Our Research: Faculty/Research Laboratories

Gregory J. Morton, PhD

Research Associate Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition

Email Address: gjmorton@u.washington.edu

Division of Metabolism, Endocrinology and Nutrition Website:  http://depts.washington.edu/metab/

Background:

Greg Morton received his PhD at Deakin University in Geelong, Australia in 2000.  He then completed his post-doctoral fellowship training in the laboratory of Dr. Michael Schwartz within the Division of Metabolism, Endocrinology and Nutrition at the University of Washington, Seattle and is currently a Research Associate Professor of Medicine at the Diabetes and Obesity Center of Excellence at the University of Washington.

Focus:

Dr. Morton’s research focuses on studying the role of the brain in the regulation of energy balance and glucose metabolism.  Specifically, his research centers on the action of the adiposity signals, insulin and leptin in the hypothalamus and examines the mechanisms and pathways by which they mediate their effects on energy balance and glucose metabolism using physiological, molecular biological, pharmacological and histochemical approaches.

CNS Leptin Normalizes Blood Glucose Levels in T1D without Insulin

The brain was suggested to play an important role in the control of blood glucose based on observations made by the renowned physiologist, Claude Bernard back in the 19th century.  However, ever since the discovery of insulin in the 1921, and the subsequent demonstration that insulin action in peripheral tissues such as liver, muscle and adipose tissue accounts for most aspects of insulin-mediated glucose metabolism, interest shifted away from the brain as a regulator of glucose homeostasis.  Although insulin remains the cornerstone of therapy for type 1 diabetes (T1D) in humans, recent evidence suggests that pharmacological administration of leptin systemically can also normalize blood glucose levels in rodent models of uncontrolled, insulin-deficient diabetes (uDM).  We and others implicate the brain in this effect and demonstrate that continuous intracerebroventricular (icv) infusion of a low dose of leptin normalizes blood glucose levels in rats with uDM via a mechanism that is independent of reduced food intake, increased urinary glucose loss, or recovery of pancreatic beta-cells. Instead, leptin activates a previously unrecognized, insulin-independent mechanism for potently inhibiting hepatic glucose production (HGP), while increasing tissue glucose utilization.  Our overarching goal is to identify specific neuronal subsets downstream of leptin action that link communication between the brain and peripheral tissues in the control of glucose metabolism.

Representative Publications:

Morton GJ, Thatcher BS, Reidelberger RD, Ogimoto K, Wolden-Hanson TH, Baskin DG, Schwartz MW and Blevins JE.  Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab. 2012 Jan;302(1):E134-44.

German JP, Thaler JP, Wisse BE, Shinsuke Oh-I, Sarruf DA, Fischer JD, Matsen ME, Taborsky Jr, GJ, Schwartz MW and Morton GJ.  Leptin activates a novel CNS mechanism for insulin-independent normalization of severe diabetic hyperglycemia. Endocrinology 2011 Feb; 152(2):394-404. PMCID: PMC3037161.

German JP, Wisse BE, Thaler JP, Shinsuke Oh-I, Sarruf DA, Fischer JD, Matsen ME, Taborsky Jr, GJ, Schwartz MW and Morton GJ.  Leptin deficiency causes insulin resistance induced by uncontrolled diabetes.  Diabetes. 2010 Jul;59(7):1626-34. PMCID: PMC2889761.

German J, Kim F, Schwartz GJ, Havel PJ, Rhodes CJ, Schwartz MW, Morton GJ. Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology. 2009 Oct;150(10):4502-11.

Morton, G.J., Gelling, R.W., Niswender, K.D., Morrison, C.D., Rhodes, C.J., and Schwartz, M.W. Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2:411-420, 2005.

  • Kaiyala KJ, Morton GJ, Thaler JP, Meekt TH, Tylee T, Ogimoto K, Wisse BE.  Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice. PLoS One. 2012;7(8):e41473. PMCID: PMC3425585.

    Thaler JP, Yi, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf SA, 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 rodents and humans. J Clin Invest 2012 Jan 3;122(1):153-62. PMCID: PMC3248304.

