Details

Autor(en) / Beteiligte

• Frias, Flávia de T.
• Rocha, Karina C.e.
• de Mendonça, Mariana
• Murata, Gilson M.
• Araujo, Hygor N.
• de Sousa, Luís G.O.
• de Sousa, Érica
• Hirabara, Sandro M.
• Leite, Nayara de C.
• Carneiro, Everardo M.
• Curi, Rui
• Silveira, Leonardo R.
• Rodrigues, Alice C.

Titel

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

Ist Teil von

• Journal of cellular physiology, 2018-04, Vol.233 (4), p.3515-3528

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. We demonstrated that miR‐1a regulates glucose uptake. Fenofibrate actions in metabolism may be related to its effects on specific miRNA in isolated tissues. Moreover, no other work has evaluated in depth the effect of fenofibrate on muscle and adipose tissue, and more importantly, has shown the crosstalk between these tissues under fenofibrate treatment.