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/
Achieving more together: Joint strategy paper of the Universities of Oldenburg and Groningen - Cooperation partners adopt new 2020-2030 Roadmap with seven core fields of collaboration
The rapid testing pilot project in the higher and vocational educational sectors in Groningen will be expanded. Two new locations will be joining the pilot project: one at the Euroborg for Noorderpoort students, and the other in the Wiebenga...
The Dutch Research Council (NWO) has awarded Prof. Lude Franke a Vici grant worth € 1.5 million. The Vici grant will enable him to develop innovative lines of research for the next five years. Vici is one of the largest personal academic grants...
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