Increasing evidence indicates that hepatic fat accumulation is related to hepatic fibrosis, inflammation, apoptosis, and cancer. Males generally have larger visceral fat areas than females. Menopause is associated with a shift towards relatively more fat as well as towards the deposition of more fat in the abdominal region. Estrogen treatment of male-to-female transsexuals can increase the amount of subcutaneous adipose tissue; thus, estrogen changes the male type of visceral fat distribution into a female type of fat accumulation. Visceral fat accumulation arises through enlarged adipocytes, which release adiponectin, leptin, tumor necrosis factor-α (TNF-α), and fatty acids. Adiponectin inhibits the enlargement of adipocytes and fat accumulation. Adiponectin levels are consistently higher in females than in males. Persistent TNF-α stimuli lead to adipogenesis and impairment of mitochondria in hepatocytes and result in induction of oxidative stress. In experimental studies, when incubated with adiponectin, hepatic stellate cells undergo a number of antifibrogenic changes. Whereas leptin may play a role in the development of hepatic fibrosis. Hepatic steatosis spontaneously becomes evident in an aromatase-deficient mouse. Estrogen replacement reduces hepatic steatosis and restores the impairment in mitochondrial fatty acid β-oxidation to a wild-type level. In fact, tamoxifen, as an antiestrogen, has been shown to be associated with an increased risk of developing hepatic steatosis and non-alcoholic steatohepatitis (NASH) in non-obese female patients with breast cancer.< /p> < p>Understanding the sex-associated difference is necessary to inform the rational design of treatment strategies directed at visceral obese individuals who may develop from hepatic steatosis to cirrhosis and hepatocellular carcinoma.
Keywords: Non-alcoholic fatty liver disease, visceral fat accumulation, hepatic steatosis, NASH, TNF-α, estrogen, adiponectin, leptin, menopause, metabolic syndrome, BMI, obesity, fatty acid β-oxidation
