Leptin Suppresses the Rewarding Effects of Running via STAT3 Signaling in Dopamine Neurons

Cell Metabolism
Maria Fernanda A FernandesStephanie Fulton

Abstract

The adipose hormone leptin potently influences physical activity. Leptin can decrease locomotion and running, yet the mechanisms involved and the influence of leptin on the rewarding effects of running ("runner's high") are unknown. Leptin receptor (LepR) signaling involves activation of signal transducer and activator of transcription-3 (STAT3), including in dopamine neurons of the ventral tegmental area (VTA) that are essential for reward-relevant behavior. We found that mice lacking STAT3 in dopamine neurons exhibit greater voluntary running, an effect reversed by viral-mediated STAT3 restoration. STAT3 deletion increased the rewarding effects of running whereas intra-VTA leptin blocked it in a STAT3-dependent manner. Finally, STAT3 loss-of-function reduced mesolimbic dopamine overflow and function. Findings suggest that leptin influences the motivational effects of running via LepR-STAT3 modulation of dopamine tone. Falling leptin is hypothesized to increase stamina and the rewarding effects of running as an adaptive means to enhance the pursuit and procurement of food.

References

Feb 1, 1985·Medicine and Science in Sports and Exercise·W P Morgan
Oct 1, 1971·Journal of Comparative and Physiological Psychology·G Collier, E Hirsch
Jul 28, 1995·Science·M A PelleymounterF Collins
Jul 18, 1996·Nature·R S AhimaJ S Flier
Nov 1, 1995·Journal of Psychosomatic Research·C DavisD Ratusny
Sep 16, 1999·The New England Journal of Medicine·I S FarooqiS O'Rahilly
Dec 30, 1999·Science·S FultonP Shizgal
May 9, 2000·The Journal of Biological Chemistry·A S BanksM G Myers
Jul 6, 2000·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·A W ThorburnG Morahan
Mar 20, 2002·Pharmacology, Biochemistry, and Behavior·Bow Tong LettGillian Flynn
May 6, 2003·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Carolyn A Buckley, Jill E Schneider
Apr 1, 1954·Journal of Comparative and Physiological Psychology·J KAGAN, M BERKUN
Nov 7, 2003·The Journal of Clinical Endocrinology and Metabolism·Kristian HoltkampJohannes Hebebrand
Nov 20, 2003·Neuroscience Letters·Héctor Vargas-PérezJosé Luis Díaz
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Julio LicinioMa-Li Wong
Jul 6, 2004·Physiology & Behavior·J M Overton, T D Williams
Jul 28, 2004·Neuroscience Letters·Héctor Vargas-PérezJosé-Luis Díaz
Nov 19, 2004·Nature·Dennis M Bramble, Daniel E Lieberman
Jul 26, 2006·Genesis : the Journal of Genetics and Development·Cristina M BäckmanAndreas C Tomac
Sep 20, 2006·Neuron·Jonathan D HommelRalph J DiLeone
Sep 20, 2006·Neuron·Stephanie FultonJeffrey S Flier
Oct 3, 2007·Physiological and Biochemical Zoology : PBZ·Isabelle GirardTheodore Garland
Dec 8, 2007·Behavioural Brain Research·Yang-Ho ChoiClifton A Baile
May 15, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brenda M GeigerEmmanuel N Pothos
Oct 4, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Erin Keen-Rhinehart, Timothy J Bartness
Apr 8, 2009·The Journal of Comparative Neurology·Michael M ScottJoel K Elmquist
Jun 6, 2009·Cell Metabolism·Lihong HuoChristian Bjørbaek
Jun 13, 2009·Behavioural Brain Research·Amy M KnabJ Timothy Lightfoot
Oct 14, 2009·Frontiers in Neuroendocrinology·Stephanie Fulton
Feb 17, 2010·Behavioural Brain Research·Wendy Foulds MathesDaniel Pomp
Nov 3, 2010·Biological Psychiatry·Jon F DavisStephen C Benoit
Nov 11, 2010·American Journal of Physiology. Endocrinology and Metabolism·Gregory J MortonBrent E Wisse
Nov 13, 2010·Behavioural Brain Research·Benjamin N GreenwoodMonika Fleshner
Dec 31, 2010·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Linda A W VerhagenRoger A H Adan
Jan 15, 2011·The Journal of Biological Chemistry·Stephanie FultonLouis-Eric Trudeau
Jun 10, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Timothy J BartnessB J Teubner
Nov 15, 2011·PloS One·Richard TrinkoRalph J DiLeone
Nov 15, 2011·Nature Neuroscience·Ana I DomingosJeffrey Friedman
Jan 21, 2012·International Journal of Sports Medicine·T BobbertS Diederich
Dec 15, 2012·Biological Psychiatry·Sarah DubreucqFrancis Chaouloff

