Hepatocyte-Specific Expression of Human Carboxylesterase 1 Attenuates Diet-Induced Steatohepatitis and Hyperlipidemia in Mice.

Rodents have at least five carboxylesterase 1 () genes, whereas there is only one gene in humans, raising the question as to whether human and mouse genes share the same functions. In this study, we investigate the role of human CES1 in the development of steatohepatitis or dyslipidemia in C57BL/6 mice. Hepatocyte-specific expression of human CES1 prevented Western diet or alcohol-induced steatohepatitis and hyperlipidemia.

Bile Acid Biology, Pathophysiology, and Therapeutics.

http://aasldpubs.onlinelibrary.wiley.

Lipocalin-2 Protects Against Diet-Induced Nonalcoholic Fatty Liver Disease by Targeting Hepatocytes.

Hepatocytes are the major source of hepatic lipocalin-2 (LCN2), which is up-regulated in response to inflammation, injury, or metabolic stress. So far, the role of hepatocyte-derived LCN2 in the development of nonalcoholic fatty liver disease (NAFLD) remains unknown. Herein we show that overexpression of human LCN2 in hepatocytes protects against high fat/high cholesterol/high fructose (HFCF) diet-induced liver steatosis and nonalcoholic steatohepatitis by promoting lipolysis and fatty acid oxidation (FAO) and inhibiting lipogenesis (DNL), lipid peroxidation, and apoptosis.

Deficiency of cholesterol 7α-hydroxylase in bile acid synthesis exacerbates alcohol-induced liver injury in mice.

Alcoholic fatty liver disease (AFLD) is a major risk factor for cirrhosis-associated liver diseases. Studies demonstrate that alcohol increases serum bile acids in humans and rodents. AFLD has been linked to cholestasis, although the physiologic relevance of increased bile acids in AFLD and the underlying mechanism of increasing the bile acid pool by alcohol feeding are still unclear.