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Cell Metab. 2017 Feb 7;25(2):312-321. doi: 10.1016/j.cmet.2016.12.001. Epub 2016 Dec 29.

Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity.

Author information

1
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20892, USA.
2
Section of Molecular Neurobiology, Eunice Shriver Kennedy National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892, USA.
3
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda MD 20892, USA.
4
National Institute of Mental Health, National Institutes of Health, Bethesda MD 20892, USA.
5
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.
6
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.

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 Gi signaling 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.

KEYWORDS:

D2; dopamine; exercise; obese; obesity; physical activity; striatum; weight loss

PMID:
28041956
PMCID:
PMC5299005
DOI:
10.1016/j.cmet.2016.12.001
[Indexed for MEDLINE]
Free PMC Article

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