High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue

Abstract

Dietary L-arginine (Arg) supplementation reduces white-fat gain in diet-induced obese rats but the underlying mechanisms are unknown. This study tested the hypothesis that Arg treatment affects expression of genes related to lipid metabolism in adipose tissue. Four-week-old male Sprague-Dawley rats were fed a low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, lean or obese rats continued to be fed their same respective diets and received drinking water containing 1.51% Arg-HCl or 2.55% L: -alanine (isonitrogenous control). After 12 weeks of Arg supplementation, rats were euthanized to obtain retroperitoneal adipose tissue for analyzing global changes in gene expression by microarray. The results were confirmed by RT-PCR analysis. HF feeding decreased mRNA levels for lipogenic enzymes, AMP-activated protein kinase, glucose transporters, heme oxygenase 3, glutathione synthetase, superoxide dismutase 3, peroxiredoxin 5, glutathione peroxidase 3, and stress-induced protein, while increasing expression of carboxypeptidase-A, peroxisome proliferator activated receptor (PPAR)-alpha, caspase 2, caveolin 3, and diacylglycerol kinase. In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPARgamma, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein. Biochemical analysis revealed oxidative stress in white adipose tissue of HF-fed rats, which was prevented by Arg supplementation. Collectively, these results indicate that HF diet and Arg supplementation differentially regulate gene expression to affect energy-substrate oxidation, redox state, fat accretion, and adipocyte differentiation in adipose tissue. Our findings provide a molecular mechanism to explain a beneficial effect of Arg on ameliorating diet-induced obesity in mammals.

Effects of starter diet supplementation with arginine on broiler production performance and on small intestine morphometry

“…There is evidence for the participation of adjustment mechanisms between intrinsic and primary extrinsic afferent neurons and the central nervous system in addition to enzyme gene transcription mechanisms, and even gene expression, as speciϐi-cally reported for some amino acids, such as Arg & Gln (Fu et al 2005, Wang et al 2008, Jobgen et al 2009, Wu 2009.…”

“…They also regulate gene expression in highly speciϐic processes that involve the transfer of coded information from a gene to its product (RNA and/or protein). In mammals, research has shown that dietary supplementation with Arg and glycine (Gln) can increase the expression of antioxidant genes and reduce the expression of proinϐlammatory genes in the small intestine and adipose tissue (Fu et al 2005, Wang et al 2008, Jobgen et al 2009). …”

Inhibition of adipogenic differentiation by myostatin is alleviated by arginine supplementation in porcine-muscle-derived mesenchymal stem cells

“…Arginine is a conditionally essential amino acid for pregnant and lactating sows and newborn piglets, and is important for the growth and development of the fetus and neonate [9][10][11]. A high-fat diet and arginine supplementation were recently reported by Jobgen et al to differentially regulate gene expression and affect energy-substrate oxidation, redox state, fat accretion, and adipocyte differentiation in adipose tissue, and a beneficial effect of arginine on ameliorating diet-induced obesity in rats was demonstrated [33]. Dietary supplementation with arginine increased muscle gain and decreased subcutaneous fat deposition in growing-finishing pigs, and, arginine enhanced longissimus dorsi muscle protein, glycogen, and fat contents by 4.8%, 42%, and 70%, respectively [12].…”

Functional amino acids in nutrition and health

“…Moreover, leucine activates the mammalian target of rapamycin to stimulate protein synthesis and inhibit intracellular proteolysis (Dillon 2012;Li et al 2011b), whereas methionine is the major donor of the methyl group to affect DNA and protein methylation in cells (Wang et al 2012). Notably, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression and enhances growth of the small intestine and skeletal muscle (Geng et al 2011;Jobgen et al 2009;Wang et al 2008;Wu et al 2011a, b; Regulation of acid-base balance (e.g., renal ammoniagenesis from glutamine)…”