Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice

Abstract

Abstract. Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucinearginine-proline (LRP) and leucine-glutamine-proline (LQP)] from wheat bran autolytic hydrolysate. The present study aimed to investigate the effects of LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also evaluated the effects of these peptides on oxidative stress and on the AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic factors of NASH. Seven-week-old male C57BL/6 mice were fed a high-fat diet for 10 weeks and administered water supplemented with 0.05% LRP, 0.20% LRP, 0.05% LQP, or 0.20% LQP (each n=5) or distilled water (control; n=5) ad libitum. Oxidative stress was evaluated by measuring the serum levels of diacron reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) were evaluated by immunoblotting. The result showed that non-alcoholic fatty liver disease activity score was significantly decreased in all types of treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that the expression of phospho-AMPK was increased whereas that of phospho-ACC was decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse model. In addition, we showed that LRP and LQP modulated oxidative stress and upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically applicable therapeutic agents for NASH. IntroductionNon-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The prevalence of NAFLD is estimated to range from 25 to 37% of the general population (1-4), and it constitutes a common etiological factor of chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH) is a progressive form of NAFLD. Patients with NASH have a high risk of life-threatening complications, including cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma (5,6). In addition, NASH is predicted to become the leading cause of liver transplantation in the USA by the year 2020 (2). Thus, NAFLD/NASH is becoming a major social issue worldwide.The first-line therapy for NASH is life-style intervention. Although diet and exercise alleviate the severity of NASH, long-term adherence to life-style interventions is poor (7,8). Pioglitazone, an insulin-sensitizing anti-diabetic agent, leads to metabolic and histologic improvement in patients with NASH (9). However, the indication of pioglitazone is restricted to NASH patients with diabetes mellitus (10). Furthermore, severe liver disease is a contrai...

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.…”

Antidiabetic properties of rice and wheat bran—A review

“…showed that liver function and glucose metabolisms were ameliorated. However, no biochemical experimentation was performed for liver function and glucose metabolisms such as glucose tolerance test and insulin tolerance test (Kawaguchi et al, 2017). muscle cells (20.4%) that indicates RBE can be a potent candidate in diabetic management (Arun et al, 2020).…”

Propiedades y posibles aplicaciones de las proteínas de salvado de trigo

“…nas de las capas externa e intermedia son bá-sicamente enzimas que actúan contra el estrés oxidativo y contra patógenos que sobreviven a la deshidratación, enzimas hidrolíticas necesarias para la germinación, así como inhibidores de otras enzimas (Jerkovic y col., 2010;Koehler y Wieser, 2013). Las proteínas de la capa aleurona están constituidas en un 58 % por globulinas, aproximadamente, cuya función principal es la de reserva para su uso durante la germinación; el restante 42 % tiene actividad enzimática (Jerkovic y col., 2010; Meziani y col., 2012).…”