M W Schwartz

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. ncbi request reprint Diabetes, obesity, and the brain
    Michael W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98110, USA
    Science 307:375-9. 2005
  2. pmc Leptin and the brain: then and now
    Michael W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    J Clin Invest 123:2344-5. 2013
  3. pmc Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity
    Stephan J Guyenet
    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington School of Medicine, South Lake Union, 815 Mercer Street, N334, Box 358055, Seattle, Washington 98109, USA
    J Clin Endocrinol Metab 97:745-55. 2012
  4. ncbi request reprint Model for the regulation of energy balance and adiposity by the central nervous system
    M W Schwartz
    Department of Medicine, University of Washington, Harborview Medical Center and the VA Puget Sound Health Care System, Seattle 98108, USA
    Am J Clin Nutr 69:584-96. 1999
  5. ncbi request reprint Adiposity signaling and biological defense against weight gain: absence of protection or central hormone resistance?
    Michael W Schwartz
    Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington 98104, USA
    J Clin Endocrinol Metab 89:5889-97. 2004
  6. ncbi request reprint Central nervous system regulation of food intake
    Michael W Schwartz
    Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA
    Obesity (Silver Spring) 14:1S-8S. 2006
  7. ncbi request reprint Brain pathways controlling food intake and body weight
    M W Schwartz
    Department of Medicine, University of Washington and Harborview Medical Center, Seattle, Washington 98104, USA
    Exp Biol Med (Maywood) 226:978-81. 2001
  8. ncbi request reprint Biomedicine. Staying slim with insulin in mind
    M W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98105, USA
    Science 289:2066-7. 2000
  9. ncbi request reprint Evidence that elevated plasma corticosterone levels are the cause of reduced hypothalamic corticotrophin-releasing hormone gene expression in diabetes
    M W Schwartz
    Department of Medicine, University of Washington and Veterans Affairs Medical Center 151, Seattle 98108, USA
    Regul Pept 72:105-12. 1997
  10. ncbi request reprint Is the energy homeostasis system inherently biased toward weight gain?
    Michael W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 52:232-8. 2003

Research Grants

  1. NEUROENDOCRINE REGULATION OF ENERGY BALANCE
    Michael Schwartz; Fiscal Year: 2000
  2. NEUROENDOCRINE REGULATION OF ENERGY BALANCE
    Michael Schwartz; Fiscal Year: 2005
  3. HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETES
    Michael Schwartz; Fiscal Year: 2006
  4. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael Schwartz; Fiscal Year: 2007
  5. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael Schwartz; Fiscal Year: 2009
  6. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael W Schwartz; Fiscal Year: 2010
  7. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2010
  8. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2010
  9. Integration of Long- and Short-Term Control of Feeding
    Michael Schwartz; Fiscal Year: 2004
  10. REGULATION OF ENERGY BALANCE BY INSULIN
    Michael Schwartz; Fiscal Year: 1999

Detail Information

Publications101 found, 100 shown here

  1. ncbi request reprint Diabetes, obesity, and the brain
    Michael W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98110, USA
    Science 307:375-9. 2005
    ..Defects in this control system are implicated in the link between obesity and type 2 diabetes...
  2. pmc Leptin and the brain: then and now
    Michael W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    J Clin Invest 123:2344-5. 2013
    ..While substantial progress has been made in understanding brain mechanisms of leptin action, translating this knowledge into more effective treatment of obesity remains an elusive goal...
  3. pmc Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesity
    Stephan J Guyenet
    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington School of Medicine, South Lake Union, 815 Mercer Street, N334, Box 358055, Seattle, Washington 98109, USA
    J Clin Endocrinol Metab 97:745-55. 2012
    ..Because the growing obesity epidemic is linked to a substantial increase in daily energy intake, a key priority is to delineate how mechanisms governing food intake and body fat content are altered in an obesogenic environment...
  4. ncbi request reprint Model for the regulation of energy balance and adiposity by the central nervous system
    M W Schwartz
    Department of Medicine, University of Washington, Harborview Medical Center and the VA Puget Sound Health Care System, Seattle 98108, USA
    Am J Clin Nutr 69:584-96. 1999
    ..Our model of energy homeostasis proposes that long-term adiposity-related signals such as insulin and leptin influence the neuronal activity of central effector pathways that serve as controllers of energy balance...
  5. ncbi request reprint Adiposity signaling and biological defense against weight gain: absence of protection or central hormone resistance?
