Denis G. Baskin, Ph.D
Metabolism, Endocrinology and Nutrition
Research Professor of Medicine and Biological Structure
My research program focuses on the CNS regulation of food intake, body weight, and energy balance by hormones such as insulin and leptin. These hormones, which are present in blood in direct proportion to body fat mass, have profound anorexic effects when they enter the brain, where they alter the transcription, synthesis, and secretion of peptides (such as neuropeptide Y and melanocortins) in feeding-related neural circuits of the hypothalamus and brainstem.
My research program focuses on the CNS regulation of food intake, body weight, and energy balance by hormones such as insulin and leptin. These hormones, which are present in blood in direct proportion to body fat mass, have profound anorexic effects when they enter the brain, where they alter the transcription, synthesis, and secretion of peptides (such as neuropeptide Y and melanocortins) in feeding-related neural circuits of the hypothalamus and brainstem. Recent work has focused on the interaction of leptin with the satiety action of peptides such as CCK and GLP-1 produced in the intestines during a meal. These gut peptides signal to the brainstem via the vagus nerve and regulate meal size by causing satiety, thereby resulting in meal termination. In the presence of leptin, these satiety signals to the brain are more effective, resulting in smaller meals. We have used immunocytochemistry, situ hybridization, retrograde axonal transport, confocal microscopy, and laser capture microdissection to identify the neuronal cell types, peptide receptors and circuits that participate in regulating meal size by the action of leptin in the hypothalamus and brainstem and, in particular, the interaction of leptin and gut satiety signals to the hindbrain. The goal of this research is to understand brain mechanisms that regulate food intake and body weight and how these mechanisms are altered in diabetes and obesity.
Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG: Central nervous system control of food intake. Nature 404:661-671, 2000.
Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG: Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 143:239-246, 2002.
Niswender KD, Gallis B, Blevins JE, Corson M, Schwartz MW, Baskin DG: Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin. J Histochem Cytochem 51:275-284, 2003.
Blevins JE, Eakin TJ, Murphy JA, Schwartz MW, Baskin DG: Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin. Brain Res 993:30-41, 2003.
Blevins JE, Schwartz MW, Baskin DG: Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brainstem nuclei controlling meal size. Am J Physiol Regul Intger Comp Physiol 287:87-96, 2004.
Morton GJ, Blevins JE, Niswender KD, Gelling RW, Rhodes CJ, Baskin DG, Schwartz MW: Leptin action in the forebrain regulates the hindbrain response to satiety signals: A mechanism linking body fat mass to the control of meal size. J Clin Invest 115:703-710, 2005.
Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW: Central nervous system control of food intake and body weight. Nature 443:289-295, 2006.
Baskin DG: Single-minded view of melanocortin signaling in energy homeostasis. Endocrinology 147:4539-4541, 2006.
Williams DL, Baskin DG, Schwartz MW: Leptin regulation of the anorexic response to glucagon like peptide-1 receptor stimulation. Diabetes 55:3387-3393, 2006.
Williams DL, Schwartz MW, Bastian LS, Blevins JE, Baskin DG: Immunocytochemistry and laser capture microdissection for real time quantitative PCR identify hindbrain neurons activated by interaction between leptin and cholecystokinin. J Histochem Cytochem 52: 285-294, 2008.
Blevins JE, Morton GJ, Williams DL, Caldwell DW, Bastian LS, Wisse BE, Schwartz MW, Baskin DG: Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8. Am J Physiol Regul Integr Comp Physiol 296:R476-R484, 2008.
Baskin DG: In situ Hybridization Using Antibody-Based Methods. In: Society for Neuroscience Shortcourse Manual, Seeing Is Believing: Antibodies and How To Use Them. GE Hoffman, ed, Society for Neuroscience, 2008.
Baskin DG: Elements of the Rationale and Application of Controls for Immunocytochemistry. Chapter 6 In: Principles and Applications of Immunocytochemistry. WL Stahl, DG Baskin eds, The Histochemical Society, 2008.
Williams DL, Baskin DG, Schwartz MW: Evidence that intestinal GLP-1 plays a physiological role in satiety. Endocrinology 150:1680-1687, 2009.
Bastian LS, Baskin DG: Techniques for Immuno-Laser Capture Microscopy of Neurons for Real Time Quantitative PCR. In: Methods in Molecular Biology Volume 115: Immunocytochemical Methods and Protocols. 3rd ed., C Oliver and MC Jamur, eds. Humana Press, in press, 2009.
Blevins JE, Baskin DG: Hypothalamic-Bainstem Circuits Controlling Eating. In: Frontiers in Eating and Weight Regulation. W Langhans and N Geary, eds. S Karger AG, Basel, in press, 2009.
Williams DL, Baskin DG, Schwartz MW: Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin. Am J Physiol Regul Integr Comp Physiol. Sep 2, 2009 [Epub ahead of print].