title: PPAR-α agonist elicits metabolically active brown adipocytes and weight loss in diet-induced obese mice.
abstract: Obesity is considered a public health problem worldwide. Fenofibrate, a selective peroxisome proliferator-activated receptor α (PPAR-α) agonist, elicits weight loss in animal models. This study aimed to examine the effects of fenofibrate on energy expenditure, body mass (BM) and gene expression of thermogenic factors in brown adipose tissue of diet-induced obese mice. Male C57BL/6 mice were fed a standard chow (SC; 10% lipids) diet or a high-fat (HF; 50% lipids) diet for 10 weeks. Afterwards, groups were subdivided as SC, SC-F, HF and HF-F (n = 10, each). Treatment with fenofibrate (100 mg kg(-1) BM mixed into the diet) lasted 5 weeks. Treated groups had reduced final BM compared with their counterparts (p < 0·05), explained by the increase in energy expenditure, CO2 production and O2 consumption after treatment with fenofibrate (p < 0·05). Similarly, genes involved in thermogenesis as PPAR-α, PPAR-γ coactivator 1α, nuclear respiratory factor 1, mitochondrial transcription factor A (Tfam), PR domain containing 16 (PRDM16), β-3 adrenergic receptor (β3-AR), bone morphogenetic protein 8B and uncoupling protein 1 were significantly expressed in brown adipocytes after the treatment (p < 0·05). All observations ensure that selective PPAR-α agonist can induce thermogenesis by increasing energy expenditure and enhancing the expression of genes involved in the thermogenic pathway. These results suggest fenofibrate as a coadjutant drug for the treatment of obesity.
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Tamiris Lima
authors.initials: TL
authors.lastname: Rachid
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Penna-de-Carvalho
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Isabele
authors.initials: I
authors.lastname: Bringhenti
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marcia Barbosa
authors.initials: MB
authors.lastname: Aguila
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Mandarim-de-Lacerda
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D012333:RNA, Messenger; D011345:Fenofibrate
keywords: NRF-1; PPAR-α; UCP-1; brown adipocytes; obesity; thermogenesis