Abstract:
Metabolic-associated steatotic liver disease (MASLD) is closely associated with obesity. MASLD affects over 1 billion adults globally but there are few treatment options available. Glucagon is a key metabolic regulator, and its actions include the reduction of liver fat through direct and indirect means. Chronic glucagon signalling deficiency is associated with hyperaminoacidaemia, hyperglucagonaemia and increased circulating levels of glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF-21). Reduction in glucagon activity decreases hepatic amino acid and triglyceride catabolism; metabolic effects include improved glucose tolerance, increased plasma cholesterol and increased liver fat. Conversely, glucagon infusion in healthy volunteers leads to increased hepatic glucose output, decreased levels of plasma amino acids and increased urea production, decreased plasma cholesterol and increased energy expenditure. Patients with MASLD share many hormonal and metabolic characteristics with models of glucagon signalling deficiency, suggesting that they could be resistant to glucagon. Although there are few studies of the effects of glucagon infusion in patients with obesity and/or MASLD, there is some evidence that the expected effect of glucagon on amino acid catabolism may be attenuated. Taken together, this evidence supports the notion that glucagon resistance exists in patients with MASLD and may contribute to the pathogenesis of MASLD. Further studies are warranted to investigate the direct effects of glucagon on metabolism in patients with MASLD.
摘要:
代谢相关脂肪变性肝病(MASLD)与肥胖密切相关。MASLD影响全球超过10亿成年人,但几乎没有可用的治疗选择。胰高血糖素是一种关键的代谢调节因子,其作用包括通过直接和间接手段减少肝脏脂肪。慢性胰高血糖素信号缺乏与高氨基酸血症有关,高胰高血糖素血症,胰高血糖素样肽1(GLP-1)和成纤维细胞生长因子21(FGF-21)的循环水平增加。胰高血糖素活性的降低会降低肝脏氨基酸和甘油三酯的分解代谢;代谢作用包括改善葡萄糖耐量,增加血浆胆固醇和增加肝脏脂肪。相反,在健康志愿者中输注胰高血糖素导致肝脏葡萄糖输出增加,血浆氨基酸水平降低,尿素产量增加,降低血浆胆固醇和增加能量消耗。MASLD患者与胰高血糖素信号缺乏模型共享许多激素和代谢特征,表明它们可能对胰高血糖素有抗药性.尽管很少有关于胰高血糖素输注对肥胖和/或MASLD患者的影响的研究,有证据表明胰高血糖素对氨基酸分解代谢的预期作用可能减弱。一起来看,该证据支持MASLD患者存在胰高血糖素抵抗的观点,并且可能与MASLD的发病机制有关.有必要进一步研究胰高血糖素对MASLD患者代谢的直接影响。