Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice.

Am J Physiol Regul Integr Comp Physiol 2015 Jan 26;308(2):R131-7. Epub 2014 Nov 26.

Department of Medical and Molecular Genetics, and Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana

Hepatic fatty acid oxidation (FAO) has long been implicated in the control of eating. Nevertheless, direct evidence for a causal relationship between changes in hepatic FAO and changes in food intake is still missing. Here we tested whether increasing hepatic FAO via adenovirus-mediated expression of a mutated form of the key regulatory enzyme of mitochondrial FAO carnitine palmitoyltransferase 1A (CPT1mt), which is active but insensitive to inhibition by malonyl-CoA, affects eating and metabolism in mice. CPT1mt expression increased hepatocellular CPT1 protein levels. This resulted in an increase in circulating ketone body levels in fasted CPT1mt-expressing mice, suggesting an increase in hepatic FAO. These mice did not show any significant changes in cumulative food intake, energy expenditure, or respiratory quotient after 4-h food deprivation. After 24-h food deprivation, however, the CPT1mt-expressing mice displayed increased food intake. Thus expression of CPT1mt in the liver increases hepatic FAO capacity, but does not inhibit eating. Rather, it may even stimulate eating after prolonged food deprivation. These data do not support the hypothesis that an increase in hepatic FAO decreases food intake.

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Source
http://dx.doi.org/10.1152/ajpregu.00279.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297862PMC
January 2015
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