Glyceroneogenesis revisited.
Glyceroneogenesis is the synthesis of 3-glycerol phosphate by an abbreviated version of gluconeogenesis. The research that led to the discovery of glyceroneogenesis in white adipose tissue is presented. This pathway is active during fasting in white and brown adipose tissue and in the liver as part of the triglyceride/fatty acid cycle. Glyceroneogenesis is critical for the extensive recycling of free fatty acid (FFA) back to triglyceride that occurs in mammals, including humans, after lipolysis, when up to 65% of the fatty acids are re-esterified back to triglyceride. The rate-limiting enzyme in this pathway is the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (4.1.1.32) (PEPCK-C). Transcription of this gene is induced in adipose tissue and liver during fasting. Ablation of expression of the gene for PEPCK-C in white adipose tissue of mice results in lipodsytrophy, while overexpression of the gene for this enzyme in adipose tissue causes obesity. The critical role of glyceroneogenesis in diabetes was suggested by experiments in which the gene for PEPCK-C is induced in white adipose tissue by rosiglitazone, a drug used to control diabetes in humans. This was accompanied by a marked decrease in FFA release from adipose tissue due to an induction in glyceroneogenesis in the tissue. Since the chronic release of FFA by adipose tissue is a critical factor in the development Type 2 diabetes, it is likely that rosiglitazone acts in part by stimulating transcription of the gene for PEPCK-C, thereby increasing rate of glyceroneogenesis and lowering the rate of FFA release from adipose tissue.
Hanson
Richard W
RW
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-3945, USA. rwh@po.cwru.edu
Reshef
Lea
L
D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism*
D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005990:Glycerol