ANN ARBOR, Mich. - As we all know from experience, people eat not only because they are hungry, but also because the food just simply tastes too good to pass up.
Now, a new study by the University of Michigan Health System helps to explain how leptin, a hormone produced by fat tissue, influences that motivation to eat.
The researchers describe for the first time a new bunch of leptin-responsive neurons that feed into the dopamine system located in the ventral tegmental area, a part of the brain that controls the rewarding properties we assign to things.
"These neurons and their downstream targets represent the site of action for drugs of abuse, and also control motivation for food, sex or a fancy car," says Martin Myers, Jr.,Ph.D., an associate professor of internal medicine at the U-M Medical School, and Marilyn H. Vincent Professor of Diabetes Research at the Michigan Comprehensive Diabetes Center.
The study in the August issue of Cell Metabolism
adds to growing evidence that leptin doesn't turn the appetite on and off just by controlling satiety - for instance, whether we feel hungry or full.
Most who have studied leptin in the brain have focused on an important circuit in the arcuate nucleus, called the ARC, an area in the brain's hypothalamus that controls energy balance by controlling satiety.
"It has been assumed that leptin action in the ARC - if not the be-all and end-all - was responsible for the vast majority of leptin's effect on appetite," says Myers whose lab at U-M focuses on the impact of leptin on diabetes and metabolic syndrome.
But in fact, neurons bearing leptin receptors exist in many other parts of the brain too. The new findings show that leptin also has direct effects on the lateral hypothalamic area, or LHA, which in turn exerts greater influence on the dopamine system.
The new study shows that leptin injected in the LHA part of the brain of rats causes the animals to eat less and lose weight. Leptin action in the LHA also raises dopamine content in the brains of otherwise leptin-deficient animals.
While in general higher dopamine release tends to be associated with wanting things - food or something else - Myers said he suspects the higher dopamine at baseline may in fact dampen the response to food temptations, making them easier to resist.
"Some people may overeat rewarding food because of a perceived 'reward deficit', " Myers suggests. "When leptin is turned up, it might fix that deficit and make us feel better about a lot of things."
It's not yet clear how the leptin-responsive neurons in the LHA and VTA work together to control dopamine and with it, our motivations, according to the study.
"In the future, it will be crucial to address the potential dysregulation of these neurons in states of obesity," Myers says.
Additional authors: Gina M. Leinninger, Ph.D., research fellow at the U-M Medical School, Ann Arbor, Mich.; Young-Hwan Jo, Albert Einstein College of Medicine, Bronx, NY; Rebecca L. Leshan, graduate student, U-M Medical School; Gwendolyn W. Louis, graduate student, U-M Medical School; Hongyan Yang, U-M Medical School; Jason G. Barrera, University of Cincinnati, Cincinnati, Ohio; Hilary Wilson, University of Cincinnati; Darren M. Opland, graduate student U-M Medical School; Miro A. Faouzi, U-M Medical School; Yusong Gong, U-M Medical School; Justin C. Jones, research associate, U-M Medical School; Christopher J. Rhodes, University of Chicago; Streamson Chua, Jr., Albert Einstein College of Medicine; Sabrina Diano, Yale University, New Haven, Conn.; Tamas L. Horvath, Yale University, U-M Medical School, Randy J. Seeley, U-M Medical School, Jill B. Becker, U-M Medical School and Heike Munzberg, Ph.D. research assistant professor U-M Medical School.
Funding: Michigan Diabetes Research and Training Center; Michigan Comprehensive Diabetes Center and grants from the American Diabetes Association, American Heart Association, National Institutes of Health and the Obesity Society.
Reference: Cell Metabolism, Vol. 10, Issue 2, 6 August, 2009.