Nonalcoholic fatty liver disease shows significant sex dimorphism

Figure 1 Overview of sex differences in etiology and pathogenesis of nonalcoholic fatty liver disease. Men store more visceral adipose tissue than women. Adipokines mediate fat metabolism, and adiponectin can increase lipolysis; however, excessive leptin can lead to insulin resistance and steatosis. The estrogen receptor plays an important role in the regulation of fat metabolism. Increased androgen levels in women and low testosterone in men are prone to visceral fat accumulation. In the process of fatty acid metabolism, men tend to synthesize, and women tend to oxidize. We found that the overexpression of liver pyruvate kinase can lead to changes in liver mitochondrial function, which leads to the deformation of liver fat. The difference in intestinal microflora between men and women also plays a role in the sex difference in nonalcoholic fatty liver disease (NAFLD). In addition, sleep quality, high sugar intake and diet quality can also affect the formation of NAFLD. VLDL: Very low-density lipoprotein; DNL: De novo lipogenesis; TG: Triglyceride; LPK: Liver pyruvate kinase; FA: Fatty acid; NAFLD: Nonalcoholic fatty liver disease.

Figure 2 Sex differences in intrahepatic and extrahepatic outcomes in nonalcoholic fatty liver disease. As a metabolic disorder, nonalcoholic fatty liver disease (NAFLD) is related not only to liver injury but also to a variety of extrahepatic diseases. The picture summarizes the differences between men and women in this respect. Without the protection of estrogen, men have more serious liver fibrosis than women and are more likely to develop liver cancer. The incidence of cardiovascular events and colorectal adenoma in men with NAFLD is higher than that in women. However, female patients have more severe hepatocyte injury and inflammation than male patients and have a higher risk of erosive esophagitis and type 2 diabetes.