PERIPHERAL AND CENTRAL INTERACTIONS IN ENERGY BALANCE

Summary

Principal Investigator: Barbara B Kahn
Abstract: Peripheral and Central Interactions in Energy Balance (Barbara B. Kahn, MD, Principal Investigator, Beth Israel Deaconess Medical Center). Obesity and related disorders such as Type 2 diabetes mellitus are major healthcare issues in the United States, and decreasing their incidence in adults and children would have profound social and economic ramifications. For this to occur, an increased understanding of the mechanisms controlling food intake and body weight is essential. There has been tremendous recent progress in elucidating critical metabolic signals and the oathways in the brain and in peripheral tissues in which these signals act. In the past grant period the projects in this orogram investigated the central and peripheral actions of leptin. This included the neural pathways activated by leptin and the cellular pathways engaged by leptin in the CMS and skeletal muscle. We also examined the effects of manipulation of leptin receptors in specific neuronal cell groups on energy homeostasis. We offer 5 individual proposals that utilize state of the art genetic, physiological, biochemical, and neuroanatomic techniques to investigate the actions of critical metabolic cues including leptin, ghrelin, and nutrient sensing in the regulation of food intake, energy expenditure, and body weight. These studies will extend from molecular mechanisms of action to systems based studies to understand the physiological importance of these hormones through specific neural circuits. Our proposal consists of 5 individual projects and 3 cores. Project 1 will use functional neuroanatomy to assess the hypothesis that the recently identified hormone ghrelin acts through similar pathways as leptin. Studies will critically test the role of AGRP/NPY neurons in mediating the important actions of ghrelin by generating and evaluating mice that express ghrelin receptors exclusively on AGRP/NPY neurons. Project 2 will assess the role of melanin concentrating hormone (MCH) in regulating energy expenditure through effects on sympathetic activity and resting energy expenditure and through effects on the dopamine system locomotor activity. Project 3 focuses exclusively on the arcuate nucleus (AGRP/NPY neurons and POMC neurons) and uses genetically engineered mice to test specific hypotheses regarding the role of two afferent signals, leptin (new Aim #1) and "lipid sensing" (new Aim #2), and two efferent signals, glutamate and GABA (new Aim #3) in regulating energy homeostasis. Project 4 will assess the biologic significance of the AMP-activated protein kinase (AMPK) pathway in mediating the central and peripheral effects of leptin on energy homeostasis. This will include determining if impaired leptin action on AMPK contributes to "leptin resistance" in obesity;how the AMPK pathway integrates with other leptin signaling pathways;and which neuronal circuits mediate the effects of AMPK on food intake and energy homeostasis. Project 5 will examine the role of suppressor of cytokine signaling 3 (SOCS3) in the neuronal actions of both leptin and insulin. This will involve studies of leptin and insulin signaling and physiologic actions in mice with generalized neuronal deletion of SOCS3, and deletion or overexpression of SOCS3 in AgRP and POMC neurons. Core A will be an administrative core. Core B will be a Neuroanatomy Core and Core C will be a Physiology Core. Together, these projects will continue to leverage the collaborative efforts and expertise of investigators in Boston and will greatly increase the understanding of the central circuits regulating body weight.
