| Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling. | |
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MedLine Citation:
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PMID: 23376793 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Exogenous dietary fat can induce obesity and promote diabetes, but endogenous fat production is not thought to affect skeletal muscle insulin resistance, an antecedent of metabolic disease. Unexpectedly, the lipogenic enzyme fatty acid synthase (FAS) was increased in the skeletal muscle of mice with diet-induced obesity and insulin resistance. Skeletal muscle-specific inactivation of FAS protected mice from insulin resistance without altering adiposity, specific inflammatory mediators of insulin signaling, or skeletal muscle levels of diacylglycerol or ceramide. Increased insulin sensitivity despite high-fat feeding was driven by activation of AMPK without affecting AMP content or the AMP/ATP ratio in resting skeletal muscle. AMPK was induced by elevated cytosolic calcium caused by impaired sarco/endoplasmic reticulum calcium ATPase (SERCA) activity due to altered phospholipid composition of the sarcoplasmic reticulum (SR), but came at the expense of decreased muscle strength. Thus, inhibition of skeletal muscle FAS prevents obesity-associated diabetes in mice, but also causes muscle weakness, which suggests that mammals have retained the capacity for lipogenesis in muscle to preserve physical performance in the setting of disrupted metabolic homeostasis. |
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Authors:
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Katsuhiko Funai; Haowei Song; Li Yin; Irfan J Lodhi; Xiaochao Wei; Jun Yoshino; Trey Coleman; Clay F Semenkovich |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-2-8 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: - ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-2-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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