Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white and brown adipose tissue without affecting skeletal muscle. In white adipocytes, mRNA expression of various fat storage–promoting enzymes such as lipoprotein lipase, acetyl-CoA carboxylase α, fatty acid synthase, and stearoyl-CoA desaturase–1 was markedly increased, while that of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase–1α, was decreased. In brown adipocytes, central ghrelin infusion resulted in lowered expression of the thermogenesis-related mitochondrial uncoupling proteins 1 and 3. These ghrelin effects were dose dependent, occurred independently from ghrelin-induced hyperphagia, and seemed to be mediated by the sympathetic nervous system. Additionally, the expression of some fat storage enzymes was decreased in ghrelin-deficient mice, which led us to conclude that central ghrelin is of physiological relevance in the control of cell metabolism in adipose tissue. These results unravel the existence of what we believe to be a new CNS-based neuroendocrine circuit regulating metabolic homeostasis of adipose tissue.
Claudia Theander-Carrillo, Petra Wiedmer, Philippe Cettour-Rose, Ruben Nogueiras, Diego Perez-Tilve, Paul Pfluger, Tamara R. Castaneda, Patrick Muzzin, Annette Schürmann, Ildiko Szanto, Matthias H. Tschöp, Françoise Rohner-Jeanrenaud
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Molecules (Basel, Switzerland) | 2018 |
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eLife | 2018 |
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Physiological reviews | 2017 |
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KD Bruce, A Zsombok, RH Eckel |
Frontiers in Endocrinology | 2017 |
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International journal of molecular sciences | 2017 |
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PloS one | 2017 |
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PloS one | 2017 |
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Experimental and therapeutic medicine | 2017 |
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Pharmacology & Therapeutics | 2016 |
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Endocrine | 2015 |
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Frontiers in Endocrinology | 2015 |
Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions
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International Journal of Endocrinology | 2015 |
Ghrelin – Physiological Functions and Regulation
MM Abdalla |
2015 | |
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Molecular Biology Reports | 2014 |
Ghrelin promotes hepatic lipogenesis by activation of mTOR-PPAR signaling pathway
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Proceedings of the National Academy of Sciences | 2014 |
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Scientific Reports | 2014 |
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European Journal of Nutrition | 2014 |
Hyperghrelinemia in Prader-Willi syndrome begins in early infancy long before the onset of hyperphagia
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American Journal of Medical Genetics Part A | 2014 |
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Endocrinology | 2013 |
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The FASEB Journal | 2013 |
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BM Filippi, MA Abraham, JT Yue, TK Lam |
Reviews in Endocrine and Metabolic Disorders | 2013 |
Structure and Physiological Actions of Ghrelin
C Delporte |
Scientifica | 2013 |
Long-term home cage activity scans reveal lowered exploratory behaviour in symptomatic female Rett mice
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Behavioural Brain Research | 2013 |
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Frontiers in neuroscience | 2013 |
Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation
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PloS one | 2013 |
Improved acylated ghrelin suppression at 2 years in obese patients with type 2 diabetes: effects of bariatric surgery vs standard medical therapy
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International Journal of Obesity | 2013 |
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Frontiers in neuroscience | 2013 |
Pmch-deficiency in rats is associated with normal adipocyte differentiation and lower sympathetic adipose drive
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PloS one | 2013 |
Both Acyl and Des-Acyl Ghrelin Regulate Adiposity and Glucose Metabolism via Central Nervous System Ghrelin Receptors
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Gastroenterology | 2012 |
Molecules affecting hypothalamic control of core body temperature in response to calorie intake
T Bartfai, B Conti |
Frontiers in Genetics | 2012 |
Ghrelin – A Pleiotropic Hormone Secreted from Endocrine X/A-Like Cells of the Stomach
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Frontiers in neuroscience | 2012 |
Sensing of Fatty Acids for Octanoylation of Ghrelin Involves a Gustatory G-Protein
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PloS one | 2012 |
Yin and Yang - the Gastric X/A-like Cell as Possible Dual Regulator of Food Intake
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Journal of Neurogastroenterology and Motility | 2012 |
Estradiol signaling in the regulation of reproduction and energy balance
K Sinchak, EJ Wagner |
Frontiers in Neuroendocrinology | 2012 |
Gastric Peptides and their Regulation of Hunger and Satiety
A Stengel, Y Taché |
Current Gastroenterology Reports | 2012 |
Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin
L Martins, D Fernández-Mallo, MG Novelle, MJ Vázquez, M Tena-Sempere, R Nogueiras, M López, C Diéguez |
PloS one | 2012 |
Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells
I Sakata, WM Park, AK Walker, PK Piper, JC Chuang, S Osborne-Lawrence, JM Zigman |
American journal of physiology. Endocrinology and metabolism | 2012 |
Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase
PB de Morentin, AJ Whittle, J Ferno, R Nogueiras, C Dieguez, A Vidal-Puig, M Lopez |
Diabetes | 2012 |
Acylation Type Determines Ghrelin's Effects on Energy Homeostasis in Rodents
KM Heppner, N Chaudhary, TD Müller, H Kirchner, KM Habegger, N Ottaway, DL Smiley, R DiMarchi, SM Hofmann, SC Woods, B Sivertsen, B Holst, PT Pfluger, D Perez-Tilve, MH Tschöp |
Endocrinology | 2012 |
Role of Ghrelin in the Pathophysiology of Eating Disorders: Implications for Pharmacotherapy
SC Cano, M Merkestein, KP Skibicka, SL Dickson, RA Adan |
CNS Drugs | 2012 |
The role of ghrelin-octanoyl-acyl-transferase in thermoregulation.
