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Low Leptin Levels Play a Role in Re-gaining Weight After Dieting

NEW YORK (July 1, 2008) -- A study by Michael Rosenbaum, M.D., and his colleagues at Columbia University Medical Center has provided new insight into the critical interactions between the fat-derived hormone leptin and the brain in response to weight loss.

With about 90 percent of previously obese individuals regaining their lost weight, Dr. Rosenbaum, working with Rudolph Leibel, M.D., co-director of the Naomi Berrie Diabetes Center at Columbia University, were interested in developing approaches to help individuals maintain a lower body weight, since even modest, sustained weight loss can reduce the risk of type 2 diabetes and heart disease.

Michael Rosenbaum, M.D.	Rudolph Leibel, M.D.

Drs. Rosenbaum and Leibel already knew that leptin levels in blood fall as obese individuals lose weight. The question was whether changes in leptin levels altered activity in the regions of the brain known to have a role in regulating food intake.

The answer is yes, and the results of this study were published in the July 1, 2008 issue of the Journal of Clinical Investigation.

As part of the study, obese individuals were fed liquid diets and reduced their weight by 10 percent. Then, while at the lower body weight, they were given replacement leptin (by injection) or a placebo. At each stage, researchers observed their brain activity in response to food and non-food items.

Using functional Magnetic Resonance Imaging (fMRI) in collaboration with Dr. Joy Hirsch, Ph.D., professor of functional neuroradiology and director of Columbia’s Program for Imaging and Cognitive Sciences (PICS), they observed that activity in these regions of the brain in response to visual food-related cues changed after an obese individual successfully lost weight. However, these changes in brain activity were not observed if the obese individual who had successfully lost weight was treated with leptin. Weight-reduced subjects had more blood flow in areas of the brain that govern emotional and sensory responses to food and less in areas involving control of food intake.

“Weight regain is unfortunately very common following otherwise successful weight reduction. These studies are aimed at determining why,” Dr. Leibel said. “These brain images confirm that the body is subject to powerful biological forces that regulate food intake – forces that are beyond an individual’s conscious control. Obese people who may have struggled to shed 20 pounds will have lower blood levels of leptin that will cause persistent hunger. Combined with reduced energy expenditure – also caused by lower leptin – that’s the perfect storm for re-gaining the weight.”

These findings are almost certainly not limited to the obese; any individual losing weight will be subject to the same responses, Dr. Leibel added. These data are consistent with the idea that leptin evolved primarily as a hormone designed to defend body fat. Body fat is critical to normal reproductive function and to survival in periods of restricted access to food. Why some individuals “defend” higher amounts of body fat is another area of investigation in Dr. Leibel’s group.

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Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree. Among the most selective medical schools in the country, the school is home to the largest medical research enterprise in New York State and one of the largest in the country. For more information, please visit www.cumc.columbia.edu.

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