Renin–Angiotensin System in Liver Metabolism: Gender Differences and Role of Incretins

Abstract

The impaired hepatic lipids and carbohydrates metabolism result in various metabolic disorders, including obesity, diabetes, insulin resistance, hyperlipidemia and metabolic syndrome. The renin–angiotensin system (RAS) has been identified in the liver and it is now recognized as an important modulator of body metabolic processes. This review is intended to provide an update of the impact of the renin–angiotensin system on lipid and carbohydrate metabolism, regarding gender difference and prenatal undernutrition, specifically focused on the role of the liver. The discovery of angiotensin-converting enzyme 2 (ACE2) has renewed interest in the potential therapeutic role of RAS modulation. RAS is over activated in non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma. Glucagon-like peptide-1 (GLP-1) has been shown to modulate RAS. The GLP-I analogue liraglutide antagonizes hepatocellular steatosis and exhibits liver protection. Liraglutide has a negative effect on the ACE/AngII/AT1R axis and a positive impact on the ACE2/Ang(1-7)/Mas axis. Activation of the ACE2/Ang(1-7)/Mas counter-regulatory axis is able to prevent liver injuries. Angiotensin(1-7) and ACE2 shows more favorable effects on lipid homeostasis in males but there is a need to do more investigation in female models. Prenatal undernutrition exerts long-term effects in the liver of offspring and is associated with a number of metabolic and endocrine alterations. These findings provide a novel therapeutic regimen to prevent and treat many chronic diseases by accelerating the effect of the ACE2/Ang1-7/Mas axis and inhibiting the ACE/AngII/AT1R axis.

تثبيط جملة الرينين-أنجيوتنسين يحسن الصيغة اللبيدية لدى مرضى الداء الكلوي المزمن

“…Angiotensin II, a mediator of RAS, has emerged as a multifunctional cytokine with growth factor, pro-fibrogenic and pro-inflammatory properties. Angiotensin II also plays a role in lipid metabolism [7] . Ma et al [8] reported that angiotensin II induced lipid accumulation in human renal mesangial cells (HMCs).…”

Pea protein hydrolysate reduces blood glucose in high-fat diet and streptozotocin-induced diabetic mice

“…The RAS plays a major role in regulating blood pressure, while emerging evidence suggested that dysregulated RAS might be associated with metabolic disorders, such as hyperglycemia ( 36 ). In particular, the hepatic RAS was implicated to affect the hepatic glucose production ( 37 ). In the RAS, the ACE/AT1 axis exerts detrimental effects, while, the ACE2/MasR axis plays a counter-balancing role ( 38 ).…”

Partial Replacement of NaCl with KCl in Cooked Meat Could Reduce the Liver Damage Through Renin–Angiotensin System in Mice

“…[ 24 ] The ACE/AngII/AT1R axis is described as a cascade in which renin converts angiotensinogen to Ang I, which is converted to Ang II by ACE. [ 25 ] ACE2 catalyzes the conversion of Ang II to Ang 1–7, ACE2/Ang 1–7/Mas axis intrinsically induced protective actions by countering regulation ACE‐Ang II‐AT1R axis. [ 26 ] The local RAS system exists in liver tissue, independent of the circulating RAS, [ 26 ] and the local RAS was identified as an important metabolic system that plays an essential role in lipid homeostasis.…”