Heppner KM, Müller TD, Kirchner H, Perez-Tilve D, Pfluger PT, Tschöp MH, Hofmann SM |
Journal of Endocrinological Investigation | 2012 |
The HPA axis modulates the CNS melanocortin control of liver triacylglyceride metabolism
P Wiedmer, N Chaudhary, M Rath, CX Yi, G Ananthakrishnan, R Nogueiras, EK Wirth, H Kirchner, U Schweizer, W Jonas, C Veyrat-Durebex, F Rohner-Jeanrenaud, A Schurmann, HG Joost, MH Tschöp, D Perez-Tilve |
Physiology & Behavior | 2011 |
Hypothalamic AMP-activated protein kinase as a mediator of whole body energy balance
PB de Morentin, CR González, AK Saha, L Martins, C Diéguez, A Vidal-Puig, M Tena-Sempere, M López |
Reviews in Endocrine and Metabolic Disorders | 2011 |
Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging
X Ma, L Lin, G Qin, X Lu, M Fiorotto, VD Dixit, Y Sun, K Stadler |
PloS one | 2011 |
Obestatin as a regulator of adipocyte metabolism and adipogenesis
U Gurriarán-Rodríguez, O Al-Massadi, A Roca-Rivada, AB Crujeiras, R Gallego, M Pardo, LM Seoane, Y Pazos, FF Casanueva, JP Camiña |
Journal of Cellular and Molecular Medicine | 2011 |
Ghrelin-induced adiposity is independent of orexigenic effects
D Perez-Tilve, K Heppner, H Kirchner, SH Lockie, SC Woods, DL Smiley, M Tschöp, P Pfluger |
The FASEB Journal | 2011 |
Ghrelin Enhances Olfactory Sensitivity and Exploratory Sniffing in Rodents and Humans
J Tong, E Mannea, P Aimé, PT Pfluger, CX Yi, TR Castaneda, HW Davis, X Ren, S Pixley, S Benoit, K Julliard, SC Woods, TL Horvath, MM Sleeman, D D'Alessio, S Obici, R Frank, MH Tschöp |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2011 |
1 Peripheral ghrelin stimulates feeding behavior and positive energy balance in a sciurid hibernator
JE Healy, JL Bateman, CE Ostrom, GL Florant |
Hormones and Behavior | 2011 |
Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues
L Lin, PK Saha, X Ma, IO Henshaw, L Shao, BH Chang, ED Buras, Q Tong, L Chan, OP McGuinness, Y Sun |
Aging Cell | 2011 |
Ghrelin-induced hypothermia: a physiological basis but no clinical risk
P Wiedmer, F Strasser, TL Horvath, D Blum, R Dimarchi, T Lutz, A Schürmann, HG Joost, MH Tschöp, J Tong |
Physiology & Behavior | 2011 |
The Central Sirtuin 1/p53 Pathway Is Essential for the Orexigenic Action of Ghrelin
DA Velasquez, G Martinez, A Romero, MJ Vazquez, KD Boit, IG Dopeso-Reyes, M Lopez, A Vidal, R Nogueiras, C Dieguez |
Diabetes | 2011 |
Integrating GHS into the Ghrelin System
JD Veldhuis, CY Bowers |
International Journal of Peptides | 2010 |
Ghrelin: New Molecular Pathways Modulating Appetite and Adiposity
R Nogueiras, LM Williams, C Dieguez |
Obesity facts | 2010 |
Uncoupling protein-2 decreases the lipogenic actions of ghrelin
ZB Andrews, DM Erion, R Beiler, CS Choi, GI Shulman, TL Horvath |
Endocrinology | 2010 |
Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis
SD Jordan, AC Könner, JC Brüning |
Cellular and Molecular Life Sciences | 2010 |
Unacylated ghrelin rapidly modulates lipogenic and insulin signaling pathway gene expression in metabolically active tissues of GHSR deleted mice
PJ Delhanty, Y Sun, JA Visser, A Kerkwijk, M Huisman, WF van Ijcken, S Swagemakers, RG Smith, AP Themmen, AJ der Lely |
PloS one | 2010 |
Neuronal regulation of homeostasis by nutrient sensing
TK Lam |
Nature Medicine | 2010 |
Ghrelin and its potential in the treatment of eating/wasting disorders and cachexia
TD Müller, D Perez-Tilve, J Tong, PT Pfluger, MH Tschöp |
Journal of Cachexia, Sarcopenia and Muscle | 2010 |
Ghrelin in chronic kidney disease
WW Cheung, RH Mak |
International Journal of Peptides | 2010 |
Effect of Ghrelin on Glucose-Insulin Homeostasis: Therapeutic Implications
S Sangiao-Alvarellos, F Cordido |
