title: δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice.
abstract: The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-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 δ-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 (DP(1)), and neuropeptide Y (NPY) receptor type 1 (Y1) 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 (MC(4)) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. These results suggest that central δ-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 δ-receptor, suggesting that rubiscolin-6 suppressed high-fat diet intake via activation of central δ-opioid receptor.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan;
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kaneko
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mizushige
authors.forename: Yuri
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Michael
authors.initials: M
authors.lastname: Lazarus
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Kanamoto
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D017465:Receptors, Opioid, delta; D011982:Receptors, Prostaglandin; C115461:SC 560; D013449:Sulfonamides; C527097:prostanoid D receptor 1, mouse; D020881:Enkephalin, D-Penicillamine (2,5)-; D000068579:Celecoxib
keywords: CRF; MC4; PGD2; food intake; δ-opioid receptor