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baskin

Denis G. Baskin, Ph.D

Metabolism, Endocrinology and Nutrition

Research Professor of Medicine and Biological Structure


Focus

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.


Research Interest

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.



Publications

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.

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.

Niswender KD, Baskin DG, Schwartz MW: Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endo. Metab 15:362-369,  2004.

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.

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.

Niswender KD, Baskin DG, Schwartz MW: Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis. Trends Endo. Metab 15:362-369,  2004.

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, and 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.

Porte D Jr, Baskin DG, Schwartz MW: Insulin Signaling in the Central Nervous System: A critical role in metabolic homeostasis and disease from C. elegans to man. Diabetes 54:1264-1276, 2005.

Morton GJ, Cummings DE, Baskin DG, Barsh GSand 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, 55:3387-93, 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. Nov 2007 (Epub ahead of print), 52: 285-294, 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. In: Principles and Applications of Immunocytochemistry. The Histochemical Society, 2008.

Williams DL, Baskin DG, Schwartz MW: Evidence that intestinal GLP-1 plays a physiological role in satiety. Endocrinology [Epub ahead of print Dec 12, 2008] 150:1680-1687, 2009.

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. Dec 24. [Epub ahead of print] Dec 24, 2008] 296:R476-84, 2009.

Williams DL, Baskin DG, Schwartz MW: Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin. Am J Physiol Regul Integr Comp Physiol 297:R1238-46, 2009.

Baskin DG, Bastian LS: Techniques for immuno-laser capture microscopy of neurons for real time quantitative PCR. Method in Mol Biol 588:219-230, 2010.

Blevins JE, Baskin DG: Hypothalamic-brainstem circuits controlling eating. Forum Nutr. [Epub 2009 Nov 27] 63:133-140, 2010.

Baskin DG, Kim F, Gelling RW, Russell BJ, Schwartz MW, Morton GJ, Simham HM, Moralejo DH, Blevins JE: A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology, 151(9):4207-13, 2010.

Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V,   Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW, Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122:153-62, 2012. Epub 2011 Dec 27.

Schwartz MW, Baskin DG: Leptin and the brain: then and now. J Clin Invest 123(6):2344-5, 2013. Epub 2013 Jun 3. PMID: 23722910; PMCID: PMC3668840.

Ho JM, Anekonda VT, Thompson BW, Zhu M, Curry RW, Hwang BH, Morton GJ, Schwartz MW, Baskin DG, Appleyard SM, Blevins JE: Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on food intake in male rats. Endocrinology. 2014 May 30:en20141148. [Epub ahead of print] PubMed PMID: 24877632.

Baskin DG: Cell and Tissue Fixation and Processing. In: Pathobiology of Human disease: An Encyclopedia of Disease Mechanisms, Part 4, Techniques in Experimental Pathology| Section 4: Immunohistochemistry. K Roth, ed., Elsevier (in press)

Baskin DG: Leptin interaction with brain orexigenic and anorexigenic pathways. In: Leptin-Regulation and Clinical Applications, Chapter 3. S Dagogo-Jack, ed., NY, Springer (in press)

Hewitt SM, Baskin DG, Frevert CW, Stahl WL, Rosa-Molinar E: Controls for Immunohistochemistry: The Histochemical Society’s Standards of Practice for Validation of Immunohistochemical Assays. J Histochem Cytochem (in press).