International Journal of Peptides | 2010 |
Ghrelin effects on neuropeptides in the rat hypothalamus depend on fatty acid metabolism actions on BSX but not on gender
R Lage, MJ Vázquez, L Varela, AK Saha, A Vidal-Puig, R Nogueiras, C Diéguez, M López |
The FASEB Journal | 2010 |
Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: Role as regulators of food intake and body weight
A Stengel, M Goebel, L Wang, Y Taché |
Peptides | 2010 |
The metabolic response to the activation of the β- adrenergic receptor by salbutamol is amplified by acylated ghrelin
DH St-Pierre, A Benso, E Gramaglia, F Prodam, B Lucatello, V Ramella-Gigliardi, I Olivetti, M Tomelini, F Broglio |
Journal of Endocrinological Investigation | 2010 |
Ghrelin Induces Abdominal Obesity Via GHS-R-Dependent Lipid Retention
JS Davies, P Kotokorpi, SR Eccles, SK Barnes, PF Tokarczuk, SK Allen, HS Whitworth, IA Guschina, BA Evans, A Mode, JM Zigman, T Wells |
Molecular Endocrinology | 2009 |
Endocrine disrupters as obesogens
F Grün, B Blumberg |
Molecular and Cellular Endocrinology | 2009 |
Energy Homoeostasis: The Roles of Adipose Tissue-Derived Hormones, Peptide YY and Ghrelin
J Hall, R Roberts, N Vora |
Obesity facts | 2009 |
G Protein-Coupled Receptor 39 Deficiency Is Associated with Pancreatic Islet Dysfunction
B Holst, KL Egerod, C Jin, PS Petersen, MV Østergaard, J Hald, AM Sprinkel, J Størling, T Mandrup-Poulsen, JJ Holst, P Thams, C Ørskov, N Wierup, F Sundler, OD Madsen, TW Schwartz |
Endocrinology | 2009 |
Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity
R Nogueiras, D Pérez-Tilve, C Veyrat-Durebex, DA Morgan, L Varela, WG Haynes, JT Patterson, E Disse, PT Pfluger, M López, SC Woods, R DiMarchi, C Diéguez, K Rahmouni, F Rohner-Jeanrenaud, MH Tschöp |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2009 |
Effect of reducing hypothalamic ghrelin receptor gene expression on energy balance
YB Shrestha, K Wickwire, S Giraudo |
Peptides | 2009 |
Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion
S Sangiao-Alvarellos, MJ Vázquez, L Varela, R Nogueiras, AK Saha, F Cordido, M López, C Diéguez |
Endocrinology | 2009 |
Ghrelin and peptide YY in postpartum lactating and nonlactating women
DE Larson-Meyer, E Ravussin, L Heilbronn, L DeJonge |
The American journal of clinical nutrition | 2009 |
Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice
E Szentirmai, L Kapás, Y Sun, RG Smith, JM Krueger |
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology | 2009 |
The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice
E Szentirmai, L Kapás, Y Sun, RG Smith, JM Krueger |
Proceedings of the National Academy of Sciences | 2009 |
Direct effects of nutrients, acetylcholine, CCK, and insulin on ghrelin release from the isolated stomachs of rats
YB Shrestha, K Wickwire, SQ Giraudo |
Peptides | 2009 |
Evidence from knockout mice that peptide YY and neuropeptide Y enforce murine locomotion, exploration and ingestive behaviour in a circadian cycle- and gender-dependent manner
ME Edelsbrunner, H Herzog, P Holzer |
Behavioural Brain Research | 2009 |
Central leptin versus ghrelin: effects on bone marrow adiposity and gene expression
S Ambati, Q Li, S Rayalam, DL Hartzell, MA Della-Fera, MW Hamrick, CA Baile |
Endocrine | 2009 |
Evidence from knockout mice for distinct implications of neuropeptide-Y Y2 and Y4 receptors in the circadian control of locomotion, exploration, water and food intake
ME Edelsbrunner, E Painsipp, H Herzog, P Holzer |
Neuropeptides | 2009 |
Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults
JA Parnell, RA Reimer |
The American journal of clinical nutrition | 2009 |
Nutrition: Can ghrelin improve appetite in uremic wasting?