❮ Previous
Next ❯

Citations

Jun 3, 2016·Integrative and Comparative Biology·Theodore GarlandWendy Saltzman
Jul 23, 2016·Frontiers in Neuroscience·Philip GorwoodJacques Epelbaum
Feb 19, 2016·The International Journal of Neuropsychopharmacology·Stéphanie AugusteStephanie Fulton
Oct 22, 2016·Annals of the New York Academy of Sciences·Alexandre Caron, Denis Richard
Jun 19, 2016·Journal of Neuroendocrinology·A P BorrowR Yunes
Feb 8, 2018·Frontiers in Neuroanatomy·Xuefeng YuanLaurent Gautron
Dec 7, 2017·Endocrinology·Stephanie E Simonds, Michael A Cowley
Dec 23, 2017·Molecular Neurobiology·Mei LiuHyoung-Chun Kim
Jan 19, 2018·Scientific Reports·Ferran JardíDirk Vanderschueren
Mar 26, 2019·Endocrinology·Luis Leon MercadoLaurent Gautron
Sep 1, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Cecile HryhorczukStephanie Fulton
Aug 11, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gregory N RuegseggerFrank W Booth
Dec 4, 2019·Nature Communications·Harry MacKayRobert A Waterland
Jun 8, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joram D MulLaurie J Goodyear
Oct 4, 2018·European Eating Disorders Review : the Journal of the Eating Disorders Association·Marta G Novelle, Carlos Diéguez
Apr 11, 2018·Frontiers in Endocrinology·Stefanie FruhwürthKevin Jon Williams
Jun 9, 2020·The Journal of Clinical Investigation·R N LippertJ C Brüning
Jun 3, 2017·Frontiers in Endocrinology·Ryan Michael Cassidy, Qingchun Tong
May 11, 2018·The Journal of Endocrinology·Ferran JardíFrank Claessens
Apr 6, 2019·Frontiers in Psychiatry·Rafaela Carneiro CordeiroAndre F Carvalho
Oct 7, 2020·Addiction Biology·Maria-Carmen MedranoFrancis Chaouloff
Mar 18, 2021·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Jing ZhangFa-Dao Tai
Sep 25, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Imane HurelFrancis Chaouloff
Oct 28, 2019·Trends in Endocrinology and Metabolism : TEM·Philibert DuriezVirginie Tolle
Apr 20, 2021·Brain, Behavior, and Immunity·Maria F FernandesStephanie Fulton
Jun 3, 2021·International Journal of Molecular Sciences·Elvira S SandinMarkus Schwaninger
Sep 21, 2020·Biological Psychiatry·Jeff A BeelerNesha S Burghardt

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric condition characterized by severe weight loss and secondary problems associated with malnutrition. Here is the latest research on AN.

Basal Forebrain & Food Avoidance

Neurons in the basal forebrain play specific roles in regulating feeding. Here are the latest discoveries pertaining to the basal forebrain and food avoidance.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.