Funding Period: ----------------1999 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Neuronal circuits that regulate feeding behavior and metabolism
    Jong Woo Sohn
    Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    Trends Neurosci 36:504-12. 2013
  2. ncbi Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice
    Pavlos Pissios
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Biol Psychiatry 64:184-91. 2008
  3. ncbi Dietary fatty acids differentially regulate production of TNF-alpha and IL-10 by murine 3T3-L1 adipocytes
    Richard L Bradley
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Obesity (Silver Spring) 16:938-44. 2008
  4. pmc Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
    Jennifer W Hill
    Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 118:1796-805. 2008
  5. doi The long reach of leptin
    Eleftheria Maratos-Flier
    Nat Med 14:604-6. 2008
  6. pmc The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress
    Michael Lutter
    Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390 9077, USA
    Nat Neurosci 11:752-3. 2008
  7. pmc Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice
    Richard L Bradley
    Dept of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Am J Physiol Endocrinol Metab 295:E586-94. 2008
  8. pmc Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight
    Ren Zhang
    Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Endocrinology 149:5654-61. 2008
  9. pmc Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression
    J T Willie
    Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 8584, USA
    Neuroscience 156:819-29. 2008
  10. pmc Brain SIRT1: anatomical distribution and regulation by energy availability
    Giorgio Ramadori
    Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9077, USA
    J Neurosci 28:9989-96. 2008

Scientific Experts

  • Anthony N van den Pol
  • Guo Ping Shi
  • Pavlos Pissios
  • Joel K Elmquist
  • Barbara B Kahn
  • Bradford B Lowell
  • Eleftheria Maratos-Flier
  • Jeffrey M Zigman
  • Charlotte E Lee
  • Yong Xu
  • Roberto Coppari
  • Lora K Heisler
  • Kevin W Williams
  • Jennifer W Hill
  • Juli E Jones
  • Nina Balthasar
  • Bingzhong Xue
  • Jeffrey S Flier
  • Ichiro Sakata
  • Qingchun Tong
  • Michael A Cowley
  • Richard L Bradley
  • Adam R Kennedy
  • Thomas Pulinilkunnil
  • Makoto Fukuda
  • Jason G Anderson
  • Ren Zhang
  • Kenji Asakura
  • Frederic Preitner
  • Kendra K Bence
  • Michael K Badman
  • Thierry Alquier
  • Chianping Ye
  • Harveen Dhillon
  • Ligang Zhou
  • Jong Woo Sohn
  • Nadege Briancon
  • Odile D Peroni
  • Dong Kong
  • Junji Kawashima
  • Lewis C Cantley
  • Sherry A Rovinsky
  • Benjamin G Neel
  • Sherri Osborne-Lawrence
  • Justin Y Jeon
  • S C Robins
  • David E G McNay
  • Yossi Dagon
  • Anthony N Hollenberg
  • Kim Loh
  • Jamie C Harris
  • Kristen R Vella
  • Franck Chiappini
  • E Maratos-Flier
  • Eric D Berglund
  • Zhenggang Yang
  • Jens C Bruning
  • Huamei He
  • William L Holland
  • Anna Lee
  • Philipp E Scherer
  • Jen Chieh Chuang
  • David P Olson
  • Carol F Elias
  • Youki Tsuji
  • You Ree Cho
  • Michael M Scott
  • Michelle Choi
  • Jian Liu
  • Brian Choi
  • Ji Luo
  • Gerald I Shulman
  • Giorgio Ramadori
  • Esther van de Wall
  • Michael Lutter
  • J T Willie
  • Streamson Chua
  • Noboru Furukawa
  • Fen Fen Liu
  • Rebecca Leshan
  • Cem Z Gorgun
  • Mirela Delibegovic
  • Martin G Myers
  • Joel Elmquist
  • Jeffrey M Friedman
  • Gokhan S Hotamisligil
  • Rory J McCrimmon
  • Masa Katic
  • Heike Munzberg
  • Jia Yu

Detail Information

Publications59

  1. pmc Neuronal circuits that regulate feeding behavior and metabolism
    Jong Woo Sohn
    Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    Trends Neurosci 36:504-12. 2013
    ..This review integrates recently defined cellular mechanisms and neural circuits relevant to the regulation of feeding behavior, energy expenditure, and glucose homeostasis by metabolic signals. ..
  2. ncbi Dysregulation of the mesolimbic dopamine system and reward in MCH-/- mice
    Pavlos Pissios
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Biol Psychiatry 64:184-91. 2008
    ....
  3. ncbi Dietary fatty acids differentially regulate production of TNF-alpha and IL-10 by murine 3T3-L1 adipocytes
    Richard L Bradley
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
    Obesity (Silver Spring) 16:938-44. 2008
    ..Effects on nuclear factor-kappaB (NF-kappaB), a key transcriptional activator of the inflammatory cascade, and suppressor of cytokine signaling 3 (SOCS-3), a negative regulator of cytokine signaling, were also determined...
  4. pmc Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice
    Jennifer W Hill
    Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 118:1796-805. 2008
    ....
  5. doi The long reach of leptin
    Eleftheria Maratos-Flier
    Nat Med 14:604-6. 2008
  6. pmc The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress
    Michael Lutter
    Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390 9077, USA
    Nat Neurosci 11:752-3. 2008
    ..Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress...
  7. pmc Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice
    Richard L Bradley
    Dept of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Am J Physiol Endocrinol Metab 295:E586-94. 2008
    ..These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD...
  8. pmc Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight
    Ren Zhang
    Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Endocrinology 149:5654-61. 2008
    ..These results suggest that Socs3 in SF1 neurons negatively regulates leptin signaling and plays important roles in mediating leptin sensitivity, glucose homeostasis, and energy expenditure...
