title: Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice.
abstract: Browning is characterized by the formation of beige/brite fat depots in subcutaneous white adipose tissue (sWAT). This study aimed to examine whether the chronic activation of PPARalpha by fenofibrate could induce beige cell depots in the sWAT of diet-induced obese mice. High-fat fed animals presented overweight, insulin resistance and displayed adverse sWAT remodeling. Fenofibrate significantly attenuated these parameters. Treated groups demonstrated active UCP-1 beige cell clusters within sWAT, confirmed through higher gene expression of PPARalpha, PPARbeta, PGC1alpha, BMP8B, UCP-1, PRDM16 and irisin in treated groups. PPARalpha activation seems to be pivotal to trigger browning through irisin induction and UCP-1 transcription, indicating that fenofibrate increased the expression of genes typical of brown adipose tissue (BAT) in the sWAT, characterizing the formation of beige cells. These findings put forward a possible role of PPARalpha as a promising therapeutic for metabolic diseases via beige cell induction.
authors.affiliation: Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of 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, 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, 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, Brazil.
authors.forename: Marcia B
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, Brazil.
authors.forename: Carlos A
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, Brazil. Electronic address: souzamello.uerj@gmail.com.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Souza-Mello
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050260:Carbohydrate Metabolism / Q000187:drug effects; D048429:Cell Size; D054338:Cell Transdifferentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000473:pathology; D000071256:Uncoupling Protein 1
chemical_list: D019440:Anti-Obesity Agents; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D047493:PPAR alpha; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D011345:Fenofibrate
keywords: Beige cells; Browning; Fenofibrate; Irisin; PPARalpha; White adipose tissue