Sex-specific effects of PNPLA3 I148M

被引:3
作者
Cherubini, Alessandro [1 ]
Rosso, Chiara [2 ]
Della Torre, Sara [3 ]
机构
[1] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Precis Med Biol Resource Ctr, Dept Transfus Med, Precis Med, Via Francesco Sforza 35, I-20122 Milan, Italy
[2] Univ Turin, Dept Med Sci, Turin, Italy
[3] Univ Milan, Dept Pharmaceut Sci, Milan, Italy
关键词
hepatocellular carcinoma (HCC); human liver organoids; metabolic dysfunction-associated steatotic liver disease (MASLD); sexual dimorphism; LIPID DROPLETS; LIVER FIBROSIS; DISEASE; SUSCEPTIBILITY; SEVERITY; VARIANT;
D O I
10.1111/liv.16088
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Metabolic dysfunction-associated steatotic liver disease (MASLD, previously termed NAFLD, nonalcoholic fatty liver disease) is a complex multifactorial disease showing generally higher prevalence and severity in men than in women. With respect to women, men are also more prone to develop metabolic dysfunction-associated steatohepatitis, fibrosis and liver-related complications. Several genetic, hormonal, environmental and lifestyle factors may contribute to sex differences in MASLD development, progression and outcomes. However, after menopause, the sex-specific prevalence of MASLD shows an opposite trend between men and women, pointing to the relevance of oestrogen signalling in the sexual dimorphism of MASLD. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, that encodes a triacylglycerol lipase that plays a crucial role in lipid metabolism, has emerged as a key player in the pathogenesis of MASLD, with the I148M variant being strongly associated with increased liver fat content and disease severity. Recent advances indicate that carrying the PNPLA3 I148M variant can be a risk factor for MASLD especially for women. To elucidate the molecular mechanisms underlying the sex-specific role of PNPLA3 I148M in the development of MASLD, several in vitro, ex vivo and in vivo models have been developed.
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页数:8
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