  9. pmc Abnormal response of melanin-concentrating hormone deficient mice to fasting: hyperactivity and rapid eye movement sleep suppression
    J T Willie
    Department of Molecular Genetics, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 8584, USA
    Neuroscience 156:819-29. 2008
    ..When combined with caloric restriction, the treatment of healthy, obese subjects with this compound resulted in some subjects experiencing vivid dreams and sleep disturbances...
  10. pmc Brain SIRT1: anatomical distribution and regulation by energy availability
    Giorgio Ramadori
    Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9077, USA
    J Neurosci 28:9989-96. 2008
    ..Collectively, our findings establish the distribution of Sirt1 mRNA throughout the neuraxis and suggest a previously unrecognized role of brain SIRT1 in regulating energy homeostasis...
  11. pmc 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis
    Yong Xu
    Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Neuron 60:582-9. 2008
    ..The findings also highlight the physiological relevance of the 5-HT2CR-melanocortin circuitry in the long-term regulation of energy balance...
  12. pmc Monitoring FoxO1 localization in chemically identified neurons
    Makoto Fukuda
    Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9077, USA
    J Neurosci 28:13640-8. 2008
    ..Thus, our FoxO1GFP mouse provides a tool for monitoring the status of PI3K-Akt signaling in a cell-specific manner under physiological and pathophysiological conditions...
  13. pmc Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance
    Qingchun Tong
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Ave, Boston, Massachusetts 02215, USA
    Nat Neurosci 11:998-1000. 2008
    ..These mice are lean, resistant to obesity and have an attenuated hyperphagic response to ghrelin. Thus, GABA release from AgRP neurons is important in regulating energy balance...
  14. pmc A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss
    Michael K Badman
    Division of Endocrinology, Beth Israel Deaconess Medical Center, Center for Life Sciences, 7th Fl, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Endocrinol Metab 297:E1197-204. 2009
    ..These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss...
  15. ncbi α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors
    S C Robins
    MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK
    Nat Commun 4:2049. 2013
    ..Our results suggest that α-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation...
  16. pmc Ca2+/calmodulin-dependent protein kinase kinase is not involved in hypothalamic AMP-activated protein kinase activation by neuroglucopenia
    Junji Kawashima
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e36335. 2012
    ..Importantly, activation of hypothalamic α1 and α2-AMPK by 2DG was not affected by ICV pre-administration of STO. In conclusion, activation of hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK...
  17. pmc p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake
    Yossi Dagon
    Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 16:104-12. 2012
    ..This discovery has broad biologic implications since mTOR-p70S6 kinase and AMPK have multiple, fundamental and generally opposing cellular effects that regulate metabolism, cell growth, and development...
  18. pmc Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion
    Esther van de Wall
    Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 12461, USA
    Endocrinology 149:1773-85. 2008
    ....
  19. ncbi Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice
    Masa Katic
    Joslin Diabetes Center, One Joslin Place and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Aging Cell 6:827-39. 2007
    ..Together, these data suggest that maintenance of mitochondrial activity and metabolic rates in adipose tissue may be important contributors to the increased lifespan of the FIRKO mouse...
  20. ncbi Diet-induced obesity alters AMP kinase activity in hypothalamus and skeletal muscle
    Tonya L Martin
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 281:18933-41. 2006
    ..Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states...
  21. pmc AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues
    Bingzhong Xue
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Research North 380C, Boston, MA 02215, USA
    J Physiol 574:73-83. 2006
    ..The AMPK pathway in the hypothalamus and peripheral tissues coordinately integrates inputs from multiple hormones, peptides and nutrients to maintain energy homeostasis...
  22. ncbi MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance
    Justin Y Jeon
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Diabetes 55:428-34. 2006
    ..In contrast, expression of Sir2 was unchanged. In aggregate, these findings suggest that MCH ablation improves the long-term outcome for several indicators of the aging process...
  23. ncbi Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis
    Harveen Dhillon
    Department of Medicine, Division of Endocrinology, Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA
    Neuron 49:191-203. 2006
    ..These results reveal a critical role for leptin action on VMH neurons...
  24. ncbi Expression of ghrelin receptor mRNA in the rat and the mouse brain
    Jeffrey M Zigman
    Department of Medicine and Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Comp Neurol 494:528-48. 2006
    ....