    Cummings BP, Bettaieb A, Graham JL, Stanhope KL, Dill R, Morton GJ, Jah FG and Havel PJ. Subcutaneous administration of leptin normalizes fasting plasma glucose in obese type 2 diabetic UCD-T2DM rats.  Proc. Natl. Acad. Sci. USA. 2011 Aug 30; 108(35):14670-5. PMCID: PMC3167517.

    Morton GJ, Kaiyala KJ, Fischer JD, Ogimoto K, Schwartz MW and Wisse BE. Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice.  Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E392-401.  PMCID: PMC3043625.

    Sarruf DA, Thaler JP, Morton GJ, German J, Fischer JD, Ogimoto K and Schwartz MW.  FGF21 acts in the brain to increase energy expenditure and insulin sensitivity. Diabetes 2010 Jul;59(7):1817-24. PMCID: PMC2889784.

    Shinsuke Oh-I, Thaler JP, Ogimoto K, Wisse BE, Morton GJ and Schwartz MW.  Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high fat feeding. Am J Physiol Endocrinol Metab. 2010 Jul; 299(1):E47-53. PMCID: PMC2904047.

    Kaiyala KJ, Morton GJ, Leroux B, Ogimoto K and Schwartz MW.  Relative contributions of fat and lean mass to murine metabolic rate. Diabetes 2010 Jul;59(7):1657-66. PMCID: PMC2889765.

    Ellacott KLJ, Morton GJ, Woods SC, Tso P and Schwartz MW.  Assessment of feeding behavior in laboratory mice. Cell Metabolism. 2010 Jul 4; 12(1):10-7. PMCID: PMC2916675 .

    Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S., and Schwartz, M.W. Central nervous system control of food intake and body weight. Nature. 443:289-295, 2006.

    Gelling, R.W., Morton, G.J., Morrison, C.D., Niswender, K.D., Myers, M.G., Jr., Rhodes, C.J., and Schwartz, M.W. Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metab. 3:67-73, 2006.

    Morton, G.J., Blevins, J.E., Williams, D.L., Niswender, K.D., Gelling, R.W., Rhodes, C.J., Baskin, D.G., and Schwartz, M.W. Leptin action in the forebrain regulates the hindbrain response to satiety signals. J Clin Invest. 115:703-710, 2005.

    Morton, G.J., Mystkowski, P., Matsumoto, A.M., and Schwartz, M.W. Increased hypothalamic melanin concentrating hormone gene expression during energy restriction involves a melanocortin-independent, estrogen-sensitive mechanism. Peptides. 25:667-674, 2004.

    Morton, G.J., Niswender, K.D., Rhodes, C.J., Myers, M.G., Jr., Blevins, J.E., Baskin, D.G., and Schwartz, M.W. Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats. Endocrinology. 144:2016-2024, 2003.

    Niswender, K.D., Morton, G.J., Stearns, W.H., Rhodes, C.J., Myers, M.G., Jr., and Schwartz, M.W. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature. 413:794-795, 2001.

 

Current Collaborations:

Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Denis Baskin, PhD
James E. Blevins, PhD
Jay Heinecke, MD
Rebecca Hull, PhD
Francis Kim, MD
Steven Kahn, MB, ChB
Dianne Lattemann, PhD
Renee LeBoeuf, PhD
Ellen Schur, MD
Michael Schwartz, MD
Jay Taborsky, PhD
Joshua Thaler, MD, PhD.
Brent Wisse, MD

Outside the Diabetes and Obesity Center of Excellence
Peter Havel, DVM, PhD
Chris Morrison, PhD
Martin G. Myers Jr., MD, PhD
Kevin Niswender, MD, PhD
Christopher Rhodes, PhD
Gary Schwartz, PhD
Streamson Chua Jr., PhD

Lab Members:

Thomas Meek, PhD
Hong Nguyen, BS
Kayoko Ogimoto, PhD
Miles Matsen, BS
Alex Cubelo, BS
JD Fischer, BS
Vincent Damian, BS
Jarrell Nelson, BS
Brendan Thatcher, BS
Loan Nguyen, BS