Mastoor Zainab, Diz-Chaves Yolanda, González-Matías Lucas C, Mallo Federico
Biomedical Research Centre (CINBIO), University of Vigo, 36310 Vigo, Spain.
Metabolites. 2022 May 3;12(5):411. doi: 10.3390/metabo12050411.
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.
肝脏脂质和碳水化合物代谢受损会导致各种代谢紊乱，包括肥胖、糖尿病、胰岛素抵抗、高脂血症和代谢综合征。肝脏中已发现肾素-血管紧张素系统（RAS），现在它被认为是身体代谢过程的重要调节因子。本综述旨在提供肾素-血管紧张素系统对脂质和碳水化合物代谢影响的最新情况，涉及性别差异和产前营养不足，特别关注肝脏的作用。血管紧张素转换酶2（ACE2）的发现重新激发了人们对RAS调节潜在治疗作用的兴趣。RAS在非酒精性脂肪性肝病（NAFLD）和肝细胞癌中过度激活。胰高血糖素样肽-1（GLP-1）已被证明可调节RAS。GLP-1类似物利拉鲁肽可拮抗肝细胞脂肪变性并具有肝脏保护作用。利拉鲁肽对ACE/AngII/AT1R轴有负面影响，对ACE2/Ang(1-7)/Mas轴有积极影响。激活ACE2/Ang(1-7)/Mas反调节轴能够预防肝损伤。血管紧张素(1-7)和ACE2对男性脂质稳态显示出更有利的影响，但需要在雌性模型中进行更多研究。产前营养不足会对后代肝脏产生长期影响，并与许多代谢和内分泌改变有关。这些发现为通过加速ACE2/Ang1-7/Mas轴的作用和抑制ACE/AngII/AT1R轴来预防和治疗许多慢性疾病提供了一种新的治疗方案。
