Impaired Very-Low-Density Lipoprotein catabolism links hypoglycemia to hypertriglyceridemia in Glycogen Storage Disease type Ia. 2021

Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Prevention of hypertriglyceridemia is one of the biomedical targets in Glycogen Storage Disease type Ia (GSD Ia) patients, yet it is unclear how hypoglycemia links to plasma triglyceride (TG) levels. We analyzed whole-body TG metabolism in normoglycemic (fed) and hypoglycemic (fasted) hepatocyte-specific glucose-6-phosphatase deficient (L-G6pc-/- ) mice. De novo fatty acid synthesis contributed substantially to hepatic TG accumulation in normoglycemic L-G6pc-/- mice. In hypoglycemic conditions, enhanced adipose tissue lipolysis was the main driver of liver steatosis, supported by elevated free fatty acid concentrations in GSD Ia mice and GSD Ia patients. Plasma very-low-density lipoprotein (VLDL) levels were increased in GSD Ia patients and in normoglycemic L-G6pc-/- mice, and further elevated in hypoglycemic L-G6pc-/- mice. VLDL-TG secretion rates were doubled in normo- and hypoglycemic L-G6pc-/- mice, while VLDL-TG catabolism was selectively inhibited in hypoglycemic L-G6pc-/- mice. In conclusion, fasting-induced hypoglycemia in L-G6pc-/- mice promotes adipose tissue lipolysis and arrests VLDL catabolism. This mechanism likely contributes to aggravated liver steatosis and dyslipidemia in GSD Ia patients with poor glycemic control and may explain clinical heterogeneity in hypertriglyceridemia between GSD Ia patients.

UI MeSH Term Description Entries
D007003 Hypoglycemia A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH. Fasting Hypoglycemia,Postabsorptive Hypoglycemia,Postprandial Hypoglycemia,Reactive Hypoglycemia,Hypoglycemia, Fasting,Hypoglycemia, Postabsorptive,Hypoglycemia, Postprandial,Hypoglycemia, Reactive
D008079 Lipoproteins, VLDL A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues. Pre-beta-Lipoprotein,Prebeta-Lipoprotein,Prebeta-Lipoproteins,Very Low Density Lipoprotein,Very-Low-Density Lipoprotein,Very-Low-Density Lipoproteins,Lipoprotein VLDL II,Lipoproteins, VLDL I,Lipoproteins, VLDL III,Lipoproteins, VLDL1,Lipoproteins, VLDL2,Lipoproteins, VLDL3,Pre-beta-Lipoproteins,Lipoprotein, Very-Low-Density,Lipoproteins, Very-Low-Density,Pre beta Lipoprotein,Pre beta Lipoproteins,Prebeta Lipoprotein,Prebeta Lipoproteins,VLDL Lipoproteins,VLDL1 Lipoproteins,VLDL2 Lipoproteins,VLDL3 Lipoproteins,Very Low Density Lipoproteins
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005234 Fatty Liver Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS. Liver Steatosis,Steatohepatitis,Steatosis of Liver,Visceral Steatosis,Liver Steatoses,Liver, Fatty,Steatohepatitides,Steatoses, Liver,Steatoses, Visceral,Steatosis, Liver,Steatosis, Visceral,Visceral Steatoses
D005260 Female Females
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D005952 Glucose-6-Phosphatase An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9. Glucosephosphatase,Glucose 6-Phosphatase,Glucose-6-Phosphate Phosphohydrolase,Glucose 6 Phosphatase
D005953 Glycogen Storage Disease Type I An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood. Glucose-6-Phosphatase Deficiency,Glucosephosphatase Deficiency,Glycogenosis 1,Hepatorenal Glycogen Storage Disease,von Gierke Disease,Deficiency, Glucosephosphatase,Gierke Disease,Gierke's Disease,Glycogen Storage Disease 1 (GSD I),von Gierke's Disease,Deficiencies, Glucose-6-Phosphatase,Deficiencies, Glucosephosphatase,Deficiency, Glucose-6-Phosphatase,Disease, Gierke,Disease, Gierke's,Disease, von Gierke,Disease, von Gierke's,Gierkes Disease,Glucose 6 Phosphatase Deficiency,Glucose-6-Phosphatase Deficiencies,Glucosephosphatase Deficiencies,von Gierkes Disease

Related Publications

Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
October 2001, Journal of inherited metabolic disease,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
April 1985, Metabolism: clinical and experimental,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
September 1978, Metabolism: clinical and experimental,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
May 2020, Journal of pediatric endocrinology & metabolism : JPEM,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
January 2013, Genetics in medicine : official journal of the American College of Medical Genetics,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
December 1995, The Journal of clinical investigation,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
April 1989, The American journal of physiology,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
June 2008, American journal of obstetrics and gynecology,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
June 2022, Molecular genetics and metabolism reports,
Joanne A Hoogerland, and Fabian Peeks, and Brenda S Hijmans, and Justina C Wolters, and Sander Kooijman, and Trijnie Bos, and Aycha Bleeker, and Theo H van Dijk, and Henk Wolters, and Albert Gerding, and Karen van Eunen, and Rick Havinga, and Amanda C M Pronk, and Patrick C N Rensen, and Gilles Mithieux, and Fabienne Rajas, and Folkert Kuipers, and Dirk-Jan Reijngoud, and Terry G J Derks, and Maaike H Oosterveer
January 2001, Journal of gastroenterology,
Copied contents to your clipboard!