Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes

Autor(es):Mostrar menos -

Frias, Flavia de T. ^[1] ; Rocha, Karina C. E. ^[1] ; de Mendonca, Mariana ^[1] ; Murata, Gilson M. ^[2] ; Araujo, Hygor N. ^{[3, 4]} ; de Sousa, Luis G. O. ^[1] ; de Sousa, Erica ^[1] ; Hirabara, Sandro M. ^[5] ; Leite, Nayara de C. ^{[3, 4]} ; Carneiro, Everardo M. ^{[3, 4]} ; Curi, Rui ^{[2, 5]} ; Silveira, Leonardo R. ^{[3, 4]} ; Rodrigues, Alice C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil

^[3] Obes & Comorbid Res Ctr, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Dept Struct & Funct Biol, Inst Biol, Sao Paulo - Brazil

^[5] Cruzeiro do Sul Univ, Interdisciplinary Postgrad Program Hlth Sci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 233, n. 4, p. 3515-3528, APR 2018.
• Citações Web of Science: 4

Resumo

The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet-induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high-fat diet for 8 weeks. Fenofibrate (50mg/Kg BW, daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin-stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR-103-3p in adipose tissue, and miR-1a, miR-133a/b, miR-206, let7b-5p, miR-23b-3p, miR-29-3p, miR-143-3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho-AMPK2, Pgc1, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated. In DIO mice, fenofibrate prevented weight gain induced by HFD feeding by increasing energy expenditure; improved whole body glucose homeostasis, and in skeletal muscle, increased insulin dependent glucose uptake, miR-1a levels, reduced intramuscular lipid accumulation, and phospho-AMPK2 levels. In visceral adipose tissue of obese mice, fenofibrate decreased basal lipolysis rate and visceral adipocytes hypertrophy, and induced the expression of Glut-4, Irs1, and Cav-1 mRNA and miR-103-3p suggesting a higher insulin sensitivity of the adipocytes. The evidence is presented herein that beneficial effects of fenofibrate on body weight, glucose homeostasis, and muscle metabolism might be related to its action in adipose tissue. Moreover, fenofibrate regulates miR-1a-3p in soleus and miR-103-3p in adipose tissue, suggesting these microRNAs might contribute to fenofibrate beneficial effects on metabolism. (AU)

• Processo FAPESP: 11/05876-6 - Avaliação de microRNAs no desenvolvimento da resistência à insulina
• Beneficiário: Alice Cristina Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/24789-8 - MicroRNAs na via de sinalização de adiponectina: possíveis alvos terapêuticos na melhora da resistência à insulina e de doenças associadas.
• Beneficiário: Alice Cristina Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular