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

Autor: Frias FT; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Rocha KCE; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., de Mendonça M; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Murata GM; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Araujo HN; Obesity and Comorbidities Research Center, Campinas, Sao Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil., de Sousa LGO; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., de Sousa É; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Hirabara SM; Interdisciplinary Post-Graduate Program in Health Science, Cruzeiro do Sul University, Sao Paulo, Brazil., Leite NC; Obesity and Comorbidities Research Center, Campinas, Sao Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil., Carneiro EM; Obesity and Comorbidities Research Center, Campinas, Sao Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil., Curi R; Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.; Interdisciplinary Post-Graduate Program in Health Science, Cruzeiro do Sul University, Sao Paulo, Brazil., Silveira LR; Obesity and Comorbidities Research Center, Campinas, Sao Paulo, Brazil.; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil., Rodrigues AC; Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2018 Apr; Vol. 233 (4), pp. 3515-3528. Date of Electronic Publication: 2017 Nov 01.
DOI: 10.1002/jcp.26203
Abstrakt: 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 (50 mg/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-AMPKα2, Pgc1α, 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-AMPKα2 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.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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