Date of Award

5-2002

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Human Ecology

Major Professor

DiLeep S. Sachan

Committee Members

Edward T. Howley, Naima Moustaid Moussa, Jean D. Skinner

Abstract

Interaction of two nutrients, carnitine and choline, has been reported. Choline supplementation causes a significant conservation of carnitine in normal healthy humans and guinea pigs. The choline supplementation promoted tissue carnitine accretion, particularly in skeletal muscle of guinea pigs, and livers of rats. Also, choline supplemented guinea pigs had lower percentage of carcass fat and higher percentage of protein but the body weights or the respiratory quotient (RQ) were not affected.

Based on these observations, we hypothesized that a combination of choline and carnitine may further increase carnitine accretion by tissues, and if energy needs were increased by exercise and fat mobilization was stimulated by caffeine, there may be reduction in body fat. In other words, simultaneous availability of carnitine, choline, and caffeine may induce mobilization, transport and delivery of fat as the energy substrate of choice, and therefore, enhance utilization of fat. In a 2 x 2 factorial design, male Sprague-Dawley rats were assigned to non-supplemented and supplemented groups and one-half of each group was exercised. Body weight was significantly reduced by exercise only, however, regional fat pad weights and serum leptin concentration were significantly reduced by the combination of carnitine, choline and caffeine supplements as well as by exercise. Regardless of exercise, supplements significantly lowered triglycerides in serum but increased triglycerides in the skeletal muscle.

We postulated that fat loss in rats was due to enhanced fat mobilization and fatty acid oxidation. To support this, we determined the RQ and several metabolic markers of fat oxidation in the rat model. No significant differences were found in the mean RQ values of the groups at rest in all groups and at exhaustion between the two exercised groups. However, increased maximal oxygen uptake (VO2max) and delayed exhaustion time was found in the supplemented rats. Post-exercise concentrations of serum triglycerides were decreased, but β-hydroxybutyrate, acylcarnitine and acetylcarnitine were increased in the supplemented rats. The changes in serum metabolites were complemented by the changes in the muscle and urinary metabolites. The magnitude of increase in urinary acylcarnitine (34 to 45-fold) of the supplemented rats is a unique effect of this combination of the supplements. Evidence indicates enhanced β-oxidation of fatty acids without a change in the RQ because acetyl units were excreted in urine as acetylcarnitine and not oxidized to carbon dioxide. For this phenomenon we proposed the term, "fatty acid dumping".

Finally, we determined fat loss and metabolic effects of this unique nutrient-nutrient interaction in humans. We asked, if the shift in tissue carnitine partitioning will result in enhanced fat oxidation in humans. Healthy adults aged 18-54 y were randomly assigned to a placebo or supplement groups. Supplementary choline and carnitine increased serum concentration of β-hydroxybutyrate. Another biochemical marker of fatty acid oxidation, acetylcarnitine, was elevated about 2-fold and 3-fold in serum and urine, respectively. Short-chain acylcarnitines were moderately elevated in serum but significantly increased in the urine by the supplementation. The observations in humans are consistent with those in rats. This research in rats and humans firmly established that the supplementation with carnitine, choline and caffeine promoted fatty acid oxidation to short-chain fatty acids and their disposal in urine as acylcarnitines.

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