Fenofibrate improves insulin sensitivity in connection with intramuscular lipid content, muscle fatty acid-binding protein, and beta-oxidation in skeletal muscle

Abstract

We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acidbinding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a -oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of -oxidation in muscles.

Effect and the related signaling pathways of insulin influencing lipid metabolism in yellow catfishPelteobagrus fulvidraco

“…Zheng et al (2015a) found that PPARα was highly expressed in the liver in yellow catfish, and fenofibrate exerted lipid-lowering activity via activation of PPARα, leading to altered expression of genes involved in lipid metabolism. Fenofibrate addition also down-regulated the mRNA levels of G6PD and 6PGD, and reduced the insulin-induced TG accumulation, in agreement with other reports (Idzior-Walus et al, 2000;Furuhashi et al, 2002). Here, GW6471 pre-treatment significantly reduced the insulin-induced up-regulation of expression of FAS, G6PD and 6PGD, further indicating that the PPARα signaling pathway is involved in the insulin-induced change of lipid metabolism in yellow catfish.…”

Blockade of the Renin-Angiotensin System Increases Adiponectin Concentrations in Patients With Essential Hypertension

“…This raises the idea that the effect of RAS blockade on adiponectin levels is, at least partly, mediated by the decrease in insulin levels, which is secondary to the effect of RAS blockade on enhancing insulin sensitivity. Although administration of thiazolidinediones, peroxisome proliferator-activated receptor (PPAR)␥ agonists, has been shown to increase adiponectin concentrations, [11][12][13] treatment with metformin, a non-PPAR␥-associated antihyperglycemic agent, or fenofibrate, a PPAR␣ agonist that has recently been shown to improve insulin sensitivity, 29 has been reported to have no effect on adiponectin concentrations in mice. 13 This indicates that the change in adiponectin concentrations is not simply a consequence of an improved metabolic phenotype and that the change in adiponectin levels is indeed (directly or indirectly) RAS blockade-mediated.…”

Towards Fish Lipid Nutrigenomics: Current State and Prospects for Fin-Fish Aquaculture

“…For example, heart FABP is considered to shuttle fatty acids from the plasma membrane to mitochondria for β-oxidation while the adipocyte FABP is considered to facilitate efflux of lipolytically-derived fatty acids (Londraville and Sidell, 1996;Coe and Bernlohr, 1998). In rat heart and muscle there is a clear correlation between fatty acid oxidation and cytosolic FABP content (Veerkamp and Vanmoerkerk, 1993;Furuhashi et al 2002).…”