DEFICIENT FATTY ACID OXIDATION CAUSES FASTING INDUCED HYPOGLYCMIA, HYPOTHERMIA AND HEPATIC GLYCOGEN DEPLETION
Event details
| Date | 23.11.2010 |
| Hour | 16:00 |
| Speaker | Dr. Sander M. HOUTEN |
| Location | |
| Category | Conferences - Seminars |
Introduction. Mitochondrial fatty acid β-oxidation (FAO) is the major pathway for degradation of dietary fatty acids. FAO is essential to maintain energy homeostasis in liver and heart and is of particular importance during fasting. FAO is catalyzed by a series of enzymes, for most of which inherited defects in man have been described. The main pathological consequences associated with FAO defects are hypoketotic hypoglycemia, and skeletal- and cardiac myopathy. Mouse models are useful to study the pathophysiology and to test different therapeutic approaches. In this study, we used the long chain acyl-CoA dehydrogenase (LCAD) KO mouse.
Methods. Body temperature was measured using an implantable, programmable, temperature transponder. Glucose uptake was quantified using 2-[14C(U)]-deoxy-D-glucose.
Results. Previously, we demonstrated that fasted LCAD KO mice have mild hypoketotic hypoglycemia due to increased metabolic clearance rate and decreased endogenous production of glucose. Glucose uptake is specifically increased in oxidative tissues such as heart (27-fold) and soleus muscle (5-fold). De novo gluconeogenesis is not impaired, but hepatic glycogen stores are virtually depleted. As a consequence, fasted LCAD KO mice have no hyperglycemic response to glucagon injection. The decreased endogenous glucose production in combination with deficient FAO leads to a low energetic state, as evidenced by a progressive hypothermia during fasting.
Conclusion. A defect in FAO is primarily compensated by increased glucose use at the expense of hypoglycemia, hypothermia and glycogen depletion. Fasted LCAD KO mice have an impaired flight-or-fight response.
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Practical information
- General public
- Free
Contact
- Lab. Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands