α-MSH overexpression in the nucleus tractus solitarius decreases fat mass and elevates heart rate.
The POMC pathway is involved in the regulation of energy and cardiovascular homeostasis in the hypothalamus and the brain stem. Although the acute effects of POMC-derived peptides in different brain locations have been elucidated, the chronic site-specific effects of distinct peptides remain to be studied. To this end, we used a lentiviral gene delivery vector to study the long-term effects of α-MSH in the nucleus tractus solitarius (NTS) of the brain stem. The α-MSH vector (LVi-α-MSH-EGFP) based on the N-terminal POMC sequence and a control vector (LVi-EGFP) were delivered into the NTS of C57BL/6N male mice fed on a western diet. Effects on body weight and composition, feeding, glucose metabolism, and hemodynamics by telemetric analyses were studied during the 12-week follow-up. The LVi-α-MSH-EGFP-treated mice had a significantly smaller gain in the fat mass compared with LVi-EGFP-injected mice. There was a small initial decrease in food intake and no differences in the physical activity. Glucose metabolism was not changed compared with the control. LVi-α-MSH-EGFP increased the heart rate (HR), which was attenuated by adrenergic blockade suggesting an increased sympathetic activity. Reduced response to muscarinic blockade suggested a decreased parasympathetic activity. Fitting with sympathetic activation, LVi-α-MSH-EGFP treatment reduced urine secretion. Thus, the results demonstrate that long-term α-MSH overexpression in the NTS attenuates diet-induced obesity. Modulation of autonomic nervous system tone increased the HR and most probably contributed to an anti-obesity effect. The results underline the key role of NTS in the α-MSH-induced long-term effects on adiposity and in regulation of sympathetic and parasympathetic activities.
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, FinlandDepartment of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, FinlandDepartment of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland.
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Eerola
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland.
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Rinne
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland.
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Penttinen
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, FinlandDepartment of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland.
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Vähätalo
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, FinlandDepartment of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland.
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Savontaus
Department of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, FinlandDepartment of PharmacologyDrug Development and Therapeutics and Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandTurku Centre for BiotechnologyUniversity of Turku, Turku, FinlandDrug Research Doctoral ProgramUniversity of Turku, Turku, FinlandHeart CenterTurku University Hospital and University of Turku, Turku, FinlandUnit of Clinical PharmacologyTurku University Hospital, Turku, Finland eriika.savontaus@utu.fi.
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Savontaus
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000517:prevention & control; D017552:Solitary Nucleus / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism*
D000521:alpha-MSH; D005947:Glucose
POMC; autonomic nervous system; blood pressure; brain stem; heart rate; lentivirus vector; obesity; parasympathetic; sympathetic; α-MSH