To determine whether preexisting differences in fat oxidation might contribute to individual susceptibility to diet-induced obesity, Friedman and lead author Hong Ji used rats that differ in their genetic predisposition to gain weight and become obese when fed a high-fat diet.
The closely-related strains weigh the same and eat the same amount of calories when fed a low-fat diet. However, when switched to a high-fat diet, the strain that is obesity-prone overeats and becomes obese, while the obesity-resistant strain does not.
The researchers found that even when eating a low-fat diet and still lean, the obesity-prone rats were less able to burn fat than were the obesity-resistant rats. This intrinsic deficit in fat oxidation was associated with a decrease in the capacity to make two liver enzymes. One, CD36, is responsible for transferring fat fuels into liver cells, while the second enzyme, acyl-coenzyme A dehydrogenase, begins the oxidation process in mitochondria.
When fed a high-fat diet, the obesity-prone rats overate and became obese, gaining 36% more weight than resistant animals. Fat oxidation was further compromised due to a decreased ability to make CPT1A, the liver enzyme responsible for transporting fat into mitochondria.
The inherited propensity to gain weight when eating a high-fat diet appears to be due to a preexisting limit on the ability to burn fat in the liver. This defect persists during the development of obesity and is then further compounded by additional deficits in the fat oxidizing machinery, comments Friedman.
Other studies in Friedmans laboratory have demonstrated that a decrease in fat oxidation and energy production in the liver generates a signal that stimulates eating. Experiments in his and other laboratories have also found that treatments that increase fat oxidation reduce food intake and cause we
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Contact: Leslie Stein
stein@monell.org
267-519-4707
Monell Chemical Senses Center
24-Jul-2007