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Minireview: From Anorexia to Obesity—The Yin and Yang of Body Weight Control

Department of Medicine and Division of Endocrinology (J.M.Z., J.K.E.), and Department of Neurology (J.K.E.), Beth Israel Deaconess Medical Center, and Program in Neuroscience (J.K.E.), Harvard Medical School, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Joel K. Elmquist, D.V.M., Ph.D., 325 Research North, 99 Brookline Avenue, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215. E-mail: jelmquis{at}bidmc.harvard.edu.

Over the past decade, there has been a tremendous increase in the understanding of the molecular and neural mechanisms that control food intake and body weight. Yet eating disorders and cachexia are still common, and obesity cases are rising at alarming rates. Thus, despite recent progress, an increased understanding of the molecular and neural substrates that control body weight homeostasis is a major public health goal. In this review, we discuss the mechanisms by which metabolic signals interact with key behavioral, neuroendocrine, and autonomic regulatory regions of the central nervous system. Additionally, we offer a model in which hormones such as leptin and ghrelin interact with similar central nervous system circuits and engage them in such a way as to maintain an appropriate and tight regulation of body weight and food intake. Our model predicts that overstimulation or understimulation of these central pathways can result in obesity, anorexia, or cachexia.

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