Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats

Abstract

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.

Branched chain amino acids alter fatty acid profile in colostrum of sows fed a high fat diet

“…BCAAs were reported to reduce hyperlipidemia, hepatic lipid accumulation [8,31,32], and obesity (reviewed by [33]) but the intrinsic mechanism was not clear yet. Indirect evidences include in vivo studies that revealed BCAAs upregulate the lipid catabolic genes carnitine palmitoyltransferase I and PPARα [34] and downregulate the hepatic lipogenic genes acetyl-CoA carboxylase α and stearoyl-coAdesaturase 1 in chicks [35].…”

“…The catabolic intermediate of valine, 3-hydroxy-isobutyrate, is a paracrine regulator of fatty acid flux [7]. Feeding high fat diets with the inclusion of BCAA to rodents reduces obesity and hepatocyte fat deposition [8]. In finishing pigs, isoleucine supplementation increase lipogenesis in intramuscular fat [9].…”

Branched chain amino acids are associated with the heterogeneity of the area of lipid droplets in hepatocytes of patients with non‐alcoholic fatty liver disease

“…Furthermore, the supplementation of BCAAs did not improve the liver dysfunction of ob/ob mice. Previous studies reported the beneficial effects of BCAA on hepatic steatosis in NAFLD/NASH mouse models . The discrepancy might be led by differences in model mice or rats.…”

“…Previous studies reported the beneficial effects of BCAA on hepatic steatosis in NAFLD/NASH mouse models. [34][35][36] The discrepancy might be led by differences in model mice or rats. Leptin-deficient ob/ob mice induced more severe steatosis and liver dysfunction than the diet-induced model.…”

Dietary protein and blood glucose control

“…When animals were fed a high-fat diet to induce an insulin resistance, an increase of protein or amino acid intake has been reported to improve liver steatosis with decreased de novo lipogenesis fluxes, reduced expression of lipogenic genes, lower postprandial insulin secretion, and improved glucose tolerance; this was associated with restored expression of muscle insulin signaling proteins repressed by a high-fat diet [40]. Four-week or 8-week supplementation with leucine reduced fat deposition in liver [41,42] by enhancing VLDL lipid secretion. Chronic leucine supplementation increases insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in liver, skeletal muscle, and adipose tissue of rats fed high fat diet [43].…”