    Michael W Schwartz
    Department of Medicine, Harborview Medical Center, University of Washington, Seattle, Washington 98104, USA
    J Clin Endocrinol Metab 89:5889-97. 2004
    ..Here, we discuss these dichotomous possibilities within the context of current literature regarding energy homeostasis and suggest a strategy for distinguishing between them...
  6. ncbi request reprint Central nervous system regulation of food intake
    Michael W Schwartz
    Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA
    Obesity (Silver Spring) 14:1S-8S. 2006
  7. ncbi request reprint Brain pathways controlling food intake and body weight
    M W Schwartz
    Department of Medicine, University of Washington and Harborview Medical Center, Seattle, Washington 98104, USA
    Exp Biol Med (Maywood) 226:978-81. 2001
    ....
  8. ncbi request reprint Biomedicine. Staying slim with insulin in mind
    M W Schwartz
    Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA 98105, USA
    Science 289:2066-7. 2000
    ..flies in the face of the notion that insulin is involved solely in glucose storage, its conversion to fat, and weight gain...
  9. ncbi request reprint Evidence that elevated plasma corticosterone levels are the cause of reduced hypothalamic corticotrophin-releasing hormone gene expression in diabetes
    M W Schwartz
    Department of Medicine, University of Washington and Veterans Affairs Medical Center 151, Seattle 98108, USA
    Regul Pept 72:105-12. 1997
    ..These findings support a model in which hypothalamic factors additional to CRH activate the HPA axis in uncontrolled diabetes, and inhibit CRH gene expression indirectly by negative glucocorticoid feedback...
  10. ncbi request reprint Is the energy homeostasis system inherently biased toward weight gain?
    Michael W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 52:232-8. 2003
    ..Teleological, molecular, physiological, and clinical aspects of this hypothesis are presented, along with a discussion of currently available supporting evidence...
  11. ncbi request reprint Regulation of body adiposity and the problem of obesity
    M W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Arterioscler Thromb Vasc Biol 17:233-8. 1997
    ..Since the combination of a low-fat diet with an exercise program appears to reduce the level at which body weight is regulated without active caloric restriction, this approach may be appropriate for many obese individuals...
  12. ncbi request reprint Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms
    M W Schwartz
    Department of Medicine, University of Washington School of Medicine, Seattle, USA
    Diabetes Care 20:1476-81. 1997
    ....
  13. ncbi request reprint Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus
    M W Schwartz
    Department of Medicine, University of Washington, Pugent Sound VA Health Care System, Seattle 98108, USA
    Diabetes 46:2119-23. 1997
    ..These findings support the hypothesis that leptin signaling in the brain involves activation of the hypothalamic melanocortin system...
  14. ncbi request reprint Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter gene
    M W Schwartz
    Department of Medicine, University of Washington, and Puget Sound Veterans Affairs Health Care System, Seattle 98108, USA
    Endocrinology 139:2629-35. 1998
    ....
  15. ncbi request reprint Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice
    M W Schwartz
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 45:531-5. 1996
    ....
  16. ncbi request reprint Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting
    D G Baskin
    Department of Veterans Affairs Puget Sound Health Care System, Department of Medicine, University of Washington, Seattle 98108, USA
    Diabetes 47:538-43. 1998
    ....
  17. ncbi request reprint Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and co-localization with neuropeptide Y mRNA in the arcuate nucleus
    D G Baskin
    Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
    J Histochem Cytochem 47:353-62. 1999
    ..The present finding of Ob-Rb protein in neurons that express NPY mRNA supports the hypothesis that arcuate nucleus NPY neurons are direct targets of leptin and play an important role in regulation of food intake and body weight...
  18. pmc Reduced NO-cGMP signaling contributes to vascular inflammation and insulin resistance induced by high-fat feeding
    Norma O Rizzo
    Department of Medicine, University of Washington, Seattle, WA 98109, USA
    Arterioscler Thromb Vasc Biol 30:758-65. 2010
    ..We sought to determine whether reduced NO-cGMP signaling contributes to the deleterious effects of DIO on the vasculature and, if so, whether these effects can be blocked by increased vascular NO-cGMP signaling...
  19. ncbi request reprint Physiology. An integrative view of obesity
    Brent E Wisse
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, WA 98104, USA
    Science 318:928-9. 2007
  20. ncbi request reprint Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus
    D G Baskin
    Department of Medicine, University of Washington, Seattle, USA
    Diabetes 48:828-33. 1999
    ....
