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April 21, 2004

Fat Cell Hormone Adiponectin Causes
Weight Loss Without Affecting Appetite

Penn Discovery Opens up Potential for Future Therapy to Tackle Obesity

(Philadelphia, PA) - Researchers at the University of Pennsylvania School of Medicine have established in an animal model that the hormone adiponectin secreted by fat tissue acts in the brain to reduce body weight. In contrast to leptin, a related hormone, adiponectin can cause weight loss by raising metabolic rate while not affecting appetite. This finding may have future implications in understanding and treating obesity and metabolic disorders like diabetes, says lead author, Rexford Ahima, MD, PhD, Assistant Professor of Medicine, Penn Diabetes Center. This research appears in the May issue of Nature Medicine.

When adiponectin, which is involved in glucose and lipid metabolism, was introduced into the cerebrospinal fluid of normal mice, they showed no changes in food intake, but their metabolism rose. “The animal burns off more heat, so over time loses weight, which was very fascinating because we knew that leptin caused weight loss by suppressing appetite and increasing metabolic rate,” explains Ahima. “Here we have another fat hormone that can cause weight loss but without affecting intake.”

For many dieters, it’s easy, at first, to lose weight; but over time, it becomes more difficult because the body compensates, in part, by dropping its metabolic rate. “Adiponectin or its targets in the brain and other organs could be harnessed to sustain weight loss by maintaining a high metabolic rate,” says Ahima. “This is only a possibility. We’re not suggesting at this point that adiponectin will become a drug.” In severely obese mice, adiponectin rapidly decreases blood glucose and lipids, while burning fat. Hence, adiponectin could be beneficial in the treatment of diabetes and heart disease associated with obesity.

These findings have far-reaching potential to help fight the war against obesity, which healthcare experts agree has reached epidemic proportions in the United States. “For years people used to think fat tissue was a passive player--just there to store excess energy,” explains Ahima. This proved to be a simplistic view since hormones produced by fat tissue are released into the blood and are actively involved in the regulation of metabolism. The best known fat hormone, leptin, decreases body weight by decreasing appetite and increasing metabolic rate. Leptin also reduces glucose and lipids. The researchers found that both adiponectin and leptin require the melanocortin pathway in the brain to control body weight and glucose. However, these fat hormones also control metabolism through other distinct pathways in the brain. “We focus on the brain because it is a major coordinator of feeding, metabolism, and hormones, including insulin,” says Ahima.

Other Penn researchers collaborating on this work are Yong Qi, Nobuhiko Takahashi, and Hiralben R. Patel, as well as Philipp E. Scherer, Anders Berg, and Utpal B. Pajvani from the Albert Einstein College of Medicine and Stanley M. Hileman from West Virginia University. The research is funded by grants from the National Institutes of Health.

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PENN Medicine is a $2.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation’s first integrated academic health system).

Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System consists of four hospitals (including its flagship Hospital of the University of Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report), a faculty practice plan, a primary-care provider network, three multispecialty satellite facilities, and home health care and hospice.



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