Carrero JJ, Stenvinkel P |
Nature reviews. Nephrology | 2009 |
Inducible gene silencing defines CNS insulin action as a major determinant of peripheral glucose and fat metabolism
Linda Koch1, F. Thomas Wunderlich1, Jost Seibler2, A. Christine Könner1, Brigitte Hampel1, Sigrid Irlenbusch1, Georg Brabant3, C. Ronald Kahn4, Frieder Schwenk2,5, Jens C. Brüning1 |
Journal of Clinical Investigation | 2008 |
The growth hormone-insulin-like growth factor-I axis in chronic kidney disease
RH Mak, WW Cheung, CT Roberts |
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society | 2008 |
Central nervous system regulation of energy metabolism: ghrelin versus leptin
R Nogueiras, MH Tschöp, JM Zigman |
Annals of the New York Academy of Sciences | 2008 |
Role of AMP-activated protein kinase in the control of appetite
B Kola |
Journal of Neuroendocrinology | 2008 |
Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study
F Strasser, TA Lutz, MT Maeder, B Thuerlimann, D Bueche, M Tschöp, K Kaufmann, B Holst, M Brändle, R Moos, R Demmer, T Cerny |
British Journal of Cancer | 2008 |
Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats
S Strassburg, SD Anker, TR Castaneda, L Burget, D Perez-Tilve, PT Pfluger, R Nogueiras, H Halem, JZ Dong, MD Culler, R Datta, MH Tschöp |
American journal of physiology. Endocrinology and metabolism | 2008 |
Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice
E Painsipp, T Wultsch, ME Edelsbrunner, RO Tasan, N Singewald, H Herzog, P Holzer |
Genes, Brain and Behavior | 2008 |
The central nervous melanocortin system directly controls peripheral lipid metabolism
Ruben Nogueiras, Petra Wiedmer, Diego Perez-Tilve, Christelle Veyrat-Durebex, Julia M. Keogh, Gregory M. Sutton, Paul T. Pfluger, Tamara R. Castaneda, Susanne Neschen, Susanna M. Hofmann, Philip N. Howles, Donald A. Morgan, Stephen C. Benoit, Ildiko Szanto, Brigitte Schrott, Annette Schürmann, Hans-Georg Joost, Craig Hammond, David Y. Hui, Stephen C. Woods, Kamal Rahmouni, Andrew A. Butler, I. Sadaf Farooqi, Stephen O’Rahilly, Françoise Rohner-Jeanrenaud & Matthias H. Tschöp |
Journal of Clinical Investigation | 2007 |
Intestinal Regulation of Glucose
Daniel J. Drucker |
Journal of Clinical Investigation | 2007 |
The hormonal control of food intake
AP Coll, IS Farooqi, S O'Rahilly |
Cell | 2007 |
Experimental gastritis in mice enhances anxiety in a gender-related manner
E Painsipp, T Wultsch, A Shahbazian, M Edelsbrunner, MC Kreissl, A Schirbel, E Bock, MA Pabst, CK Thoeringer, HP Huber, P Holzer |
Neuroscience | 2007 |
Ghrelin reduces hepatic mitochondrial fatty acid β oxidation
C Rigault, FL Borgne, B Georges, J Demarquoy |
Journal of Endocrinological Investigation | 2007 |
Ghrelin Effects on the Circadian System of Mice
PC Yannielli, PC Molyneux, ME Harrington, DA Golombek |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2007 |
In search of an effective obesity treatment: a shot in the dark or a shot in the arm?
JM Zigman, JK Elmquist |
Proceedings of the National Academy of Sciences | 2006 |