  21. ncbi request reprint Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting
    D S Weigle
    Department of Medicine, University of Washington, Harborview Medical Center, Seattle 98104, USA
    Diabetes 47:298-302. 1998
    ..This seemingly paradoxical induction of UCP3 may be linked to the use of free fatty acid as a fuel rather than an increased need of the organism to dissipate energy...
  22. pmc Leptin action in the forebrain regulates the hindbrain response to satiety signals
    Gregory J Morton
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington 98104, USA
    J Clin Invest 115:703-10. 2005
    ..These findings demonstrate that forebrain signaling by leptin, a long-term regulator of body adiposity, limits food intake on a meal-to-meal basis by regulating the hindbrain response to short-acting satiety signals...
  23. ncbi request reprint SOCS-3 expression in leptin-sensitive neurons of the hypothalamus of fed and fasted rats
    D G Baskin
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, 98185, Seattle, WA, USA
    Regul Pept 92:9-15. 2000
    ....
  24. ncbi request reprint Intraventricular leptin reduces food intake and body weight of lean rats but not obese Zucker rats
    R J Seeley
    Department of Psychology, University of Washington, Seattle 98195-1525, USA
    Horm Metab Res 28:664-8. 1996
    ..Furthermore, insensitivity to these central effects of leptin may be an important determinant of obesity...
  25. pmc Atypical protein kinase C activity in the hypothalamus is required for lipopolysaccharide-mediated sickness responses
    Joshua P Thaler
    Division of Metabolism, University of Washington, Seattle, Washington 98109, USA
    Endocrinology 150:5362-72. 2009
    ..We conclude that although hypothalamic aPKC signaling is not required for food intake inhibition by insulin or leptin, it plays a key role in inflammatory anorexia and fever induced by LPS...
  26. ncbi request reprint Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling
    Christopher D Morrison
    University of Washington, Harborview Medical Center, Box 359757, 325 Ninth Ave, Seattle, WA 98108, USA
    Am J Physiol Endocrinol Metab 289:E1051-7. 2005
    ..In addition, these data suggest that leptin activation of STAT3 is insufficient to inhibit expression of Npy or Agrp in the absence of PI3K signaling...
  27. ncbi request reprint Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons
    Gregory J Morton
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, WA 98104, USA
    Cell Metab 2:411-20. 2005
    ..These findings suggest that hypothalamic leptin signaling is an important determinant of glucose metabolism and that the underlying neuronal mechanism involves PI3K...
  28. ncbi request reprint Leptin sensitive neurons in the hypothalamus
    D G Baskin
    VA Puget Sound Health Care System, Department of Medicine, University of Washington School of Medicine, Seattle 98108 1597, USA
    Horm Metab Res 31:345-50. 1999
    ..These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling, and that the arcuate nucleus is an important target of leptin action in the brain...
  29. ncbi request reprint Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weight
    D G Baskin
    Division of Endocrinology Metabolism, VA Puget Sound Health Care System Medical Center, Seattle, WA 98108, USA
    Brain Res 848:114-23. 1999
    ..The recent findings that insulin alters the expression and function of neural transporters for dopamine and norepinephrine indicate that adiposity signals may influence food intake by acting on non-peptide neurotransmitter systems...
  30. pmc Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese rats
    David A Sarruf
    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, Washington, USA
    Diabetes 59:1817-24. 2010
    ..The current studies investigate whether central FGF21 treatment recapitulates these effects...
  31. doi request reprint Hypothalamic inflammation and energy homeostasis: resolving the paradox
    Joshua P Thaler
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98108, USA
    Front Neuroendocrinol 31:79-84. 2010
    ..Rigorously evaluating the progression of the inflammatory signaling cascade within specific hypothalamic cell types is a key next step towards resolving the paradox surrounding the effect of inflammatory signaling on energy homeostasis...
  32. pmc Leptin deficiency causes insulin resistance induced by uncontrolled diabetes
    Jonathan P German
    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, Washington, USA
    Diabetes 59:1626-34. 2010
    ..This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM...
  33. ncbi request reprint Attenuation of diabetic hyperphagia in neuropeptide Y--deficient mice
    Dana K Sindelar
    Department of Medicine, University of Washington, Seattle, Washington, USA
    Diabetes 51:778-83. 2002
    ....
  34. ncbi request reprint Behavioral, endocrine, and hypothalamic responses to involuntary overfeeding
    R J Seeley
    Department of Psychology, University of Washington, Seattle 98195 1525, USA
    Am J Physiol 271:R819-23. 1996
    ..Furthermore, the hypothalamic NPY response to food restriction is not tied to low food intake per se, but rather to negative energy balance...
