Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.

E-GEOD-37546 - Disturbed Hepatic Carbohydrate Management During High Metabolic Demand in Medium-Chain Acyl-CoA Dehydrogenase (MCAD)-deficient Mice

Released on 25 April 2012, last updated on 27 June 2012
Mus musculus
Samples (20)
Array (1)
Protocols (7)
Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD-/- mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD-/- mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1a (Pgc-1a) and decreased peroxisome proliferator-activated receptor alpha (Ppar a) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD-/- mice in both conditions,suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD-/- mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD-/- mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD-/- mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD-/- mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD-/- mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. Total RNA obtained from Liver ( 20 samples) , where comparing 4 groups, consisting out of 5 biological replicates, all groups where fasted for 12 hrs, and half of them where injected with LPS ( 100ug/20gr BW) or vehicle
Experiment type
transcription profiling by array 
vincent bloks <>, A Gerding, DJ Reijngoud, F Kuipers, G P Smit, H Herrema, M Muller, R Havinga, T G Derks, T H van Dijk, U J Tietge, V W Bloks
Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice. Herrema H, Derks TG, van Dijk TH, Bloks VW, Gerding A, Havinga R, Tietge UJ, Müller M, Smit GP, Kuipers F, Reijngoud DJ. , PMID:18459129
Investigation descriptionE-GEOD-37546.idf.txt
Sample and data relationshipE-GEOD-37546.sdrf.txt
Raw data (1)
Processed data (1)
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-37546.eSet.r