Prevention of hypertriglyceridemia is one of the biomedical targets in Glycogen Storage Disease type 1a (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 -patients. Plasma 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.
Read more: DOI: 10.1002/jimd.12380
Link to to the paper : https://pubmed.ncbi.nlm.nih.gov/33739445/
Two professors nominated by the University of Groningen have been awarded Royal Decorations on Tuesday 26 April. Professor K.U. Loos is appointed Knight of the Order of the Netherlands Lion. She received this honour from Mayor K. Schuiling at...
Cisca Wijmenga treedt per 1 september 2023 toe tot de Raad van Toezicht van de Hanzehogeschool.
The Board of the University of Groningen has taken note of the Letter to the House of Representatives regarding internationalization in higher education, sent to the House on Friday 21 April by the Minister of Education, Culture and Science Robbert...
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