  35. ncbi request reprint The NPY/AgRP neuron and energy homeostasis
    G J Morton
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington 98104, USA
    Int J Obes Relat Metab Disord 25:S56-62. 2001
    ..Data are reviewed which illustrate the role of these neurons in adaptive and maladaptive states characterized by hyperphagia and weight gain...
  36. pmc Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feeding
    Shinsuke Oh-I
    UW Medicine at South Lake Union, Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, 815 Mercer St, Seattle, WA 98109, USA
    Am J Physiol Endocrinol Metab 299:E47-53. 2010
    ..These observations add to growing evidence linking hypothalamic inflammation to obesity pathogenesis...
  37. ncbi request reprint Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities
    Kevin D Niswender
    Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine and Harborview Medical Center, Seattle, WA 98104, USA
    Front Neuroendocrinol 24:1-10. 2003
    ..Identification of the key early molecular events mediating the action of both insulin and leptin in hypothalamic neurons promises new insight into the regulation of these neurons in health and disease...
  38. pmc A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain
    Denis G Baskin
    Office of Research and Development Medical Research Service, Veterans Affairs Puget Sound Health Care System, Department of Veterans Affairs Medical Center, Seattle, Washington 98108, USA
    Endocrinology 151:4207-13. 2010
    ....
  39. pmc Mice lacking hepatic lipase are lean and protected against diet-induced obesity and hepatic steatosis
    Harvey K Chiu
    Department of Pediatrics, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA
    Endocrinology 151:993-1001. 2010
    ..Our results demonstrate that in mice, HL deficiency protects against diet-induced obesity and its hepatic sequelae. Inhibition of HL-activity may therefore have value in the prevention and/or treatment of obesity...
  40. ncbi request reprint Reversal of cancer anorexia by blockade of central melanocortin receptors in rats
    B E Wisse
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington 98108, USA
    Endocrinology 142:3292-301. 2001
    ..This suggests that new targets for the treatment of cancer anorexia may be found in the melanocortin pathways...
  41. pmc Activation of NF-kappaB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation
    Ezekiel Maloney
    Department of Medicine, University of Washington, Seattle, WA 98109, USA
    Arterioscler Thromb Vasc Biol 29:1370-5. 2009
    ..We investigated whether NADPH oxidase-dependent production of superoxide contributes to activation of NF-kappaB in endothelial cells by the saturated free fatty acid palmitate...
  42. pmc Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis
    David A Sarruf
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98195, USA
    Endocrinology 150:707-12. 2009
    ....
  43. ncbi request reprint Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) rats
    Gregory J Morton
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington 98104, USA
    Endocrinology 144:2016-24. 2003
    ..Adenoviral gene therapy is thus a viable strategy with which to study the physiological importance of specific molecules acting in discrete brain areas...
  44. ncbi request reprint How the brain regulates food intake and body weight: the role of leptin
    D G Baskin
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, USA
    J Pediatr Endocrinol Metab 14:1417-29. 2001
    ..This mechanism explains how leptin deficiency or defects in the brain's processing of leptin signaling can result in a sustained increase in food intake and obesity...
  45. pmc Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids
    Sun Ju Choi
    Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine and Diabetes, University of Washington, Seattle, WA 98109 4714, USA
    Am J Physiol Endocrinol Metab 298:E1122-30. 2010
    ..Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells...
  46. doi request reprint Does hypothalamic inflammation cause obesity?
    Brent E Wisse
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98195, USA
    Cell Metab 10:241-2. 2009
    ..2009) add to growing evidence that this response occurs in the hypothalamus, as well as in peripheral tissues, which helps to explain how high-fat feeding induces a gradual increase in defended body weight...
  47. ncbi request reprint Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans
    Daniel Porte
    Division of Metabolism, Diabetes, and Endocrinology, University of California San Diego, USA
    Diabetes 54:1264-76. 2005
    ..These considerations implicate insulin action in the brain, an organ previously considered to be insulin independent, as a key determinant of both glucose and energy homeostasis...
  48. ncbi request reprint Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis
    Aaron W Pardini
    Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, USA
    Brain Res 1112:169-78. 2006
    ..An improved understanding of mechanisms underlying normal and abnormal energy homeostasis may be gained by analysis of the role played by signaling through IRS-2 in these brain areas...
