Shift in metabolic fuel in acylation-stimulating protein-deficient mice following a high-fat diet.

P. Schrauwen, E. Moonen Kornips, J. St Onge, M.K. Hesselink, D. Richard, D.R. Joanisse, K. Cianflone*

*Corresponding author for this work

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    ASP-deficient mice (C3KO) have delayed postprandial TG clearance, are hyperphagic and display increased energy expenditure. Markers of carbohydrate and fatty acid metabolism in the skeletal muscle and heart were examined to evaluate the mechanism. On a high-fat diet, when compared to wildtype (WT) mice, C3KO mice have increased energy expenditure, decreased RQ, lower ex vivo glucose oxidation (- 39%, p=0.0181) and higher ex vivo fatty acid oxidation (+68%, p= 0,019). They have, lower muscle glycogen content (-25%, P<0.05) and lower activities for the following glycolytic enzymes: glycogen phosphorylase (-31%, p=0.005), hexokinase (-43%, p=0.007), phosphofructokinase (-51%, P<0.0001) and glyceraldehyde-3-phosphate dehydrogenase (-15%, p=0.04). Analysis of mitochondrial enzyme activities revealed that hydroxyacyl-coenzyme A dehydrogenase was higher (+25%, p=0.004) in C3KO mice. Furthermore, Western blot analysis of muscle revealed significantly higher fatty acid transporter CD36 (+40%, p=0.006) and cytochrome C (a marker of mitochondrial content) (+69%, p=0.034) levels in C3KO mice, while the activity of AMP kinase (AMPK) was lower (-48%, p=0.0029). Overall, these results demonstrate a shift in the metabolic potential of skeletal muscle toward increased fatty acid utilization. Whether this is a consequence of (i) decreased adipose tissue storage with repartitioning towards muscle or (ii) a direct result of the absence of ASP interaction with the receptor C5L2 in muscle, remains to be determined. However, these in vivo data suggest that ASP inhibition could be a potentially viable approach in correcting muscle metabolic dysfunction in obesity. Key words: ASP, muscle metabolism, glycolysis, high-fat diet, b-oxidation.
    Original languageEnglish
    Pages (from-to)E1015-E1019
    JournalAmerican Journal of Physiology : Endocrinology and Metabolism
    Issue number6
    Publication statusPublished - 1 Jan 2008


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