Efeitos da ativação do PPAR-alfa no remodelamento do tecido adiposo marrom de camundongos alimentados com dieta rica em lipídio ou frutose

Abstract

This work aimed to analyze the effects of a selective PPAR-alpha agonist on the adverse remodeling of brown adipose tissue (TAM) (whitening) in mice fed a high fat or high fructose diet, with emphasis on thermogenesis, beta-oxidation and lipolysis. Fifty animals were randomly assigned to receive a control diet (C, 10% lipid as energy), hyperlipid diet (HF, 50% lipid as energy) or high fructose diet (HFRU, 50% fructose as energy). 12 weeks The HF and HFRU groups were redivided to initiate 5-week treatment: C, HF, HF-a, HFRU and HFRU-a. The PPAR-alpha agonist (WY14643) was mixed with the diet at a dose of 3.5 mg/kg body mass (BM). The following analyses were performed: BM, food intake, OGTT, indirect calorimetry, termography, light and confocal microscopy, plasma analyses and q-PCR. The HF group had overweight, while the HF and HFRU groups presented oral glucose intolerance and metabolic alterations, which were attenuated by PPARα activation. The HF and HFRU groups showed reduced immunostaining of UCP1 and VEGFA, but only the HF group showed a pattern of lipid droplet accumulation that resembled white adipose tissue (TAB), characterizing whitening. Whitening in the HF group was accompanied by decreased expression of genes related to thermogenesis, β-oxidation and lipolysis. All of these were increased by PPARα activation. The treated groups also showed a lower respiratory exchange rate than the untreated groups, suggesting that lipids were used as fuel for thermogenesis. In conclusion, the PPARα agonist reversed the interscapular TAM (TAMi) whitening and attenuated the histological changes in the HFRU group, inducing the thermogenic pathway, reducing the size of lipid droplets, and increasing the adrenergic stimulus and lipolysis in the treated HF group.