  49. ncbi request reprint Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia
    Kevin D Niswender
    Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine and Harborview Medical Center, Seattle 98104, USA
    Diabetes 52:227-31. 2003
    ....
  50. ncbi request reprint Neuronal pathways regulating food intake and body adiposity
    M W Schwartz
    University of Washington and Harborview Medical Center Division of Endocrinology, 325 9th Avenue Seattle, WA 98104, USA
    Ann Endocrinol (Paris) 63:117-20. 2002
  51. ncbi request reprint Central nervous system control of food intake and body weight
    G J Morton
    Department of Medicine, Harborview Medical Center and University of Washington, Seattle, Washington 98104, USA
    Nature 443:289-95. 2006
    ..This new information provides a biological context within which to consider the global obesity epidemic and identifies numerous potential avenues for therapeutic intervention and future research...
  52. pmc Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice
    Richard W Gelling
    Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    Endocrinology 149:6053-64. 2008
    ..These findings collectively identify a novel and potentially important role for TACE in energy homeostasis...
  53. pmc Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up
    Joshua P Thaler
    Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington 98109, USA
    Endocrinology 151:4109-15. 2010
    ..This article highlights molecular and cellular mechanisms by which hypothalamic inflammation predisposes to diet-induced obesity...
  54. pmc Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A
    Linda C Enns
    Department of Comparative Medicine, University of Washington, Seattle, WA, 98915, USA
    J Gerontol A Biol Sci Med Sci 64:1221-31. 2009
    ..These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance...
  55. doi request reprint Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8
    James E Blevins
    VA Puget Sound Health Care System, Mail stop S 151, 1660 South Columbian Way, Seattle, WA 98108, USA
    Am J Physiol Regul Integr Comp Physiol 296:R476-84. 2009
    ....
  56. pmc Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in mice
    Gregory J Morton
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, USA
    Am J Physiol Endocrinol Metab 300:E392-401. 2011
    ..Thus, plasma leptin is a physiological regulator of spontaneous physical activity, but the nature of leptin's effect on activity is dependent on food availability...
  57. ncbi request reprint Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation
    Diana L Williams
    University of Washington, Harborview Medical Center, 325 9th Ave, Box 359675, Seattle, WA 98104, USA
    Diabetes 55:3387-93. 2006
    ....
  58. pmc Central interleukin-1 (IL1) signaling is required for pharmacological, but not physiological, effects of leptin on energy balance
    Brent E Wisse
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98108, USA
    Brain Res 1144:101-6. 2007
    ....
  59. ncbi request reprint Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity
    Francis Kim
    Department of Medicine, University of Washington, Seattle, WA 98104, USA
    Circ Res 100:1589-96. 2007
    ....
  60. pmc Identification of body fat mass as a major determinant of metabolic rate in mice
    Karl J Kaiyala
    Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, USA
    Diabetes 59:1657-66. 2010
    ....
  61. ncbi request reprint Evidence that lipopolysaccharide-induced anorexia depends upon central, rather than peripheral, inflammatory signals
    Brent E Wisse
    Division of Metabolism, Harborview Medical Center, Seattle, WA 98104 2499, USA
    Endocrinology 148:5230-7. 2007
    ....
  62. pmc Immunocytochemistry and laser capture microdissection for real-time quantitative PCR identify hindbrain neurons activated by interaction between leptin and cholecystokinin
    Diana L Williams
    Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA
    J Histochem Cytochem 56:285-93. 2008
    ..These histochemical findings identify hindbrain catecholamine cells as potential mediators of the interaction between leptin and CCK...
  63. pmc Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance
    Francis Kim
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98104, USA
    Arterioscler Thromb Vasc Biol 28:1982-8. 2008
    ....
  64. pmc Receptors for tumor necrosis factor-alpha play a protective role against obesity and alter adipose tissue macrophage status
    Nathalie Pamir
    Department of Medicine, Division of Metabolism, Endocrinology, andNutrition and the Diabetes and Obesity Center of Excellence, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98109 8050, USA
    Endocrinology 150:4124-34. 2009
    ..Despite these effects, TNFRs are not required for obesity-induced insulin resistance...
  65. pmc Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve
    Jonathan German
    Department of Medicine, University of Washington at South Lake Union, 815 Mercer Street, Box 358055, Seattle, Washington 98195
    Endocrinology 150:4502-11. 2009
    ..We conclude that hypothalamic leptin action increases peripheral insulin sensitivity primarily via effects on the liver and that the mechanism underlying this effect is dependent on the hepatic branch of the vagus nerve...
