Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin

Abstract

Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipid intermediate ceramide. This study assessed cardiac function, expression of PPAR-regulated genes, and cardiomyocyte apoptosis in rats after 8 wk on either a low-fat diet [normal chow control (NC); 10% fat calories] or high-fat diets composed mainly of either saturated (Sat) or unsaturated fatty acids (Unsat) (60% fat calories) (n = 10/group). The Sat group had lower plasma insulin and leptin concentrations compared with the NC or Unsat groups. Cardiac function and mass and body mass were not different. Cardiac triglyceride content was increased in the Sat and Unsat groups compared with NC (P < 0.05); however, ceramide content was higher in the Sat group compared with the Unsat group (2.9 +/- 0.2 vs. 1.4 +/- 0.2 nmol/g; P < 0.05), whereas the NC group was intermediate (2.3 +/- 0.3 nmol/g). The number of apoptotic myocytes, assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, was higher in the Sat group compared with the Unsat group (0.28 +/- 0.05 vs. 0.17 +/- 0.04 apoptotic cells/1,000 nuclei; P < 0.04) and was positively correlated to ceramide content (P < 0.02). Both high-fat diets increased the myocardial mRNA expression of the PPAR-regulated genes encoding uncoupling protein-3 and pyruvate dehydrogenase kinase-4, but only the Sat diet upregulated medium-chain acyl-CoA dehydrogenase. In conclusion, dietary fatty acid composition affects cardiac ceramide accumulation, cardiomyocyte apoptosis, and expression of PPAR-regulated genes independent of cardiac mass or function.

Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes

“…This may in turn promote ectopic fat storage in nonadipose organs (11). A recent study showed that rats fed a high-saturated fat diet develop smaller epididymal and abdominal fat pads but larger fat deposits in the intrathoracic space (33). This in vivo evidence appears to be in agreement with our hypothesis.…”

Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?

“…Although no significant difference between groups was observed in the FBW, the U-HFD was of sufficient intensity and duration to increase both the total body fat (81.5%) and the adiposity index of U-HFD animals (Table 1) (34,35). These results are in agreement with several studies (28-30) regarding high-saturated-fat-dietinduced obesity that found no difference in FBW.…”

Left Ventricular Mass and Function With Reduced-Fat or Reduced-Carbohydrate Hypocaloric Diets in Overweight and Obese Subjects

“…Excessive saturated fatty acid ingestion coupled with impaired mitochondrial fatty acid oxidation could facilitate ceramide generation, thus promoting cardiomyocyte apoptosis and dysfunction. 25,26 We observed that changes in relative n-3 polyunsaturated fatty acid ingestion predicted changes in LV mass. The observation might suggest a role of n-3 polyunsaturated fatty acids in cardiac remodeling.…”