and HF group (fed with HFD and treated with fenofibrate). Fenofibrate (50 mg/Kg/day) was administered daily by oral gavage for 2 weeks. After 48h of the last dose, they were euthanized. Expression of mRNAs ( Ucp1 , Elovl3 and Eva‐1 ) in inguinal adipose tissue were measured by Real‐time PCR assay. Mice fed with HFD showed augment of body weight gain, visceral fat depots weights, fasting leptin and insulin serum levels and reduced constant of glucose disappearance (Kitt). Without changes in food intake, fenofibrate treatment attenuated the weight gain in both CF and HF groups, contributing to reduce the adipose tissue storage, and restored insulin and leptin levels when compared to C group. Kitt was not different between HF and H groups. Expression of Ucp1, Elovl3 and Eva‐1 were down regulated in obese mice and fenofibrate had no effect on their expression. On the other hand, in control mice, fenofibrate increased Eva‐1 expression, a gene characteristic of classical murine brown fat. In conclusion, fenofibrate prevents weight gain in obese mice by a mechanism that seems not to involve subcutaneous white adipose tissue browning. Support or Funding Information FAPESP and CAPES This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .