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Here, we demonstrate that decreased left ventricular contractile function in male, but not female, HCM mice is associated with reduced fatty acid translocase (CD36) and AMP\u2010activated protein kinase (AMPK) activity. As a result, the levels of myocardial ATP and triglyceride (TG) content are reduced, while the levels of oleic acid and TG in circulating very low density lipoproteins (VLDLs) and liver are increased. With time, these metabolic changes culminate in enhanced glucose production in male HCM mice. Remarkably, restoration of ventricular TG and ATP deficits via AMPK agonism as well as inhibition of gluconeogenesis improves ventricular architecture and function. These data underscore the importance of the systemic effects of a primary genetic heart disease to other organs and provide insight into potentially novel therapeutic interventions for HCM.<\/jats:p>","DOI":"10.1002\/emmm.201302852","type":"journal-article","created":{"date-parts":[[2014,2,24]],"date-time":"2014-02-24T15:09:28Z","timestamp":1393254568000},"page":"482-495","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Metabolic crosstalk between the heart and liver impacts familial hypertrophic cardiomyopathy"],"prefix":"10.1038","volume":"6","author":[{"given":"Jason A","family":"Magida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie A","family":"Leinwand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,2,24]]},"reference":[{"key":"BFEMMM201302852_CR1","doi-asserted-by":"crossref","first-page":"E331","DOI":"10.1152\/ajpendo.00298.2002","volume":"284","author":"AS Augustus","year":"2003","unstructured":"Augustus AS, Kako Y, Yagyu H, Goldberg IJ (2003) Routes of FA delivery to cardiac muscle: modulation of lipoprotein lipolysis alters uptake of TG\u2010derived FA. 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