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 calories, 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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Journal
Nature Medicine