短链脂肪酸对肥胖的调控机制研究进展

Research progress on the regulation mechanism of short-chain fatty acids on obesity

肥胖与血脂异常、胰岛素抵抗、代谢性炎性反应、动脉粥样硬化和非酒精性脂肪肝等疾病密切相关。肠道菌群代谢膳食纤维产生的短链脂肪酸(short-chain fatty acids,SCFAs)可以降低肥胖等慢性代谢性疾病的患病风险,在机体肠道营养、能量平衡、肠道菌群稳态、生理功能调节中起着重要作用。SCFAs可通过以下机制影响食欲和能量摄入:通过激活过氧化物酶体增殖物激活受体γ(peroxisome proliferatoractivated receptorγ,PPARγ)的表达,预防和逆转高脂饮食诱导的肝脏脂质代谢异常;通过干预肠脑轴的营养感应和信号传递,调节食欲以控制能量平衡;为肠道菌群提供能量,同时作为信号分子被细胞表面G蛋白偶联受体(G protein-coupled receptors,GPCRs)识别,激活下游信号通路,调控脂质代谢;介导饮食和运动对肠道激素分泌、脂质和能量代谢的调节。SCFAs作为营养靶点具有预防和改善肥胖的潜力,全面深入理解SCFAs在新陈代谢中的作用可为保持机体能量稳态,改善肥胖及相关慢性代谢性疾病提供有益参考。

Excessive food intake,especially a high-fat,high-sugar diet,and insufficient exercise are considered major risk factors for obesity.Obesity is closely associated with diseases such as dyslipidemia,insulin resistance,metabolic inflammation,atherosclerosis,and non-alcoholic fatty liver disease.Therefore,it is of great theoretical and practical significance to explore new strategies to prevent and improve obesity.Epidemiological and experimental studies have shown that short-chain fatty acids(SCFAs)produced by gut microbiota metabolizing dietary fiber can reduce the risk of chronic metabolic diseases such as obesity.As important regulators of energy metabolism,SCFAs play an important role in intestinal nutrition,energy balance,gut microbiota homeostasis,and physiological function.SCFAs can affect appetite and energy intake through the following mechanisms:SCFAs can prevent and reverse high-fat diet-induced abnormal hepatic lipid metabolism by activating the expression of peroxisome proliferator-activated receptor gamma(PPARy);SCFAs can regulate appetite by intervening in the nutrient-sensing and signal transduction of the gut-brain axis to control energy balance;SCFAs can provide energy for the gut microbiota and are recognized as signaling molecules by G protein-coupled receptors(GPCRs)on the cell surface,activating downstream signaling pathways to regulate lipid metabolism;SCFAs can mediate the regulation of dietary and exercise on gut hormone secretion,lipid and energy metabolism.As nutritional targets,SCFAs have the potential to prevent and improve obesity.A comprehensive and in-depth understanding of the role of SCFAs in metabolism will provide a beneficial reference for maintaining the body's energy homeostasis and improving obesity and related chronic metabolic diseases.