Improved energy homeostasis of the heart in the metabolic state of exercise

Abstract

We postulate that metabolic conditions that develop systemically during exercise (high blood lactate and high nonesterified fatty acids) are favorable for energy homeostasis of the heart during contractile stimulation. We used working rat hearts perfused at physiological workload and levels of the major energy substrates and compared the metabolic and contractile responses to an acute low-to-high work transition under resting versus exercising systemic metabolic conditions (low vs. high lactate and nonesterified fatty acids in the perfusate). Glycogen preservation, resulting from better maintenance of high-energy phosphates, was a consequence of improved energy homeostasis with high fat and lactate. We explained the result by tighter coupling between workload and total beta-oxidation. Total fatty acid oxidation with high fat and lactate reflected increased availability of exogenous and endogenous fats for respiration, as evidenced by increased long-chain fatty acyl-CoA esters (LCFA-CoAs) and by an increased contribution of triglycerides to total beta-oxidation. Triglyceride turnover (synthesis and degradation) also appeared to increase. Elevated LCFA-CoAs caused high total beta-oxidation despite increased malonyl-CoA. The resulting bottleneck at mitochondrial uptake of LCFA-CoAs stimulated triglyceride synthesis. Our results suggest the following. First, both malonyl-CoA and LCFA-CoAs determine total fatty acid oxidation in heart. Second, concomitant stimulation of peripheral glycolysis and lipolysis should improve cardiac energy homeostasis during exercise. We speculate that high lactate contributes to the salutary effect by bypassing the glycolytic block imposed by fatty acids, acting as an anaplerotic substrate necessary for high tricarbocylic acid cycle flux from fatty acid-derived acetyl-CoA.

Upregulation of the Cardiac Monocarboxylate Transporter MCT1 in a Rat Model of Congestive Heart Failure

“…Thus, because lactate bypasses the glycolysis, it functions as a major anaplerotic substance in addition to providing ATP and allows tight metabolic control of the energy metabolism in the cell. 26 Pyruvate, which is transported by MCT1, can also have this effect. 27 Pyruvate increases the strength of contraction by increasing the Ca 2ϩ load of the sarcoplasmic reticulum.…”

Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction

“…In light of this, one also must consider pyruvate (derived from glycolysis) and/or α-ketoglutarate (derived from glutaminolysis) as anaplerotic substrates for efficient Krebs cycle use of fatty acidderived acetyl CoA (9), suggesting the possibility that in certain cell types, high rates of aerobic glycolysis and/or glutaminolysis may promote efficient FAO (i.e., fats burn in the fire of carbohydrates; ref. 10).…”

Relação entre a administração de esteróide anabólico androgênico, treinamento físico aeróbio e supercompensação do glicogênio

“…It is known that the high blood concentrations of fatty acids and lactate diminish cardiac glycogen oxidation, thus saving the use of this substrate (33) . As the trained animals treated with AAS or vehicle presented a lower triglyceride blood concentration, probably as a result of the degradation of this substrate used during exercise, it is believed that the blood concentration of fatty acids probably increased.…”