Differential actions of PPAR-[alpha] and PPAR-[beta]/[delta] on beige adipocyte formation: A study in the subcutaneous white adipose tissue of obese male mice

Obesity 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-[alpha] or PPAR-[beta]/[delta] could induce beige cell depots in the subcutaneous white adipose...

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Bibliographic Details
Published in:PloS one 2018-01, Vol.13 (1), p.e0191365
Main Authors: Rachid, Tamiris Lima, Silva-Veiga, Flavia Maria, Graus-Nunes, Francielle, Bringhenti, Isabele, Mandarim-de-Lacerda, Carlos Alberto, Souza-Mello, Vanessa
Format: Article
Language:English
Subjects:
Adipose tissue
Health aspects
Hypertrophy
Metabolic diseases
Obesity
Physiological aspects
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Summary:Obesity 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-[alpha] or PPAR-[beta]/[delta] could induce beige cell depots in the subcutaneous white adipose tissue of diet-induced obese mice. Sixty 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-[alpha] (C plus PPAR-[alpha] agonist, 2.5 mg/kg BM), C-[beta] (C plus PPAR-[beta]/[delta] agonist, 1 mg/kg BM), HF, HF-[alpha] (HF plus PPAR-[alpha] agonist), HF-[beta] (HF plus PPAR-[beta]/[delta] agonist). HF 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-[alpha] treated groups. PPAR-[alpha] 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-[beta]/[delta] agonist. This work provides evidence that the PPAR-[beta]/[delta] agonist ameliorated metabolic disorders through enhanced beta-oxidation and better tolerance to glucose, whereas the PPAR-[alpha] agonism was confirmed as a promising therapeutic target for treating metabolic diseases via beige cell induction and enhanced thermogenesis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0191365