Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism

Abstract

Pathological cardiac hypertrophy leads to derangements in lipid metabolism that may contribute to the development of cardiac dysfunction. Since previous studies, using high saturated fat diets, have yielded inconclusive results, we investigated whether provision of a high-unsaturated fatty acid (HUFA) diet was sufficient to restore impaired lipid metabolism and normalize diastolic dysfunction in the pathologically hypertrophied heart. Male, Wistar rats were subjected to supra-valvar aortic stenosis (SVAS) or sham surgery. After 6 weeks, diastolic dysfunction and pathological hypertrophy was confirmed and both sham and SVAS rats were treated with either normolipidic or HUFA diet. At 18 weeks post-surgery, the HUFA diet failed to normalize decreased E/A ratios or attenuate measures of cardiac hypertrophy in SVAS animals. Enzymatic activity assays and gene expression analysis showed that both normolipidic and HUFA-fed hypertrophied hearts had similar increases in glycolytic enzyme activity and down-regulation of fatty acid oxidation genes. Mass spectrometry analysis revealed depletion of unsaturated fatty acids, primarily linoleate and oleate, within the endogenous lipid pools of normolipidic SVAS hearts. The HUFA diet did not restore linoleate or oleate in the cardiac lipid pools, but did maintain body weight and adipose mass in SVAS animals. Overall, these results suggest that, in addition to decreased fatty acid oxidation, aberrant unsaturated fatty acid metabolism may be a maladaptive signature of the pathologically hypertrophied heart. The HUFA diet is insufficient to reverse metabolic remodeling, diastolic dysfunction, or pathologically hypertrophy, possibly do to preferentially partitioning of unsaturated fatty acids to adipose tissue.

Pharmacokinetic and metabolomic analyses of Mangiferin calcium salt in rat models of type 2 diabetes and non-alcoholic fatty liver disease

“…Caprylic acid, suberic acid and 3-oxooctanoic acid are important unsaturated fatty acids in the body. They regulate metabolism and cell signal transduction in the body, participate in the synthesis, decomposition and metabolism of fatty acids, and are converted into acetyl-CoA through beta oxidation into the citric acid cycle [ 44 , 45 ]. Vaccenyl carnitine is a long-chain acyl fatty acid derivative of carnitine.…”

The Cardiac Lipidome in Models of Cardiovascular Disease

“…The study reported decreases in unsaturated (oleic and linoleic) free fatty acids as well as diacylglycerol and triacylglycerol molecules in SVAS heart tissue. However, the HUFA diet did not restore these lipids to normal levels [70]. In one model, mice on a PUFA diet had impaired wound healing post-MI [71].…”

Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload

“…There are several experimental models for studying CR, one being the pressure overload model (4)(5)(6)(7)(8)(9)(10)(11)(12). Pulmonary artery stenosis (7,8), abdominal aortic stenosis (9,10), and supravalvar aortic stenosis (AoS) (1,3,5,6) are examples of interventions used to study this condition.…”

“…Pulmonary artery stenosis (7,8), abdominal aortic stenosis (9,10), and supravalvar aortic stenosis (AoS) (1,3,5,6) are examples of interventions used to study this condition. AoS has been used to promote the gradual development of left ventricular hypertrophy in young rats (1,3,5,6), with the effects appearing as weeks go by (3,5,11,12).…”

“…Regarding heart dysfunction, echocardiogram studies by our research group found that 18 weeks after AoS induction, rats develop left atrium (LA) remodeling, concentric left ventricular hypertrophy, diastolic dysfunction, and systolic function maintenance, improvement, or dysfunction (1,12).…”