  66. ncbi request reprint Peptide signals regulating food intake and energy homeostasis
    James E Blevins
    Department of Medicine, University of Washington School of Medicine, Seattle 98108, USA
    Can J Physiol Pharmacol 80:396-406. 2002
    ....
  67. ncbi request reprint Physiological regulation of hypothalamic IL-1beta gene expression by leptin and glucocorticoids: implications for energy homeostasis
    Brent E Wisse
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359757, Seattle, WA 98104 2499, USA
    Am J Physiol Endocrinol Metab 287:E1107-13. 2004
    ..05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1beta is subject to opposing physiological regulation by corticosterone and leptin...
  68. ncbi request reprint Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size
    James E Blevins
    VA Puget Sound Health Care System, Research Service 151 1660 S Columbian Wy, Seattle, WA 98108, USA
    Am J Physiol Regul Integr Comp Physiol 287:R87-96. 2004
    ....
  69. ncbi request reprint Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin
    James E Blevins
    Division of Endocrinology Metabolism, VA Puget Sound Health Care System, Seattle, WA 98108, USA
    Brain Res 993:30-41. 2003
    ..These findings support the hypothesis that oxytocin exerts a tonic stimulatory effect on the response of key neurons within the NTS to CCK and further reduce meal size...
  70. ncbi request reprint Activation of IKKbeta by glucose is necessary and sufficient to impair insulin signaling and nitric oxide production in endothelial cells
    Francis Kim
    Department of Medicine, Harborview Medical Center, University of Washington, Box 359748, Seattle, WA 98104, USA
    J Mol Cell Cardiol 39:327-34. 2005
    ..These data demonstrate that activation of IKKbeta plays a critical and novel role to mediate the deleterious effects of high glucose on endothelial cell function...
  71. ncbi request reprint Melanocortin signaling and anorexia in chronic disease states
    Brent E Wisse
    Division of Metabolism, Endocrinology and Nutrition, Harborview Medical Center, University of Washington, Seattle, Washington 98104, USA
    Ann N Y Acad Sci 994:275-81. 2003
    ..The data presented in this paper summarize findings that implicate neuronal melanocortin signaling in inflammatory anorexia...
  72. ncbi request reprint Role of hypothalamic interleukin-1beta (IL-1beta) in regulation of energy homeostasis by melanocortins
    Brent E Wisse
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98108, USA
    Peptides 27:265-73. 2006
    ..These data suggest a potential role for central melanocortins in mediating the decrease of ambulation characteristic of the 'sickness' response...
  73. ncbi request reprint Genetics and pathophysiology of human obesity
    David E Cummings
    Department of Medicine, VA Puget Sound Health Care System and Harborview Medical Center, University of Washington, Seattle, Washington 98195, USA
    Annu Rev Med 54:453-71. 2003
    ..This article highlights some of these recent findings and their implications for the future of obesity treatment...
  74. ncbi request reprint Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin
    Kevin D Niswender
    Division of Metabolism, Endocrinology and Nutrition, Seattle, Washington, USA
    J Histochem Cytochem 51:275-83. 2003
    ..We conclude that immunocytochemical PIP3 staining can detect changes in PI3K activation induced by insulin and leptin in cell culture and intact liver...
  75. pmc Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus
    E A Schur
    Division of General Internal Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA
    Int J Obes (Lond) 33:653-61. 2009
    ..To develop a non-invasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss...
  76. ncbi request reprint Neuropeptide Y is required for hyperphagic feeding in response to neuroglucopenia
    Dana K Sindelar
    Department of Medicine, Harborview Medical Centr, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA
    Endocrinology 145:3363-8. 2004
    ..We conclude that NPY signaling is required for hyperphagic feeding, but not neuroendocrine responses to moderate hypoglycemia...
  77. ncbi request reprint Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feeding
    Richard W Gelling
    Department of Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359657, Seattle, Washington 98104, USA
    Endocrinology 145:4575-82. 2004
    ..Although plasma ghrelin levels fall in response to hyperphagic feeding, these findings support the hypothesis that increased ghrelin signaling contributes to the pathogenesis of diabetic hyperphagia...
  78. ncbi request reprint Increased hypothalamic melanin concentrating hormone gene expression during energy restriction involves a melanocortin-independent, estrogen-sensitive mechanism
    Gregory J Morton
    Department of Medicine, Harborview Medical Center, University of Washington, 325 Ninth Avenue, Box 359757, Seattle, WA 98104, USA
    Peptides 25:667-74. 2004
    ..These findings suggest that while both energy restriction and reduced melanocortin signaling stimulate hypothalamic Mch gene expression, they do so via distinct mechanisms...
