Background and aimsObesity compromises adipocyte physiology. PPARs are essential to adipocyte plasticity, but its isolated role in the browning phenomenon is not clear. This study aimed to examine whether activation of PPAR-α or PPAR-β/δ could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice.Material and methodsSixty animals were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for ten weeks. Then each group was re-divided to begin the treatments that lasted 4 weeks, totalizing six groups: C, C-α (C plus PPAR-α agonist, 2.5 mg/kg BM), C-β (C plus PPAR-β/δ agonist, 1 mg/kg BM), HF, HF-α (HF plus PPAR-α agonist), HF-β (HF plus PPAR-β/δ agonist).ResultsHF animals presented with overweight, glucose intolerance and subcutaneous white adipocyte hypertrophy. Both treatments significantly attenuated these parameters. Browning, verified by UCP1 positive beige cells and enhanced body temperature, was just observed in PPAR-α treated groups. PPAR-α agonism also elicited an enhanced gene expression of the thermogenesis effector UCP1, the beige-selective gene TMEM26 and the PRDM16, an essential gene for brown-like phenotype maintenance in the beige adipocytes when compared to their counterparts. The enhanced CIDEA and the reduced UCP1 gene levels might justify the white phenotype predominance after the treatment with the PPAR-β/δ agonist.ConclusionsThis work provides evidence that the PPAR-β/δ agonist ameliorated metabolic disorders through enhanced beta-oxidation and better tolerance to glucose, whereas the PPAR-α agonism was confirmed as a promising therapeutic target for treating metabolic diseases via beige cell induction and enhanced thermogenesis.

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New Findings r What is the central question of this study?Telmisartan, an antihypertensive, has beneficial side-effects through its peroxisome proliferator-activated receptor (PPAR) β/δ agonism in white adipose tissue, besides its well-known property of partial PPARγ agonism. Here, we investigated a potential pan-PPAR role of this drug in the white and brown adipose tissues. r What is the main finding and its importance? A. Penna-de-Carvalho and others telmisartan ameliorates inflammation and insulin resistance, as well as inducing non-shivering thermogenesis. Our results point to new therapeutic targets for the control of obesity and comorbidities through pan-PPAR-related effects.

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