期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 308, 期 12, 页码 E1116-E1122出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00087.2015
关键词
obesity; mesolimbic; reward; islet amyloid polypeptide
资金
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [NIH-K01-DK-103804, NIH-R01-DK-096139]
- Penn Medicine Neuroscience Center pilot award
Peripheral coadministration of amylin and leptin produces enhanced suppression of food intake and body weight, but the central nuclei mediating these effects remain unclear. Because each of these peptides controls feeding via actions at the ventral tegmental area (VTA), we tested the hypothesis that the VTA is a site of action for the cooperative effects of leptin and amylin on energy balance control. First, we show that intra-VTA injection of amylin and leptin at doses of each peptide that are effective in reducing food intake and body weight when administered separately produces an enhanced suppression of feeding when administered in combination. We also demonstrate that subthreshold doses of both amylin and leptin cause significant hypophagia and body weight loss when coadministered into the VTA. Additionally, we provide evidence that VTA amylin receptor blockade significantly attenuates the ability of intra-VTA leptin to reduce feeding and body weight gain. Together, these data provide the first evidence that the VTA mediates the interaction of amylin and leptin to cooperatively promote negative energy balance.
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