期刊
DIABETES OBESITY & METABOLISM
卷 16, 期 8, 页码 757-760出版社
WILEY-BLACKWELL
DOI: 10.1111/dom.12248
关键词
observational study; carnitine palmitoyltransferase; fatty acid oxidation; cardiac hypertrophy
资金
- COBRE center grant from the National Institutes of Health [NIH 8 P20-GM103528]
- NORC center grant from the National Institutes of Health [NIH 2P30-DK072476]
- ADA [1-10-BS-129]
- NIH [R01DK089641, R01DK098687]
Recent reports suggest that short-term pharmacological carnitine palmitoyltransferase 1 (Cpt1) inhibition improves skeletal muscle glucose tolerance and insulin sensitivity. Although this appears promising for the treatment of diabetes, these Cpt1 inhibitors are not specific to skeletal muscle and target multiple Cpt1 isoforms. To assess the effects of inhibiting the Cpt1b isoform we generated mice with a heart-and skeletal muscle-specific deletion of the Cpt1b, Cpt1b(HM-/-). These mice seem to develop normally with similar bodyweights as control mice. However, premature mortality was observed by 15weeks of age in the Cpt1b(HM-/-)mice. The hearts of Cpt1bHM-/-mice were four times the size of controls. Cpt1b(HM-/-)mice were also subject to stress-induced seizures that accompanied an increased risk for premature mortality. Our data suggests that prolonged Cpt1b inhibition poses severe cardiac risk and emphasizes that attempts to improve insulin sensitivity by targeting Cpt1 with current inhibitors is not viable.
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