  79. pmc Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respiration
    I R Sweet
    Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington at South Lake Union, Seattle, Washington 98195 8055, USA
    Diabetologia 52:921-31. 2009
    ..Since endothelial cells decrease their oxygen consumption rate (OCR) in response to glucose, we hypothesised that increased mitochondrial function would not mediate these cells' response to excess substrate...
  80. ncbi request reprint Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults
    Mark A Fishel
    Department of Neurology, University of Washington, Seattle, WA 98108, USA
    Arch Neurol 62:1539-44. 2005
    ..Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network...
  81. ncbi request reprint Attenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide Y
    Dana K Sindelar
    Department of Medicine, University of Washington, Harborview Hospital, Division of Endocrinology, Box 359757, 325 9th Avenue, Seattle, WA 98104, USA
    Peptides 26:2597-602. 2005
    ....
  82. ncbi request reprint Elevated plasma ghrelin levels in Prader Willi syndrome
    David E Cummings
    Department of Medicine, VA Puget Sound Health Care System and Harborview Medical Center University of Washington, Seattle, Washington, USA
    Nat Med 8:643-4. 2002
  83. ncbi request reprint Leptin and insulin action in the central nervous system
    Daniel Porte
    Division of Metabolism, Diabetes, Endocrinology, University of California San Diego, USA
    Nutr Rev 60:S20-9; discussion S68-84, 85-7. 2002
    ..Recently described contributions of this system to obesity are described and potential therapeutic implications are discussed...
  84. ncbi request reprint Insulin increases CSF Abeta42 levels in normal older adults
    G S Watson
    Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle 98108, USA
    Neurology 60:1899-903. 2003
    ..In vitro studies show that insulin enhances the release of beta-amyloid protein (Abeta) or inhibits its degradation, either of which might increase amyloid burden...
  85. ncbi request reprint Determinants of insulin availability in parenteral nutrition solutions
    Matthew A Christianson
    Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, Washington 98108, USA
    JPEN J Parenter Enteral Nutr 30:6-9. 2006
    ..The purpose of this study was to evaluate insulin recovery from a standard PN solution used at our medical center...
  86. ncbi request reprint Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration
    Patrick Weydt
    Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA
    Cell Metab 4:349-62. 2006
    ..Finally, HD striatal neurons expressing exogenous PGC-1alpha were resistant to 3-nitropropionic acid treatment. Altered PGC-1alpha function may thus link transcription dysregulation and mitochondrial dysfunction in HD...
  87. ncbi request reprint Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasis
    Kevin D Niswender
    Diabetes, Endocrinology and Metabolism, 722 Preston Research Building, Vanderbilt University Medical Center, 2220 Pierce Avenue, Nashville, TN 37232 6303, USA
    Trends Endocrinol Metab 15:362-9. 2004
    ..These pathways are thus an attractive target for pharmacological intervention in the treatment of obesity...
  88. pmc Effects of hypothalamic neurodegeneration on energy balance
    Allison Wanting Xu
    Department of Genetics, Stanford University School of Medicine, Stanford, California, USA
    PLoS Biol 3:e415. 2005
    ..These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging...
  89. ncbi request reprint STAT3 signalling is required for leptin regulation of energy balance but not reproduction
    Sarah H Bates
    Research Division, Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA
    Nature 421:856-9. 2003
    ..LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis...
  90. ncbi request reprint Adrenalectomy alters the sensitivity of the central nervous system melanocortin system
    Deborah L Drazen
    Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237, USA
    Diabetes 52:2928-34. 2003
    ..We conclude that the potent weight-reducing effects of ADX likely involve heightened responsiveness to melanocortin receptor stimulation...
  91. ncbi request reprint Signal transducer and activator of transcription (stat) binding sites but not stat3 are required for fasting-induced transcription of agouti-related protein messenger ribonucleic acid
    Christopher B Kaelin
    Department of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
    Mol Endocrinol 20:2591-602. 2006
    ....
