delta-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice

作者：Kaneko Kentaro; Mizushige Takafumi; Miyazaki Yuri; Lazarus Michael; Urade Yoshihiro; Yoshikawa Masaaki; Kanamoto Ryuhei; Ohinata Kousaku^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2014, 306(4): R265-R272.

DOI：10.1152/ajpregu.00405.2013

• delta-opioid receptor
• food intake
• MC4
• CRF
• PGD(2)

The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central delta-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat diet intake as well. [D-Pen(2,5)]-enkephalin (DPDPE), an agonist selective for the delta-receptor, increased normal diet intake after central administration to nonfasted male mice. The orexigenic activity of DPDPE was inhibited by blockade of cyclooxygenase (COX)-2, lipocalin-type prostaglandin D synthase (L-PGDS), D-type prostanoid receptor 1 (DP1), and neuropeptide Y (NPY) receptor type 1 (Y-1) for PGD(2) and NPY, respectively, suggesting that this was mediated by the PGD(2)-NPY system. In contrast, DPDPE decreased high-fat diet intake in mice fed a high-fat diet. DPDPE-induced suppression of high-fat diet intake was blocked by antagonists of melanocortin 4 (MC4) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. These results suggest that central delta-opioid receptor activation suppresses high-fat diet intake via the MC-CRF system, independent of the orexigenic PGD(2) system. Furthermore, orally administered rubiscolin-6, an opioid peptide derived from spinach Rubisco, suppressed high-fat diet intake. This suppression was also blocked by centrally administered naltrindole, an antagonist for the delta-receptor, suggesting that rubiscolin-6 suppressed high-fat diet intake via activation of central delta-opioid receptor.

• 出版日期2014-2