Fatty acid sources and their fluxes as they contribute to plasma triglyceride concentrations and fatty liver in humans.

Abstract

Different sources of fatty acids (FA) used for VLDL-triglyceride synthesis include dietary FA that clear to the liver via chylomicron uptake, FA synthesized de novo in the liver from carbohydrates, nonesterified fatty acids derived from adipose tissue, nonesterified fatty acids derived from the spillover of chylomicron-triglyceride in the fasted and fed states, and FA stored in liver lipid droplets. Data have amassed on the contributions of each of these sources to liver-triglyceride accrual, VLDL-triglyceride synthesis, and hypertriglyceridemia. Discussed here is the timing of use of FA from each of these sources for synthesis of VLDL-triglyceride. Secondly, as all of these FA sources have been shown to contribute significantly to nonalcoholic fatty liver disease (NAFLD), data are presented demonstrating how poor handling of FA and glucose in the periphery can contribute to NAFLD. Lastly, we highlight how the stress of excess FA availability on the liver can be corrected by reduction of dietary intake of sugars and fats, weight loss, and increased physical activity. A better understanding of how lifestyle factors improve FA flux will aid in the development of improved treatments for the devastating condition of NAFLD.