Regulation of lipid metabolism by carboxylesterases Ces1/Es-x and Ces3/TGH

Excess triacylglycerol (fat) storage is one of the key contributing factors to insulin resistance, type 2 diabetes and cardiovascular disease. A tight regulation between triacylglycerol synthesis, hydrolysis, secretion and fatty acid oxidation is required to prevent lipid accumulation. We are investigating the role of endoplasmic reticulum localized carboxylesterases Ces1/Es-x and Ces3/TGH in lipid metabolism. While Ces1/Es-x-deficient mice develop obesity, hyperlipidemia, fatty liver and insulin resistance, Ces3/TGH-deficient mice have decreased blood lipids, increased insulin sensitivity and are protected from diet-induced hepatic steatosis. The mechanisms by which these related carboxylesterases govern distinct intracellular processes will be discussed.