Making, baking, and breaking: the synthesis, storage, and hydrolysis of neutral lipids.

The esterification of amphiphilic alcohols with fatty acids is a ubiquitous strategy implemented by eukaryotes and some prokaryotes to conserve energy and membrane progenitors and simultaneously detoxify fatty acids and other lipids. This key reaction is performed by at least four evolutionarily unrelated multigene families. The synthesis of this "neutral lipid" leads to the formation of a lipid droplet, which despite the clear selective advantage it confers is also a harbinger of cellular and organismal malaise.

Sterol and diacylglycerol acyltransferase deficiency triggers fatty acid-mediated cell death.

Deletion of the acyltransferases responsible for triglyceride and steryl ester synthesis in Saccharomyces cerevisiae serves as a genetic model of diseases where lipid overload is a component. The yeast mutants lack detectable neutral lipids and cytoplasmic lipid droplets and are strikingly sensitive to unsaturated fatty acids. Expression of human diacylglycerol acyltransferase 2 in the yeast mutants was sufficient to reverse these phenotypes.

The genetics of neutral lipid biosynthesis: an evolutionary perspective.

The storage of fatty acids and fatty alcohols in the form of neutral lipids such as triacylglycerol (TAG), cholesteryl ester (CE), and wax ester (WE) serves to provide reservoirs for membrane formation and maintenance, lipoprotein trafficking, lipid detoxification, evaporation barriers, and fuel in times of stress or nutrient deprivation. This ancient process likely originated in actinomycetes and has persisted in eukaryotes, albeit by different molecular mechanisms. A surfeit of neutral lipids is strongly, perhaps causally, related to several human diseases such as diabetes mellitus, obesity, atherosclerosis and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease: emerging mechanisms and consequences.

Purpose Of Review: One of the critical complications of obesity and diabetes is nonalcoholic fatty liver disease, a disorder of triacylglycerol accumulation in the liver that has potential to develop into end stage liver failure. In this review, the recent progress in understanding the role of hepatic triacylglycerol synthesis in the development of nonalcoholic fatty liver disease is discussed.

Recent Findings: It has become apparent that the development of hepatic steatosis is a complex, multifactorial process.