  92. ncbi request reprint Rats lighten up with MCH antagonist
    Michael W Schwartz
    Nat Med 8:779-81. 2002
  93. ncbi request reprint The melanocortin system as a central integrator of direct and indirect controls of food intake
    Diana L Williams
    Am J Physiol Regul Integr Comp Physiol 289:R2-3. 2005
  94. ncbi request reprint Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance
    James Trevaskis
    Metabolic Research Unit, School of Exercise and Nutrition Sciences, Deakin University, Geelong 3217, Victoria, Australia
    Endocrinology 146:3757-64. 2005
    ..Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis...
  95. pmc PI3K integrates the action of insulin and leptin on hypothalamic neurons
    Allison Wanting Xu
    Department of Genetics, Stanford University School of Medicine, Stanford, California, USA
    J Clin Invest 115:951-8. 2005
    ..These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons...
  96. ncbi request reprint Genetic approaches to studying energy balance: perception and integration
    Gregory S Barsh
    1 Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305 5208, USA
    Nat Rev Genet 3:589-600. 2002
  97. ncbi request reprint Obesity: keeping hunger at bay
    Michael W Schwartz
    Nature 418:595-7. 2002
  98. ncbi request reprint Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake
    Harvey J Grill
    Graduate Group of Psychology, Dept of Psychology, University of Pennsylvania, 3815 Walnut Street, Philadelphia, PA 19104, USA
    Endocrinology 143:239-46. 2002
    ..The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis...
  99. ncbi request reprint Out of synch: Clock mutation causes obesity in mice
    Diana L Williams
    Department of Medicine, Harborview Medical Center, and University of Washington, Seattle, Washington 98104, USA
    Cell Metab 1:355-6. 2005
    ..New evidence that Clock mutant mice are hyperphagic and obese suggests a previously unrecognized link between molecular controls of circadian rhythm and energy homeostasis...
  100. ncbi request reprint The skinny on neurotrophins
    Brent E Wisse
    Nat Neurosci 6:655-6. 2003
  101. ncbi request reprint Insulin and the blood-brain barrier
    Stephen C Woods
    Department of Psychiatry, Box 670559, University of Cincinnati, Cincinnati, OH 45267, USA
    Curr Pharm Des 9:795-800. 2003
    ..Within the brain insulin acts on specific receptors to influence a number of behaviors, and especially caloric homeostasis and cognition...

Research Grants36

  1. NEUROENDOCRINE REGULATION OF ENERGY BALANCE
    Michael Schwartz; Fiscal Year: 2000
    ..Substantial progression the development of effective therapeutic strategies for disorders of body weight across the spectrum ranging from obesity to wasting illness can be anticipated from this new knowledge. ..
  2. NEUROENDOCRINE REGULATION OF ENERGY BALANCE
    Michael Schwartz; Fiscal Year: 2005
    ..This information will help to clarify how energy homeostasis occurs and has the potential to identify new targets for drug development in obesity treatment. ..
  3. HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETES
    Michael Schwartz; Fiscal Year: 2006
    ..abstract_text> ..
  4. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael Schwartz; Fiscal Year: 2007
    ....
  5. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael Schwartz; Fiscal Year: 2009
    ....
  6. Neuroendocrine Control of Energy Balance and Insulin Sensitivity
    Michael W Schwartz; Fiscal Year: 2010
    ....
  7. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2010
    ..By improving our understanding of how mechanisms driving obesity and diabetes are linked to one another within the brain, our ultimate goal is to find new strategies for their prevention and treatment. ..
  8. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2010
    ..abstract_text> ..
  9. Integration of Long- and Short-Term Control of Feeding
    Michael Schwartz; Fiscal Year: 2004
    ....
  10. REGULATION OF ENERGY BALANCE BY INSULIN
    Michael Schwartz; Fiscal Year: 1999
    ..Ultimately, we wish to understand the insulin/glucocorticoid/NPY body weight regulatory system and determine how this system might be modulated to influence the development of obesity. ..
  11. HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETES
    Michael Schwartz; Fiscal Year: 2002
    ..abstract_text> ..
  12. Conference on Obesity
    Michael Schwartz; Fiscal Year: 2003
    ..Progress towards improved therapeutic options for obesity and their implications for public health and public policy will be emphasized. ..
  13. INTEGRATION OF LONG - AND SHORT-TERM CONTROL OF FEEDING
    Michael Schwartz; Fiscal Year: 2003
    ..By improving our understanding of the integration of long and short-term regulators of energy intake, these studies will help to identify sites for therapeutic intervention in the treatment of obesity and other weight disorders. ..
  14. Hypothalamic Inflammation and Energy Homeostasis
    Michael W Schwartz; Fiscal Year: 2010
    ....