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Genomes and Genes | M W SchwartzSummaryAffiliation: University of Washington Country: USA Publications
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Diabetes, obesity, and the brainMichael 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...
Clinical review: Regulation of food intake, energy balance, and body fat mass: implications for the pathogenesis and treatment of obesityStephan 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...- Model for the regulation of energy balance and adiposity by the central nervous systemM 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... - 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... - Brain pathways controlling food intake and body weightM W Schwartz
Department of Medicine, University of Washington and Harborview Medical Center, Seattle, Washington 98104, USA
Exp Biol Med (Maywood) 226:978-81. 2001.... - Central nervous system regulation of food intakeMichael W Schwartz
Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA 98104, USA
Obesity (Silver Spring) 14:1S-8S. 2006 - Biomedicine. Staying slim with insulin in mindM 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... - 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... - Evidence that elevated plasma corticosterone levels are the cause of reduced hypothalamic corticotrophin-releasing hormone gene expression in diabetesM 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... - Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleusM 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... - Regulation of body adiposity and the problem of obesityM 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... - Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanismsM W Schwartz
Department of Medicine, University of Washington School of Medicine, Seattle, USA
Diabetes Care 20:1476-81. 1997.... - Effect of fasting and leptin deficiency on hypothalamic neuropeptide Y gene transcription in vivo revealed by expression of a lacZ reporter geneM W Schwartz
Department of Medicine, University of Washington, and Puget Sound Veterans Affairs Health Care System, Seattle 98108, USA
Endocrinology 139:2629-35. 1998.... - Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob miceM W Schwartz
Department of Medicine, University of Washington, Seattle, USA
Diabetes 45:531-5. 1996.... - Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fastingD 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.... - 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 nucleusD 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... - Reduced NO-cGMP signaling contributes to vascular inflammation and insulin resistance induced by high-fat feedingNorma 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... - Physiology. An integrative view of obesityBrent E Wisse
Department of Medicine, Harborview Medical Center and University of Washington, Seattle, WA 98104, USA
Science 318:928-9. 2007 - Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamusD G Baskin
Department of Medicine, University of Washington, Seattle, USA
Diabetes 48:828-33. 1999.... - Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fastingD 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... - Leptin action in the forebrain regulates the hindbrain response to satiety signalsGregory 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... - Intraventricular leptin reduces food intake and body weight of lean rats but not obese Zucker ratsR 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... - SOCS-3 expression in leptin-sensitive neurons of the hypothalamus of fed and fasted ratsD 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.... - Atypical protein kinase C activity in the hypothalamus is required for lipopolysaccharide-mediated sickness responsesJoshua 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... - Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neuronsGregory 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... - Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signalingChristopher 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... - Leptin sensitive neurons in the hypothalamusD 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... - Insulin and leptin: dual adiposity signals to the brain for the regulation of food intake and body weightD 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... - Leptin deficiency causes insulin resistance induced by uncontrolled diabetesJonathan 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... 
Hypothalamic inflammation and energy homeostasis: resolving the paradoxJoshua 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...- Attenuation of diabetic hyperphagia in neuropeptide Y--deficient miceDana K Sindelar
Department of Medicine, University of Washington, Seattle, Washington, USA
Diabetes 51:778-83. 2002.... - Fibroblast growth factor 21 action in the brain increases energy expenditure and insulin sensitivity in obese ratsDavid 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... - Behavioral, endocrine, and hypothalamic responses to involuntary overfeedingR 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... - The NPY/AgRP neuron and energy homeostasisG 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... - A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrainDenis 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.... - Central administration of interleukin-4 exacerbates hypothalamic inflammation and weight gain during high-fat feedingShinsuke 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... - Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilitiesKevin 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... - Mice lacking hepatic lipase are lean and protected against diet-induced obesity and hepatic steatosisHarvey 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... - Reversal of cancer anorexia by blockade of central melanocortin receptors in ratsB 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... - Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasisDavid A Sarruf
Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98195, USA
Endocrinology 150:707-12. 2009.... - Activation of NF-kappaB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activationEzekiel 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... - Arcuate nucleus-specific leptin receptor gene therapy attenuates the obesity phenotype of Koletsky (fa(k)/fa(k)) ratsGregory 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... - How the brain regulates food intake and body weight: the role of leptinD 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... - 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... - Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasisAaron 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... - Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acidsSun 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... - Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexiaKevin 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.... - Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humansDaniel 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... - Neuronal pathways regulating food intake and body adiposityM 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 - Central nervous system control of food intake and body weightG 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... - Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats upJoshua 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... - Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase ALinda 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... - Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in miceRichard 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... - Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerveJonathan 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... - Receptors for tumor necrosis factor-alpha play a protective role against obesity and alter adipose tissue macrophage statusNathalie 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... - Forebrain melanocortin signaling enhances the hindbrain satiety response to CCK-8James 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.... - Identification of body fat mass as a major determinant of metabolic rate in miceKarl J Kaiyala
Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, USA
