Fructose Leads to Leptin Resistance and Obesity

Obesity is on the rise worldwide, and poor diet and lack of regular physical activity are often cited as culprits. Residents of many industrialized nations, including the United States, have diets that are high in fat, calories, and sweeteners that lead to overweight and obesity and the related metabolic syndromes. Lately, researchers have focused attention on fructose as an identifiable offender in the obesity epidemic. A new study in rats reveals that fructose may lead to leptin resistance, which, in turn, leads to overweight and obesity.

Fructose is the sugar normally found in fruit, but table sugar and high-fructose corn syrup also contain approximately 50% fructose. These ingredients are common in foods and beverages, and their consumption is more prevalent than ever before. Researchers at the University of Florida published the results of a new study in the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology that revealed high-fructose diets led to leptin resistance in rats, and subsequently triggered weight gain.

Leptin is a hormone that balances food intake with energy expenditure. Normally, the presence of leptin triggers decreased food intake. In a state of leptin resistance, the body does not eat less in the presence of leptin. In this study, rats were fed either fructose-free diets or 60% fructose diets for 6 months, and then tested for leptin resistance. The rats on the high-fructose diet were leptin resistance after 6 months. The same rats also had higher levels of triglycerides in their blood. There were no differences observed between levels of leptin, glucose, cholesterol, or insulin in the two groups of rats. Several studies have already shown that elevated triglycerides impair the transport of leptin to the brain, thereby preventing the brain from responding to the leptin.

Subsequently, the researchers switched half of the rats in each group to a high-fat diet for 2 weeks. The rats that were initially exposed to the high-fructose diet ate more food and gained more weight than the rats that ate a fructose-free diet. The researchers concluded that it is the combination of high-fructose, high-fat, and high-calorie consumption that caused the overweight and obesity epidemic.

Additional rat studies have observed similar results in leptin-resistant rats and leptin therapy has been studied in rats as a way to reduce or reverse dietary weight gain. Notably, many studies have found that a combination of exercise and leptin therapy is the most viable anti-obesity treatment.

The researchers of the most recent study plan to perform additional studies to determine if the leptin resistance in rats is reversible in the absence of a high-fructose diet. Also, human studies are needed to determine if these results can be generalized for the human population. Still, there is little argument that most diets are not as healthy as they could be. Fructose may now be one more key to unlocking the secret of healthy, balanced diets.


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Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol. Nov 2008;295(5):R1370-1375.

Jennifer Gibson, PharmD

Jennifer Gibson, PharmD, is a practicing clinical pharmacist and medical writer/editor with experience in researching and preparing scientific publications, developing public relations materials, creating educational resources and presentations, and editing technical manuscripts. She is the owner of Excalibur Scientific, LLC.
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