Dietary L-arginine supplementation increases the hepatic expression of AMP-activated protein kinase in rats.

Abstract

The goal of this study was to elucidate the molecular mechanisms responsible for the anti-obesity effect of L-arginine supplementation in diet-induced obese rats. Male Sprague-Dawley rats were fed either a low-fat or high-fat diet for 15weeks. Thereafter, lean or obese rats were pair-fed their same respective diets and received drinking water containing either 1.51% L-arginine-HCl or 2.55% L-alanine (isonitrogenous control) for 12weeks. Gene and protein expression of key enzymes in the metabolism of energy substrates were determined using real-time polymerase-chain reaction and western blotting techniques. The mRNA levels of hepatic fatty acid synthase and stearoyl-CoA desaturase were reduced (P < 0.05) but those of hepatic AMP-activated protein kinase-α (AMPKα), peroxisome proliferator activator receptor γ coactivator-1α, and carnitine palmitoyltransferase I (CPT-I), as well as skeletal muscle CPT-I were increased (P < 0.05) by L-arginine treatment. The protein expression and activity of hepatic AMPKα markedly increased (P < 0.05) but the activity of hepatic acetyl-CoA carboxylase (ACC) decreased (P < 0.05) in response to dietary L-arginine supplementation. Collectively, our results indicate that liver is the major target for the action of dietary L-arginine supplementation on reducing white-fat mass in diet-induced obese rats by inhibiting fatty acid synthesis and increasing fatty acid oxidation via the AMPK-ACC signaling pathway. Additionally, increased CPT-I expression in skeletal muscle may also contribute to the enhanced oxidation of long-chain fatty acids in L-arginine-supplemented rats.