  25. ncbi Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions
    Pavlos Pissios
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Endocr Rev 27:606-20. 2006
    ....
  26. pmc Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony
    Mark A Herman
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Clin Invest 116:1767-75. 2006
    ..Here we review the roles of glucose and its metabolites as signaling molecules and the diverse physiologic mechanisms for glucose sensing...
  27. ncbi Neuronal PTP1B regulates body weight, adiposity and leptin action
    Kendra K Bence
    Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, NRB 1030, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Med 12:917-24. 2006
    ..Thus, PTP1B regulates body mass and adiposity primarily through actions in the brain. Furthermore, neuronal PTP1B regulates adipocyte leptin production and probably is essential for the development of leptin resistance...
  28. ncbi Serotonin reciprocally regulates melanocortin neurons to modulate food intake
    Lora K Heisler
    Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge, CB2 2QQ, United Kingdom
    Neuron 51:239-49. 2006
    ....
  29. ncbi Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia
    Thierry Alquier
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, MA 02215, USA
    Endocrinology 148:1367-75. 2007
    ..Furthermore, impaired or delayed AMPK activation in specific hypothalamic regions may play a critical role in the etiology of HAAF...
  30. ncbi Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation
    Lora K Heisler
    Department of Clinical Biochemistry, Addenbrooke s Hospital and the University of Cambridge, Cambridge CB2 2QR, United Kingdom
    J Neurosci 27:6956-64. 2007
    ....
  31. ncbi Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states
    Michael K Badman
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Cell Metab 5:426-37. 2007
    ..These findings identify hepatic FGF21 as a critical regulator of lipid homeostasis and identify a physiological role for this hepatic hormone...
  32. pmc Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia
    Qingchun Tong
    Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
    Cell Metab 5:383-93. 2007
    ..Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia...
  33. pmc Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways
    Ligang Zhou
    Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK
    Cell Metab 6:398-405. 2007
    ....
  34. ncbi A high-fat, ketogenic diet induces a unique metabolic state in mice
    Adam R Kennedy
    Division of Endocrinology, Departmentof Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Endocrinol Metab 292:E1724-39. 2007
    ..Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss...
  35. ncbi Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling
    Heike Munzberg
    Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Neurosci 27:69-74. 2007
    ....
  36. pmc More than satiety: central serotonin signaling and glucose homeostasis
    Pavlos Pissios
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 6:345-7. 2007
    ..As reported by Zhou et al. (2007) in this issue of Cell Metabolism, they also have unexpected effects on peripheral glucose homeostasis independent of food intake and body weight...
  37. pmc Glucose stimulation of hypothalamic MCH neurons involves K(ATP) channels, is modulated by UCP2, and regulates peripheral glucose homeostasis
    Dong Kong
    Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 12:545-52. 2010
    ..Combined, the glucose-excited neurons are likely to play key, previously unexpected roles in regulating blood glucose...
  38. pmc 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver
    Yong Xu
    Division of Hypothalamic Research and Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA
    Nat Neurosci 13:1457-9. 2010
    ..Our findings indicate that 5-HT(2C)Rs expressed by POMC neurons are physiologically relevant regulators of insulin sensitivity and glucose homeostasis in the liver...
  39. pmc A serotonin and melanocortin circuit mediates D-fenfluramine anorexia
    Yong Xu
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Neurosci 30:14630-4. 2010
    ..Thus, our results identify a neurochemically defined neural circuit through which D-Fen influences appetite and thereby indicate that this 5-HT(2C)R/POMC-MC4R/SIM1 circuit may yield a more refined target to exploit for weight loss...
  40. pmc Lack of cAMP-response element-binding protein 1 in the hypothalamus causes obesity
    Franck Chiappini
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 286:8094-105. 2011
    ..Thus CREB1 may affect other pathways that are implicated in the regulation of body weight...
  41. pmc Adrenergic regulation of AMP-activated protein kinase in brown adipose tissue in vivo
    Thomas Pulinilkunnil
    Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 286:8798-809. 2011
    ..Furthermore, AMPK α Ser(485/491) phosphorylation may be a novel mechanism to inhibit AMPK activity in vivo and alter its biological effects...
  42. pmc Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance
    Kim Loh
    Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia
    Cell Metab 14:684-99. 2011
    ..Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity...
