title: Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity.
abstract: Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gisignaling in these neurons increased activity in obese mice. Surprisingly, although mice with low D2Rs were less active, they were not more vulnerable to diet-induced weight gain than control mice. We conclude that deficits in striatal D2R signaling contribute to physical inactivity in obesity, but inactivity is more a consequence than a cause of obesity.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Friend
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Kavya
authors.initials: K
authors.lastname: Devarakonda
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: O'Neal
authors.affiliation: Section of Molecular Neurobiology, Eunice Shriver Kennedy National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Skirzewski
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papazoglou
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Alanna R
authors.initials: AR
authors.lastname: Kaplan
authors.affiliation: National Institute of Mental Health, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Jeih-San
authors.initials: JS
authors.lastname: Liow
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Juen
authors.initials: J
authors.lastname: Guo
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Sushil G
authors.initials: SG
authors.lastname: Rane
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, C1428ADN Buenos Aires, Argentina; Department of Physiology, Molecular and Cellular Biology, FCEN, Universidad de Buenos Aires, C1428EGA Buenos Aires, Argentina; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rubinstein
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Alvarez
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Hall
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA; National Institute on Drug Abuse, National Institutes of Health, Bethesda MD 20892, USA. Electronic address: lex.kravitz@nih.gov.
authors.forename: Alexxai V
authors.initials: AV
authors.lastname: Kravitz
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000503:physiopathology*; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009068:Movement; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010805:Physical Conditioning, Animal; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D015430:Weight Gain
chemical_list: D017448:Receptors, Dopamine D2
keywords: D2; dopamine; exercise; obese; obesity; physical activity; striatum; weight loss