Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis

Copy number variation in the carboxylesterase 1 gene and the risk of non-alcoholic fatty liver in a Chinese Han population-a case control study

“…A recent study showed that the expression of CES1 correlated positively with increased lipid storage and the plasma lipid concentration, and attenuation of human CES1 activity was beneficial for hepatic lipid metabolism. The mechanism was determined to include decreased very-low density lipoprotein secretion, decreased expression of hepatic lipogenic genes, and increased fatty acid oxidation [27].…”

Intestinal Lipolysis Mitigates Nonalcoholic Fatty Liver Disease: New Roles for Carboxylesterase 2c in the Intestine

“…Although dyslipidemia is a hallmark of NAFLD, the mechanisms through which aberrant lipogenesis contributes to NAFLD are not fully understood. (3) Both genetic and environmental factors are associated with NAFLD development. Genetic factors include specific genotypes (PNPLA3, TM6SF2, and GCKR), which have been found to predict NASH and severe liver disease, but have no significant connection to type 2 diabetes.…”

“…(6) Regardless of phenotype, a critical histological and metabolic feature of NAFLD is the accumulation of TG in the liver, which when in excess can lead to hepatic steatosis, which may further promote cell death, inflammation, and hepatic stellate cell activation, developing NASH and fibrosis. (3,7) More recent literature has implicated carboxylesterases in NAFLD and obesity. Specific roles include regulation of both TG pools for very low density lipoprotein synthesis, the size and number of cytosolic lipid droplets, as well as the impact on blood fatty acid concentration and insulin sensitivity.…”

“…Although dyslipidemia is a hallmark of NAFLD, the mechanisms through which aberrant lipogenesis contributes to NAFLD are not fully understood . Both genetic and environmental factors are associated with NAFLD development.…”

“…Insulin resistance holds the critical mechanistic function of impairing insulin action, resulting in up‐regulation of hepatic de novo lipogenesis and triglyceride (TG) synthesis, and increased fatty acid delivery to the liver . Regardless of phenotype, a critical histological and metabolic feature of NAFLD is the accumulation of TG in the liver, which when in excess can lead to hepatic steatosis, which may further promote cell death, inflammation, and hepatic stellate cell activation, developing NASH and fibrosis . More recent literature has implicated carboxylesterases in NAFLD and obesity.…”