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Fat rats reveal why short-term overeating can lead to obesity and diabetes

Date:
March 13, 2006
Source:
Journal of Clinical Investigation
Summary:
In a study appearing online on March 9 in advance of print publication in the April issue of the JCI, Luciano Rossetti and colleagues at Albert Einstein College of Medicine in New York report that overeating in normal rats on a lard-based diet is inhibited when ribozymes are used to block liver carnitine palmitoyltransferase-1 (CPT1A) activity. Critically, the treatment also improved blood sugar levels and insulin resistance, suggesting that CPT1A antagonists may improve insulin resistance.
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Obesity is due to a mismatch between the number of calories we consume and the amount of physical activity we undertake. In the brain, a region called the hypothalamus control ours eating behavior through its metabolism of fat molecules called fatty acids. Interestingly, eating too much in the short-term can result in a severe drop in the ability of the body (and brain) to be satisfied by fat and to control blood sugar levels.

In a study appearing online on March 9 in advance of print publication in the April issue of the Journal of Clinical Investigation, Luciano Rossetti and colleagues at Albert Einstein College of Medicine in New York report that inhibiting an enzyme in the liver called carnitine palmitoyltransferase-1 (CPT1A), which is involved in metabolizing fatty acids, inhibits feeding.

The researchers placed normal rats on a lard-based diet, which stimulated the animals to voluntarily overeat and gain weight. When the researchers inhibited CPT1A by delivering special molecules called "ribozymes" into the brain of the rats, the animals ate dramatically less.

The treatment also improved the blood sugar levels of these animals, who suffered from a common metabolic impairment known as insulin resistance, in which the body is unable to respond properly to insulin. The authors report that this animal model of diet-induced obesity and insulin resistance displayed defective adaptation to an increase in fat availability coupled with a severe impairment in the ability of the brain to sense fat intake.

Further studies will be required to establish the critical role of this biochemical pathway in nutrient sensing in other animal models and, critically, in humans.



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Journal of Clinical Investigation. "Fat rats reveal why short-term overeating can lead to obesity and diabetes." ScienceDaily. ScienceDaily, 13 March 2006. <www.sciencedaily.com/releases/2006/03/060312214643.htm>.
Journal of Clinical Investigation. (2006, March 13). Fat rats reveal why short-term overeating can lead to obesity and diabetes. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2006/03/060312214643.htm
Journal of Clinical Investigation. "Fat rats reveal why short-term overeating can lead to obesity and diabetes." ScienceDaily. www.sciencedaily.com/releases/2006/03/060312214643.htm (accessed May 23, 2017).

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