Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity

Abstract

Adropin, a secretory signal peptide, has shown beneficial effects on improving glucose homeostasis and dyslipidemia. However, whether this peptide affects nonalcoholic steatohepatitis (NASH) has remained unclear. In this study, the serum adropin levels, liver injury and oxidative stress were measured in diet-induced NASH mice. Adropin knock-out mice and palmitate treated primary hepatic cells were used to investigate the influence of adropin on liver injury. Our results show that serum adropin levels were decreased and negatively correlated with liver injury in NASH mice. Knockout of adropin significantly exacerbated hepatic steatosis, inflammatory responses and fibrosis in mice after either methionine-choline deficient diet (MCD) or western diet (WD) feeding. And the treatment with adropin bioactive peptides ameliorated NASH progression in mice. Adropin alleviated hepatocyte injury by upregulating the expression of Gclc, Gclm, and Gpx1 in a manner dependent on Nrf2 transcriptional activity and by increasing the glutathione (GSH) levels. And adropin significantly increased CBP expression and promoted its binding with Nrf2, which enhanced Nrf2 transcriptional activity. Furthermore, AAV8-mediated overexpression of hepatic Nrf2 expression functionally restored the liver injury induced by adropin-deficiency MCD-fed mice. These findings provide evidence that adropin activates Nrf2 signaling and plays a protective role in liver injury of NASH and therefore might represent a novel target for the prevention and treatment of NASH.

Adropin as A Fat-Burning Hormone with Multiple Functions—Review of a Decade of Research

“…Furthermore, mice with adropin deficiency have enhanced hepatic steatosis, fibrosis, as well as inflammation (non-alcoholic steatohepatitis-NASH) when fed methionine-choline deficient or western diets. In contrast, synthetic adropin attenuates NASH development in mice [67]. Notably, protective effects of adropin on hepatocytes injury were also confirmed in in vitro cultured hepatocytes.…”

“…Notably, protective effects of adropin on hepatocytes injury were also confirmed in in vitro cultured hepatocytes. Investigation of molecular signaling conferring beneficial effects of adropin peptide against liver damage showed that adropin promotes Nfr2 transcription activity [67]. Downregulation of serum adropin levels was also reported in patients with non-alcoholic liver fatty disease [68].…”

“…Furthermore, upregulation of adropin in serum was positively associated with the severity of alcoholic liver cirrhosis, based on the Child-Pugh score [66]. Chen et al demonstrated that non-alcoholic induction of steatohepatitis causes a fall of adropin levels in serum [67]. Furthermore, mice with adropin deficiency have enhanced hepatic steatosis, fibrosis, as well as inflammation (non-alcoholic steatohepatitis-NASH) when fed methionine-choline deficient or western diets.…”

A comparison of the biological activities of ethyl acetate fractions from the stems and leaves of Penthorum chinense Pursh

“…Whereas DPPH comprises stable free radical molecules, hydrogen peroxide (H 2 O 2 ) is one of ROS which is generated as a short-lived product in biochemical processes, such as β-oxidation of long chain fatty acids [29] . And ROS appears to be a feature of liver diseases [30,31] . Therefore, leaves, not stems, of PCP are an ideal material for use as a liver diseases treatment.…”

A Review of Adropin as the Medium of Dialogue between Energy Regulation and Immune Regulation

“…Adropin activates Nrf2 signaling in nonalcoholic steatohepatitis (NASH) and plays a role in decreasing reactive oxygen species (ROS) production from liver mitochondria. So, it may protect mitochondrial function to alleviate oxidative stress and apoptosis and thus protect against liver injury and prevent the NASH progression [44]. Figure 2: Regulatory mechanisms of adropin for immune cells.…”