The factor Nrf2 mediates antioxidant responses, and when down-regulated is associated with heart failure

and unmitigated afterload-induced oxidative stress [29]. Cardiac hypertrophy also emerged as a toxicologic process differentially represented in WES and WES + DHA groups. Also relevant to these 2 treatment groups, biological functions pertinent to acquired nonischemic cardiomyopathy included cardiovascular disease and organismal injury and abnormalities. In contrast to the present study, others demonstrated remarkable genotypic and phenotypic aberration with WES and high-fat diet intake but in the presence of comorbidities that are known to be associated with myocardial hypertrophy (ie, increased body weight, hypertension, and insulin resistance) [7],

[36] and [37]. LGK-974 mw Collectively, these data support the idea that diet, unaccompanied by changes in body morphometry, hemodynamics, or metabolic aberrancy, may be a minor determinant in the development of obesity-induced cardiomyopathy. A previous study using cultured neonatal rat cardiomyocytes treated with eicosapentaenoic acid and DHA revealed 122 DEGs (FC, ≥0.51), 47 of which the authors were able to identify [10]. In the present in vivo study, the WES + DHA vs CON dietary Pictilisib ic50 groups revealed the largest number of DEGs. Following is a brief discussion of 4 differentially expressed factors relevant to either nutritional/metabolic aberrancy or cardiovascular system disease/function pathways that were validated by qRT-PCR and WB and altered by WES + DHA intake. Retinol saturase (all-trans-retinol 13,14-reductase) encodes an enzyme that is localized to membranes and expressed primarily in adipose, liver, kidney, and intestinal tissue [38] and [39] but has also been identified in myocardial tissue. [40] The enzyme catalyzes the

saturation of all-trans-retinol to form all-trans-13,14-dihydroretinol. [38] In vitro studies suggest that the enzyme promotes adipocyte differentiation in a peroxisome proliferator-activated receptor (PPARγ)-dependent manner. Thymidine kinase [39] About obesity, adipose Retsat messenger RNA (mRNA) is reduced in both genetic and dietary murine models as well as in obese humans, an effect partly attributed to suppression by infiltrating macrophages [39]. In the present study, myocardial Retsat gene expression was reduced in rats fed the WES diet compared with CON animals and increased with DHA supplementation. Consistent with this, myocardial inflammation is enhanced with WES diet intake [41] and attenuated by DHA [42]. In contrast to gene expression, however, RETSAT protein expression was highest in WES-fed rats, suggesting that gene and protein expression may be differentially regulated by diet and/or inflammation.