The present model is useful in that fat-fed rats do not develop increased body weight or visceral adiposity, hypertriglyceridemia, or systemic insulin resistance [3],

allowing for examination of diet effects in the absence of these modulators of myocardial structure and function. Selleckchem Birinapant The absence of conventional comorbidities is probably due to similar energy intake and feed efficiency across groups, attributed to the large amount of dietary fat in both high-fat diets and resultant reduced intake by weight. Furthermore, compared with CON and WES animals, WES + DHA rats had greater circulating adiponectin, an adipokine associated with antihypertrophic effects [32], [33] and [34]. The lack of improvement in WES diet-associated gross LVH with supplemental

DHA, together with the diet effect on myocyte cross sectional area and circulating adiponectin, led us to consider whether the diets were associated with genotypic DNA Damage inhibitor variation distinguishing an adaptive vs maladaptive myocardial response. Our results indicate that Wistar rats develop surprisingly few differences in myocardial gene expression, despite the interaction effect of diet and blood pressure previously observed in this strain. Of the 3 possible group comparisons, the CON vs WES dietary groups surprisingly revealed the least genotypic variance. No canonical or toxicologic pathway was strongly represented; the ratio of DEG:total pathway genes did not exceed 0.038. Following is a more detailed discussion of represented pathways and functions relevant to acquired nonischemic cardiomyopathy initially identified in results, with a focus on those specific to the WES vs WES + DHA groups, identified as the principle comparison of the study. Of canonical pathways, the ILK signaling pathway was represented. Mice with

cardiac ILK deletion developed dilated cardiomyopathy, systolic dysfunction, fibrosis, and myocyte disarray [23]. Actin cytoskeleton signaling was also identified as differentially represented in WES and WES + DHA rats. Cytoskeletal function is critical to cell stabilization, Phospholipase D1 signal transduction, and myocardial contraction; disruption of this system is a known contributor to an array of hypertrophic and dilative cardiomyopathic responses [35], and evidence suggests that modulation of the actin cytoskeleton may be a mechanism of leptin-associated myocardial remodeling [24]. The cytokine IL-9 was also identified as relevant to the WES vs WES + DHA comparison; circulating levels are increased in association with cardiomyopathy and heart failure [25] and [26]. Of the cardiomyopathy-associated toxicologic pathways differentially represented in WES and WES + DHA groups, p53 signaling emerged.