Triheptanoin-enriched diet attenuates hypertrophy and preserves diastolic function and cardiac glucose oxidation in rats with pressure overload

Objectives: Pressure-overload (PO) induced hypertrophy is characterized by altered anaplerosis of the Krebs-cycle which is linked to impaired glucose oxidation (GO). Triheptanoin delivers odd-chain fatty acids which can support anaplerosis by providing the Krebs-cycle with propionyl-CoA. We evaluated the effects of a triheptanoin-enriched diet on cardiac function and GO in rats with PO.

Methods: Sprague-Dawley rats underwent aortic banding (AoB) to induce PO. Starting at 1 week after AoB, rats were fed a control or special diets containing triheptanoin at 17% (T17-group) or 30% (T30-group) of caloric requirement. We assessed ventricular hypertrophy and function echocardiographically. Cardiac power and oxidation rates of glucose and fatty acids were measured by isolated working heart perfusion. Plasma levels of b-hydroxypentanoate (BHP) were determined by mass spectrometry as therapy monitoring.

Results: *: p < 0.05

6 weeks after AoB, the T30-group presented significantly lower left ventricular mass index (5.6 ± 0.4 vs. 7.2 ± 0.5 mg/g;*) and lower ratio of transmitral to mitral annular early diastolic velocity E/e' (11.1 ± 1 vs. 15.5 ± 1.4;*) compared to those of controls, indicating reduced hypertrophy and improved diastolic function, respectively. Cardiac power and fatty acid oxidation were similar among groups. However, rates of GO were significantly higher in the T30-group compared to those of the T17-group and controls (0.76 ± 0.1 vs. 0.46 ± 0.08 or 0.41 ± 0.03µmol/min/gdry;*) and directly proportional to plasma BHP levels (r = 0.83; p < 0.001).

Conclusions: Triheptanoin treatment reduces hypertrophy and improves diastolic function and cardiac GO in rats with PO. The results suggest targeting anaplerotic supplementation to approach pathological hypertrophy.