Diabetes 59:1657-66. 2010.... - Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulationDiana L Williams
University of Washington, Harborview Medical Center, 325 9th Ave, Box 359675, Seattle, WA 98104, USA
Diabetes 55:3387-93. 2006.... - Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesityFrancis Kim
Department of Medicine, University of Washington, Seattle, WA 98104, USA
Circ Res 100:1589-96. 2007.... - Evidence that lipopolysaccharide-induced anorexia depends upon central, rather than peripheral, inflammatory signalsBrent E Wisse
Division of Metabolism, Harborview Medical Center, Seattle, WA 98104 2499, USA
Endocrinology 148:5230-7. 2007.... - Immunocytochemistry and laser capture microdissection for real-time quantitative PCR identify hindbrain neurons activated by interaction between leptin and cholecystokininDiana 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... - Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistanceFrancis 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.... - Identification of a physiological role for leptin in the regulation of ambulatory activity and wheel running in miceGregory 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... - Central interleukin-1 (IL1) signaling is required for pharmacological, but not physiological, effects of leptin on energy balanceBrent 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.... - Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal sizeJames 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.... - Activation of IKKbeta by glucose is necessary and sufficient to impair insulin signaling and nitric oxide production in endothelial cellsFrancis 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... - Oxytocin innervation of caudal brainstem nuclei activated by cholecystokininJames 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... - Melanocortin signaling and anorexia in chronic disease statesBrent 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... - Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptinKevin 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... - Genetics and pathophysiology of human obesityDavid 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... - Role of hypothalamic interleukin-1beta (IL-1beta) in regulation of energy homeostasis by melanocortinsBrent 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... - Peptide signals regulating food intake and energy homeostasisJames E Blevins
Department of Medicine, University of Washington School of Medicine, Seattle 98108, USA
Can J Physiol Pharmacol 80:396-406. 2002.... - Physiological regulation of hypothalamic IL-1beta gene expression by leptin and glucocorticoids: implications for energy homeostasisBrent 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... - Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulusE 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... - Increased hypothalamic melanin concentrating hormone gene expression during energy restriction involves a melanocortin-independent, estrogen-sensitive mechanismGregory 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... - Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feedingRichard 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... - Neuropeptide Y is required for hyperphagic feeding in response to neuroglucopeniaDana 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... - Endothelial inflammation induced by excess glucose is associated with cytosolic glucose 6-phosphate but not increased mitochondrial respirationI 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... - Elevated plasma ghrelin levels in Prader Willi syndromeDavid 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 - Leptin and insulin action in the central nervous systemDaniel 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... - Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adultsMark A Fishel
Department of Neurology, University of Washington, Seattle, WA 98108, USA
Arch Neurol 62:1539-44. 2005..05). CONCLUSION: Moderate hyperinsulinemia can elevate inflammatory markers and Abeta42 in the periphery and the brain, thereby potentially increasing the risk of Alzheimer disease... - Attenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide YDana 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.... - Insulin increases CSF Abeta42 levels in normal older adultsG 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... - Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegenerationPatrick 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... - Determinants of insulin availability in parenteral nutrition solutionsMatthew 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... 
Effects of hypothalamic neurodegeneration on energy balanceAllison 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...- PI3K integrates the action of insulin and leptin on hypothalamic neuronsAllison 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... - Rats lighten up with MCH antagonistMichael W Schwartz
Nat Med 8:779-81. 2002 - Genetic approaches to studying energy balance: perception and integrationGregory S Barsh
1] Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA
Nat Rev Genet 3:589-600. 2002 - Obesity: keeping hunger at bayMichael W Schwartz
Nature 418:595-7. 2002 - Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intakeHarvey 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... - Signal transducer and activator of transcription (stat) binding sites but not stat3 are required for fasting-induced transcription of agouti-related protein messenger ribonucleic acidChristopher B Kaelin
Department of Genetics and Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Mol Endocrinol 20:2591-602. 2006.... - Insulin and its evolving partnership with leptin in the hypothalamic control of energy homeostasisKevin 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... - STAT3 signalling is required for leptin regulation of energy balance but not reproductionSarah 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... - The melanocortin system as a central integrator of direct and indirect controls of food intakeDiana L Williams
Am J Physiol Regul Integr Comp Physiol 289:R2-3. 2005 - Adrenalectomy alters the sensitivity of the central nervous system melanocortin systemDeborah 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... - Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balanceJames 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... - Insulin and the blood-brain barrierStephen 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... - The skinny on neurotrophinsBrent E Wisse
Nat Neurosci 6:655-6. 2003 - Out of synch: Clock mutation causes obesity in miceDiana 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...
Research Grants
- NEUROENDOCRINE REGULATION OF ENERGY BALANCEMichael 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. ..
- NEUROENDOCRINE REGULATION OF ENERGY BALANCEMichael 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. ..
- HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETESMichael Schwartz; Fiscal Year: 2006..abstract_text> ..
- Neuroendocrine Control of Energy Balance and Insulin SensitivityMichael Schwartz; Fiscal Year: 2007....
- Neuroendocrine Control of Energy Balance and Insulin SensitivityMichael Schwartz; Fiscal Year: 2009....
- Neuroendocrine Control of Energy Balance and Insulin SensitivityMichael W Schwartz; Fiscal Year: 2010....
- Mechanisms of Diabetic Hyperphagia and Insulin ResistanceMichael 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. ..
- Mechanisms of Diabetic Hyperphagia and Insulin ResistanceMichael W Schwartz; Fiscal Year: 2010..abstract_text> ..
- Integration of Long- and Short-Term Control of FeedingMichael Schwartz; Fiscal Year: 2004....
- REGULATION OF ENERGY BALANCE BY INSULINMichael 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. ..
- HYPOTHALAMIC PEPTIDES, FOOD INTAKE, AND DIABETESMichael Schwartz; Fiscal Year: 2002..abstract_text> ..
- Conference on ObesityMichael Schwartz; Fiscal Year: 2003..Progress towards improved therapeutic options for obesity and their implications for public health and public policy will be emphasized. ..
- INTEGRATION OF LONG - AND SHORT-TERM CONTROL OF FEEDINGMichael 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. ..
- Hypothalamic Inflammation and Energy HomeostasisMichael W Schwartz; Fiscal Year: 2010....