Although glyceroneogenesis was first found in adipose tissues, it was not recognized in the liver until 1998.  This finding was unexpected because triglyceride synthesis in the liver was thought not to occur due to the amount of gluconeogenesis taking place, and because the liver was believed to have sufficient glycerol 3-phosphate collected from the bloodstream. Several experiments using stable isotopes to track the glycerol in the liver and bloodstream, showed that 65% of the glycerol backbone of triglycerides in the bloodstream is synthesized in the liver. It was subsequently found that the liver synthesizes more than half of the glycerol mammals need to regulate lipids.
Glyceroneogenesis in the liver and adipose tissues regulate lipid metabolism in opposite ways. Lipids as triglycerides are released from the liver, while glyceroneogenesis restrains the fatty acid release from adipose tissues by re-esterifying them. When the lipid concentration in the blood is relatively high, glyceroneogenesis in the liver will be down-regulated to stop the synthesis of triglycerides, but glyceroneogenesis in adipose tissues will be induced in order to restrain the release of free fatty acid to the bloodstream. Conversely, glyceroneogenesis is induced in the liver and suppressed in adipose tissues when the blood lipid level is low. Although the reciprocal regulation of glyceroneogenesis is not well understood, a hormone called glucocorticoid is involved in the regulation. Glucocorticoids induce gene transcription of PEPC-K in liver but repress the transcription in adipose tissues.