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

Abstract

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.

L-Carnitine Is Involved in Hyperbaric Oxygen-Mediated Therapeutic Effects in High Fat Diet-Induced Lipid Metabolism Dysfunction

“…This result is consistent with Leduc-Gaudet et al [55], in which HFD increased CPT1b expression levels in skeletal muscles. Another study reported no statistical difference in CPT1b expression levels following HFD, but fenofibrate, a PPARα agonist significantly decreased its expression [56]. In the current study, HBO treatment both enhanced PPARα expression and decreased CPT1b expression.…”

Protective effect of fenofibrate against high‐fat–high‐fructose diet induced non‐obese NAFLD in rats

“…After accommodation, rats were divided into four equal groups, where the first group was kept as control group (Group I) that were fed on basal diet according to Table 1 . The second group was named as (Group II) and was fed on normal diet for 2 weeks, and then, fenofibrate was given with (50 mg/kg/day) orally [12] for another 4 weeks. The third group (Group III) were fed on normal diet mixed with palm oil 25%, and given 60% fructose solution orally for 4 weeks, and the last group (Group IV) was fed on normal diet mixed with palm oil 25%, and given 60% fructose solution orally, with oral fenofibrate (50 mg/kg/day) for 4 weeks.…”

Effect of Low-Fat Diet in Obese Mice Lacking Toll-like Receptors

“…Inhibition of miR-378a expression attenuated lipolysis and decreased the expression of lipolytic genes, while over-expression of miR-378a increased the expression of lipolytic regulators [ 75 ]. In addition, the expression of miR-103-3p and miR-1a has been reported to regulate the genes related to glucose and fatty acid metabolism [ 76 ] and miR-23a-3p , to be associated with obesity and insulin resistance [ 77 ]. However, no related reports regarding the miR-10a-5p , miR-145a-5p , miR-192a-5p , and miR-34c with obesity or adipogenesis had been reported earlier.…”