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Joshua Thaler And Chongren Tang, Diabetes & Obesity Center Faculty

Joshua Thaler, M.D., Ph.D.

Metabolism, Endocrinology & Nutrition

Assistant Professor of Medicine


Focus

My focus is the hypothalamic regulation of energy homeostasis and the alterations to this system during obesity pathogenesis. My primary project investigates hypothalamic inflammation and its relationship to high fat diet-induced weight gain with an emphasis on the role of glial cells (astrocytes and microglia) in modulating the neuronal regulation of energy homeostasis. In particular, we are determining whether glial cells provide a repair response to diet-induced damage to critical hypothalamic neurons and whether interventions targeted at glia may therefore influence the course of obesity. A second study examines the role of inflammatory signaling in hypothalamic neurons and microglia in obesity-associated insulin resistance and diabetes.

Research Interest

My focus is the hypothalamic regulation of energy homeostasis and the alterations to this system during obesity pathogenesis.  My primary project investigates hypothalamic inflammation and its relationship to high fat diet-induced weight gain with an emphasis on  the role of glial cells (astrocytes and microglia) in modulating the neuronal regulation of energy homeostasis.  In particular, we are determining whether glial cells provide a repair response to diet-induced damage to critical hypothalamic neurons and whether interventions targeted at glia may therefore influence the course of obesity.  A second study examines the role of inflammatory signaling in hypothalamic neurons and microglia in obesity-associated insulin resistance and diabetes.

Publications

Kim F, Pham M, Luttrell I, Bannerman DD, Tupper J, Thaler J, Hawn TR, Raines EW, Schwartz MW.  Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity.  Circ Res 100:1589-1596, 2007.

Thaler JP, Choi SJ, Sajan MP, Ogimoto K, Nguyen HT, Matsen M, Benoit SC, Wisse BE, Farese RV, Schwartz MW.  Atypical protein kinase C activity in the hypothalamus is required for lipopolysaccharide-mediated sickness responses.  Endocrinology. 150:5362-5372, 2009.

Thaler JP, Choi SJ, Schwartz MW, Wisse BE. Hypothalamic Inflammation and Energy Homeostasis: Resolving the Paradox.  Frontiers in Neuroendocrinology. 31:79-84, 2010.

Sarruf DA, Thaler JP, Morton GJ, German J, Fischer JD, Ogimoto K, Schwartz MW. Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats. Diabetes. 59:1817-1824, 2010.

Oh-I S*, Thaler JP*, Ogimoto K, Wisse BE, Morton GJ, Schwartz MW.  Central administration of interleukin-4 exacerbates hypothalamic and weight gain during high-fat feeding. Am J Physiol Endocrinol Metab. 299:E47-53, 2010.

German JP, Wisse BE, Thaler JP, Oh-I S, Sarruf DA, Ogimoto K, Kaiyala KJ, Fischer JD, Matsen ME, Taborsky GJ Jr, Schwartz MW, Morton GJ.  Leptin deficiency causes insulin resistance induced by uncontrolled diabetes.  59:1626-1634, 2010.

Thaler JP, Schwartz MW. Inflammation and obesity pathogenesis: the hypothalamus heats up.  Endocrinology. 2010 Jun 23

German JP, Thaler JP, Wisse BE, Oh-I S, Sarruf DA, Matsen ME, Fischer JD, Taborsky GJ Jr, Schwartz MW, Morton GJ.  Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 152:394-404, 2011.

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, and Schwartz MW. Obesity is Associated with Hypothalamic Injury in Rodent Models and Humans.  J Clin Invest, 122(1):153–162, 2012.