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SUMMARY:DEFICIENT FATTY ACID OXIDATION CAUSES FASTING INDUCED HYPOGLYCMIA\
 , HYPOTHERMIA AND HEPATIC GLYCOGEN DEPLETION
DTSTART:20101123T160000
DTSTAMP:20260510T062917Z
UID:de5ade171664384fe268eb438b8c90f449f9766ed55192ab746cdb30
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr. Sander M. HOUTEN\nIntroduction. Mitochondrial fatty acid 
 β-oxidation (FAO) is the major pathway for degradation of dietary fatty a
 cids. FAO is essential to maintain energy homeostasis in liver and heart a
 nd is of particular importance during fasting. FAO is catalyzed by a serie
 s of enzymes\, for most of which inherited defects in man have been descri
 bed. The main pathological consequences associated with FAO defects are hy
 poketotic 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.\nMethods. Body temperature was measured using an implanta
 ble\, programmable\, temperature transponder. Glucose uptake was quantifie
 d using 2-[14C(U)]-deoxy-D-glucose.\nResults. Previously\, we demonstrated
  that fasted LCAD KO mice have mild hypoketotic hypoglycemia due to increa
 sed metabolic clearance rate and decreased endogenous production of glucos
 e. Glucose uptake is specifically increased in oxidative tissues such as h
 eart (27-fold) and soleus muscle (5-fold). De novo gluconeogenesis is not 
 impaired\, but hepatic glycogen stores are virtually depleted. As a conseq
 uence\, fasted LCAD KO mice have no hyperglycemic response to glucagon inj
 ection. The decreased endogenous glucose production in combination with de
 ficient FAO leads to a low energetic state\, as evidenced by a progressive
  hypothermia during fasting.\nConclusion. A defect in FAO is primarily com
 pensated by increased glucose use at the expense of hypoglycemia\, hypothe
 rmia and glycogen depletion. Fasted LCAD KO mice have an impaired flight-o
 r-fight response.
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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