Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure

Abstract

Abnormalities in energy metabolism may play an important role in the development of hypertensive heart failure. However, the transition from compensated hypertrophy to heart failure is not fully understood in terms of energy metabolism. In Dahl salt-sensitive (DS) and salt-resistant (DR) rats, myocardial fatty acid and glucose uptake values were determined using (131)I- or (125)I-labeled 9-methylpentadecanoic acid ((131)I- or (125)I-9MPA), and [(14)C]deoxyglucose ([(14)C]DG), fatty acid beta-oxidation was identified using thin-layer chromatography, and insulin-stimulated glucose-uptake was observed using a euglycemic hyperinsulinemic glucose clamp. Six-week-old rats were fed a diet that contained 8% NaCl, which resulted in development of compensated hypertrophy in DS rats at 12 wk of age and ultimately led to heart failure by 18 wk of age. Uptake of [(14)C]DG increased markedly with age in the DS rats, whereas (131)I-9MPA uptake was marginally but significantly increased only in animals aged 12 wk. The ratio of (125)I-9MPA beta-oxidation metabolites to total uptake in the DS rats was significantly lower (P < 0.05) at 12 (37%) and 18 (34%) wk compared with at 6 (45%) wk. Insulin increased [(14)C]DG uptake more than twofold in the DS rats at 6 wk, although this increase was markedly attenuated at 12 and 18 wk (11 and 8%, respectively). Our data suggest that in a hypertrophied heart before heart failure, fatty acid oxidation is impaired and the capacity to increase glucose uptake during insulin stimulation is markedly reduced. These changes in both glucose and fatty acid metabolism that occur in association with myocardial hypertrophy may have a pathogenic role in the subsequent development of heart failure.

Ischemic preconditioning accelerates the fatty acid oxidation of rat hearts

“…Recent studies [18,[22][23][24] and the present study, however, clearly demonstrated the existence of cardiac metabolites of methyl-branched fatty acid analogs processed via α-and β-oxidations. As seen in Fig.…”

“…Recent animal studies [18,[22][23][24], however, demonstrated that β-oxidation metabolites of fatty acid analogs with methyl branch, i.e., BMIPP and 9MPA, were detected in coronary venous samples or myocardium, and the amount of β-oxidation metabolites was affected by changes in energy substrate and myocardial disorder. In a metabolic process of BMIPP, α-oxidation is initially required for further metabolic process.…”

High‐fat Diet Prevents Cardiac Hypertrophy and Improves Contractile Function in the Hypertensive Dahl Salt‐sensitive Rat

“…13 The Dahl salt-sensitive rat, a model that develops hypertension and LVH with salt feeding that progresses to heart failure, 14 has reduced fatty acid uptake, which occurs before loss of systolic function. 15,16 This genetic model with dietary trigger does not require surgery to implant an aortic band and results in consistent hypertension and LVH. In the present investigation, we assessed the effect of a highfat diet on LV function and the development of LVH.…”

The Evolving Face of Heart Failure Associated with Elevated Cardio-Metabolic Risk Factors

“…There is evidence that administration of propionyl-L-carnitine increases both glucose and palmitate oxidation in hypertrophied hearts and improves the efficiency of translating ATP production into cardiac work. On this basis, a restoration of metabolic demand by restoring mitochondrial energy efficiency may have potential as a new therapeutic treatment of the hypertensive heart and heart failure (Fujii et al, 2004). Although as yet no agent exists that promote mitochondrial biogenesis, PGC-1 alpha has generated interest.…”