  43. pmc NPY and MC4R signaling regulate thyroid hormone levels during fasting through both central and peripheral pathways
    Kristen R Vella
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 14:780-90. 2011
    ..Thus, these signaling pathways play a key role in the communication of fasting signals to reduce thyroid hormone levels both centrally and through a peripheral hepatic circuit...
  44. pmc Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice
    David E G McNay
    Beth Israel Deaconess Medical Center, Division of Endocrinology, Diabetes, and Metabolism, Center for Life Sciences, Boston, Massachusetts, USA
    J Clin Invest 122:142-52. 2012
    ..This insight has important implications for our understanding of nutritional regulation of energy balance and brain function...
  45. pmc Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility
    Jennifer W Hill
    Center for Diabetes and Endocrine Research, Department of Physiology and Pharmacology, College of Medicine, The University of Toledo, Toledo, OH 43614, USA
    Cell Metab 11:286-97. 2010
    ..We conclude that direct action of insulin and leptin on POMC neurons is required to maintain normal glucose homeostasis and reproductive function...
  46. pmc Combined neural inactivation of suppressor of cytokine signaling-3 and protein-tyrosine phosphatase-1B reveals additive, synergistic, and factor-specific roles in the regulation of body energy balance
    Nadege Briancon
    Division of Endocrinology, Diabetes, and Metabolism, Center for Life Sciences, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Diabetes 59:3074-84. 2010
    ....
  47. pmc Macrophage alpha1 AMP-activated protein kinase (alpha1AMPK) antagonizes fatty acid-induced inflammation through SIRT1
    Zhenggang Yang
    Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 285:19051-9. 2010
    ..Our study defines a novel role for AMPK in bridging the signaling between nutrient metabolism and inflammation...
  48. pmc Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons
    Anthony N van den Pol
    Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    J Neurosci 29:4622-39. 2009
    ....
  49. pmc Reduced adiposity and high-fat diet-induced adipose inflammation in mice deficient for phosphodiesterase 4B
    Ren Zhang
    Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
    Endocrinology 150:3076-82. 2009
    ....
  50. pmc Characterization of a novel ghrelin cell reporter mouse
    Ichiro Sakata
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9077, USA
    Regul Pept 155:91-8. 2009
    ..We suggest that these novel ghrelin-hrGFP transgenic mice will serve as useful tools to better understand ghrelin cell physiology...
  51. pmc Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells
    Ichiro Sakata
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9077, USA
    Am J Physiol Endocrinol Metab 297:E134-41. 2009
    ..We also demonstrate that GOAT is the only member of the MBOAT family whose expression is highly enriched within gastric ghrelin cells and whose whole body distribution mirrors that of ghrelin...
  52. pmc Animals models of MCH function and what they can tell us about its role in energy balance
    Pavlos Pissios
    Beth Israel Deaconess Medical Center, Boston, MA 02446, United States
    Peptides 30:2040-4. 2009
    ..Emphasis is given on the discrepancies between the genetic and pharmacologic models of MCHR1 inactivation. We propose some solutions to resolve these discrepancies and discuss some future directions in MCH research...
  53. pmc Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues
    Bingzhong Xue
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Mol Cell Biol 29:4563-73. 2009
    ..Therefore, the mechanism by which PTP1B regulates adiposity and leptin sensitivity likely involves the coordinated regulation of AMPK in hypothalamus and peripheral tissues...
  54. pmc Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice
    Jian Liu
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 15:940-5. 2009
    ..Our results showing reduced obesity and diabetes in mice treated with clinically available mast cell-stabilizing agents suggest the potential of developing new therapies for these common human metabolic disorders...
  55. pmc Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis
    Jennifer W Hill
    Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9077, USA
    Endocrinology 150:4874-82. 2009
    ..These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis...
  56. pmc Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis
    Frederic Preitner
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
    Am J Physiol Endocrinol Metab 297:E1420-9. 2009
    ..In conclusion, long-term therapy with FEN partially prevents or reverses obesity, insulin resistance, and hepatic steatosis in mice on HFD. The anti-adiposity effects are independent of the RBP4 lowering effect...
  57. pmc Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake
    David P Olson
    Division of Endocrinology, Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:7598-603. 2010
    ..The limited impact of Acc2 deletion on energy balance raises the possibility that selective pharmacological inhibition of Acc2 for the treatment of obesity may be ineffective...
  58. pmc Leptin targets in the mouse brain
    Michael M Scott
    Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Comp Neurol 514:518-32. 2009
    ..Thus, we provide data supporting the use of the LepRb-IRES-Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor...