alpha-MSH overexpression in the nucleus tractus solitarius decreases fat mass and elevates heart rate

作者：Eerola K; Rinne P; Penttinen A M; Vahatalo L; Savontaus M; Savontaus E^*

来源：Journal of Endocrinology, 2014, 222(1): 123-136.

DOI：10.1530/JOE-14-0064

• obesity
• blood pressure
• heart rate
• brain stem
• alpha-MSH
• POMC
• lentivirus vector
• autonomic nervous system
• sympathetic
• parasympathetic

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 alpha-MSH in the nucleus tractus solitarius (NTS) of the brain stem. The alpha-MSH vector (LVi-alpha-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-alpha-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-alpha-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-alpha-MSH-EGFP treatment reduced urine secretion. Thus, the results demonstrate that long-term alpha-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 alpha-MSH-induced long-term effects on adiposity and in regulation of sympathetic and parasympathetic activities.

• 出版日期2014-7