The metabolic triad of non-alcoholic fatty liver disease, visceral adiposity and type 2 diabetes: Implications for treatment

被引:30
作者
Cariou, Bertrand [1 ]
机构
[1] Univ Nantes, Inst Thorax, CHU Nantes, Inserm,CNRS, F-44000 Nantes, France
关键词
adipocyte; bariatric surgery; GLP-1; insulin resistance; NASH; PPAR; LIFE-STYLE MODIFICATION; INSULIN-RESISTANCE; WEIGHT-LOSS; HEPATIC STEATOSIS; MITOCHONDRIAL-FUNCTION; BARIATRIC SURGERY; DOUBLE-BLIND; STEATOHEPATITIS; TISSUE; OBESE;
D O I
10.1111/dom.14651
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Non-alcoholic fatty liver disease (NAFLD) is associated with visceral obesity, insulin resistance, type 2 diabetes (T2D) and has been often considered as the hepatic expression of the metabolic syndrome (MetS). Epidemiological studies highlight a bidirectional relationship of NAFLD with T2D in which NAFLD increases the risk of incident T2D and T2D increases the risk of severe non-alcoholic steatohepatitis (NASH) and liver fibrosis. Regarding the molecular determinants of NAFLD, we specifically focused in this review on adipocyte dysfunction as a key molecular link between visceral adipose tissue, MetS and NAFLD. Notably, the subcutaneous white adipose tissue expandability appears a critical adaptive buffering mechanism to prevent lipotoxicity and its related metabolic complications, such as NAFLD and T2D. There is a clinical challenge to consider therapeutic strategies targeting the metabolic dysfunction common to NASH and T2D pathogenesis. Strategies that promote significant and sustained weight loss (similar to 10% of total body weight) such as metabolic and bariatric surgery or incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP or GLP-1/glucagon receptor co-agonists) are among the most efficient ones. In addition, insulin sensitizers such as PPAR gamma (pioglitazone) and pan-PPARs agonists (lanifibranor) have shown some beneficial effects on both NASH and liver fibrosis. Since NASH is a complex and multifactorial disease, it is conceivable that targeting different pathways, not only insulin resistance but also inflammation and fibrotic processes, is required to achieve NASH resolution.
引用
收藏
页码:15 / 27
页数:13
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