Leptin and insulin's hunger-suppressing and activity-promoting actions on hypothalamic neurons are well characterized, yet the mechanisms by which they modulate the midbrain dopamine system to influence energy balance remain less clear. A subset of midbrain dopamine neurons express receptors for leptin (Lepr) and insulin (Insr). Leptin-dopamine signaling reduces running reward and homecage activity. However, dopamine-specific deletion of Lepr does not affect body weight or food intake in mice. We hypothesized insulin-dopamine signaling might compensate for disrupted leptin-dopamine signaling. To investigate the degree to which insulin and leptin exert overlapping (i.e. redundant) versus discrete control over dopamine neurons, we generated transgenic male and female mice exhibiting dopamine-specific deletion of either Lepr (Lepr KO), Insr (Insr KO) or both Lepr and Insr (Dbl KO) and assessed their feeding behavior, voluntary activity, and energy expenditure compared to control mice. No differences in body weight, daily food intake, energy expenditure or hyperphagic feeding of palatable chow were observed between Lepr, Insr or Dbl KO mice and control mice. However, consistent with previous findings, Lepr KO (but not Insr or Dbl KO) male mice exhibited significantly increased running wheel activity compared to controls. These data demonstrate that insulin and leptin do not exert redundant control of dopamine neuron-mediated modulation of energy balance. Furthermore, our results indicate neither leptin nor insulin plays a critical role in the modulation of dopamine neurons regarding hedonic feeding behavior or anxiety-related behavior.
Pubmed ID: 30292429 RIS Download
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View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentionsThis polyclonal targets Tyrosine Hydroxylase
View all literature mentionsThis monoclonal targets INSR beta
View all literature mentionsMus musculus with name B6.129S4(FVB)-Insrtm1Khn/J from IMSR.
View all literature mentionsMus musculus with name B6.SJL-Slc6a3tm1.1(cre)Bkmn/J from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsMus musculus with name B6.129S4(FVB)-Insrtm1Khn/J from IMSR.
View all literature mentionsMus musculus with name B6.SJL-Slc6a3tm1.1(cre)Bkmn/J from IMSR.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets INSR beta
View all literature mentionsThis polyclonal targets Tyrosine Hydroxylase
View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentions