Docosahexaenoic Acid Supplementation Does Not Improve Western Diet-Induced Cardiomyopathy in Rats

Abstract

Obesity increases risk for cardiomyopathy in the absence of hypertension, diabetes or ischemia. The fatty acid milieu, modulated by diet, may modify myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy. We sought to identify gross, cellular and ultrastructural myocardial changes associated with Western diet intake, and subsequent modification with docosahexaenoic acid (DHA) supplementation. Wistar and Sprague-Dawley (SD) rats received 1 of 3 diets: control (CON); Western (WES); Western + DHA (WES+DHA). After 12 weeks of treatment, echocardiography was performed and myocardial adiponectin, fatty acids, collagen, area occupied by lipid and myocytes, and ultrastructure were determined. Strain effects included higher serum adiponectin in Wistar rats, and differences in myocardial fatty acid composition. Diet effects were evident in that both WES and WES+DHA feeding were associated with similarly increased left ventricular (LV) diastolic cranial wall thickness (LVWcr/d) and decreased diastolic internal diameter (LVIDd), compared to CON. Unexpectedly, WES+DHA feeding was associated additionally with increased thickness of the LV cranial wall during systole (LVWcr/s) and the caudal wall during diastole (LVWca/d) compared to CON; this was observed concomitantly with increased serum and myocardial adiponectin. Diastolic dysfunction was present in WES+DHA rats compared to both WES and CON. Myocyte cross sectional area (CSA) was greater in WES compared to CON rats. In both fat-fed groups, transmission electron microscopy (TEM) revealed myofibril degeneration, disorganized mitochondrial cristae, lipid inclusions and vacuolation. In the absence of hypertension and whole body insulin resistance, WES+DHA intake was associated with more global LV thickening and with diastolic dysfunction, compared to WES feeding alone. Myocyte hypertrophy, possibly related to subcellular injury, is an early change that may contribute to gross hypertrophy. Strain differences in adipokines and myocardial fatty acid accretion may underlie heterogeneous data from rodent studies.

Dietary fatty acids alter left ventricular myocardial gene expression in Wistar rats

“…Previously reported gas chromatography data confirm that dietary DHA was incorporated into the phospholipid fraction of myocardial septal tissue (CON 13.79 ± 0.49 area %, WES 10.82 ± 0.43 area %, WES+DHA 31.64 ± 0.50 area %; p<0.0001). [3]…”

“…[3] We previously reported that WES and WES+DHA feeding were associated with similarly increased LV cranial wall thickness and decreased LV internal diameter during diastole, compared to CON animals. [3] 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. 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.…”

“…A previously reported dietary study includes information regarding animals, dietary treatments, anesthesia and tissue collection;[3] brief summaries are provided below. Left ventricular tissue samples used in the present work were taken from a subset of Wistar rats from this previously reported dietary study examining the effect of diet and strain (Sprague Dawley and Wistar).…”

“…Intake of a “Western” diet rich in saturated fatty acids and simple carbohydrates is associated with left ventricular hypertrophy and diastolic dysfunction. [1–3] In contrast, consumption of n-3 polyunsaturated fatty acids (PUFA) is associated with antihypertrophic effects. [4–7] We were therefore surprised to observe that rats fed a Western diet supplemented with docosahexaenoic acid (DHA) for three months had similar thickening of the cranial LV wall compared to rats fed a Western diet alone, and had increased caudal LV wall thickness compared to control animals.…”

“…[4–7] We were therefore surprised to observe that rats fed a Western diet supplemented with docosahexaenoic acid (DHA) for three months had similar thickening of the cranial LV wall compared to rats fed a Western diet alone, and had increased caudal LV wall thickness compared to control animals. [3] These findings led us to consider whether the underlying genotype of the myocardial tissue differed despite a similar gross phenotype; that is, whether Western diet consumption promoted a pathologic or maladaptive gene expression profile, while DHA treatment was associated with physiologic or adaptive gene expression.…”