Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors

Kyu Seok Kim, Ye Ran Yoon, Hyo Jin Lee, Sehyoun Yoon, Sa Yong Kim, Seung Woo Shin, Juan Ji An, Min Seon Kim, Se Young Choi, Woong Sun, Ja Hyun Baik

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Abstract

The dopamine D2 receptor (D2R) plays a critical role in diverse neurophysiological functions. D2R knock-out mice (D2R-/-) show reduced food intake and body weight while displaying an increased basal energy expenditure level, compared with their wild type littermates. Thus, these mice show a lean phenotype. D2R-/- mice displayed increased leptin sensitivity, and leptin injection induced increased phosphorylation of the hypothalamic signal transducer and activator of transcription 3 (STAT3) in D2R-/- mice relative to wild type littermates. Using double immunofluorescence histochemistry, we have demonstrated that D2Rs are present in leptin-sensitive STAT3-positive cells in the arcuate nucleus of the hypothalamus and that leptin injection induces STAT3 phosphorylation in hypothalamic neurons expressing D2Rs. Stimulation of D2R by the D2R agonist quinpirole suppressed the leptin-induced STAT3 phosphorylation and nuclear trans-localization of phospho-STAT3 in the hypothalamus of wild type mice. However, this regulation was not detected in the D2R-/- mice. Treatment of D2R agonist and antagonist could modulate the leptin-induced food intake and body weight changes in wild type mice but not in D2R-/- mice. Together, our findings suggest that the interaction between the dopaminergic system and leptin signaling in hypothalamus is important in control of energy homeostasis.

Original languageEnglish
Pages (from-to)8905-8917
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number12
DOIs
Publication statusPublished - 2010 Mar 19

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, K. S., Yoon, Y. R., Lee, H. J., Yoon, S., Kim, S. Y., Shin, S. W., An, J. J., Kim, M. S., Choi, S. Y., Sun, W., & Baik, J. H. (2010). Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors. Journal of Biological Chemistry, 285(12), 8905-8917. https://doi.org/10.1074/jbc.M109.079590