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Hepatic Glycerol Shunt and Glycerol-3-phosphate Phosphatase Control Liver Metabolism and Glucodetoxification Under Hyperglycemia by Anfal Al-Mass; Pegah Poursharifi; Marie-Line Peyot; Roxane Lussier; Isabelle Chenier; Yat Hei Leung; Anindya Ghosh; Abel Oppong; Elite Possik; Yves Mugabo; Rasheed Ahmad; Robert Sladek; S.R. Murthy Madiraju; Fahd Al-Mulla; Marc Prentki is a Medicine article available to read on EtoBox.

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## Objective Glycerol-3-phosphate (Gro3P) phosphatase (G3PP) hydrolyzes Gro3P to glycerol that exits the cell, thereby operating a “glycerol shunt”, a metabolic pathway that we identified recently in mammalian cells. We have investigated the role of G3PP and the glycerol shunt in the regulation of glucose metabolism and lipogenesis in mouse liver. ## Methods We generated hepatocyte-specific G3PP-KO mice (LKO), by injecting AAV8-TBG-i__Cre__ to male G3PP^fl/fl^ mice. Controls received AAV8-TBG-__eGFP.__ Both groups were fed chow diet for 10 weeks. Hyperglycemia (16–20 mM) was induced by glucose infusion for 55 h. Hepatocytes were isolated from normoglycemic mice for __ex vivo__ studies and targeted metabolomics were measured in mice liver after glucose infusion. ## Results LKO mice showed no change in body weight, food intake, fed and fasted glycemia but had increased fed plasma triglycerides. Hepatic glucose production from glycerol was increased in fasted LKO mice. LKO mouse hepatocytes displayed reduced glycerol production, elevated triglyceride and lactate production at high glucose concentration. Hyperglycemia in LKO mice led to increased liver weight and accumulation of trigly

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Author

Anfal Al-Mass; Pegah Poursharifi; Marie-Line Peyot; Roxane Lussier; Isabelle Chenier; Yat Hei Leung; Anindya Ghosh; Abel Oppong; Elite Possik; Yves Mugabo; Rasheed Ahmad; Robert Sladek; S.R. Murthy Madiraju; Fahd Al-Mulla; Marc Prentki

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Medicine (Health Sciences)