Abstract
Glyceroneogenesis and the Triglyceride/Fatty Acid Cycle
Highlights
During fasting in all mammals, triglyceride stored in adipose tissue is hydrolyzed by a hormone-sensitive lipase to produce free fatty acids (FFA)1 and glycerol
What is the metabolic source of glyceride-glycerol needed to support the triglyceride/fatty acid cycle? There are three major possibilities: glucose, via glycolysis, glycerol after phosphorylation by glycerol kinase, or the conversion of pyruvate to glycerideglycerol via a pathway to be discussed, termed glyceroneogenesis
The discovery of this pathway resulted from our finding that white adipose tissue (WAT) contains both pyruvate carboxylase and the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) [10], two enzymes thought at the time to be involved only in gluconeogenesis
Summary
More than 30 years ago we [10, 11] and others [12] described a pathway for the re-esterification of FFA during fasting in WAT that involved the generation of 3-glycerol phosphate from precursors other than glucose. In the initial studies that established the existence of the pathway of glyceroneogenesis, we demonstrated that the addition of pyruvate to rat epididymal adipose tissue, incubated in vitro, reduced FFA release by ϳ65%, while not altering lipolysis (as determined by the amount of glycerol released into the medium) because of increased FFA re-esterification [11, 15, 16] These findings suggested a potential physiological role for glyceroneogenesis in the re-esterification of FFA in WAT during fasting, thereby controlling both the release of FFA and subsequently ketogenesis [11]. Modifying the expression of the gene for PEPCK-C is critical because this enzyme, This paper is available on line at http://www.jbc.org
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