Intracellular interplay between cholecystokinin and leptin signalling for satiety control in rats

被引：10

作者：

Koizumi, Hayato ^{[1
,2
]}

Mohammad, Shahid ^{[1
,3
]}

Ozaki, Tomoya ^{[1
,4
]}

Muto, Kiyokazu ^{[2
]}

Matsuba, Nanami ^{[2
]}

Kim, Juhyon ^{[1
,2
]}

Pan, Weihong ^{[5
,6
]}

Morioka, Eri ^{[2
]}

Mochizuki, Takatoshi ^{[2
]}

Ikeda, Masayuki ^{[1
,2
]}

机构：

[1] Univ Toyama, Grad Sch Innovat Life Sci, 3190 Gofuku, Toyama 9308555, Japan

[2] Univ Toyama, Grad Sch Sci & Engn, 3190 Gofuku, Toyama 9308555, Japan

[3] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA

[4] Nagoya Univ, Grad Sch Med, Showa Ku, 65 Tsurumaicho, Nagoya, Aichi 4668550, Japan

[5] Pennington Biomed Res Ctr, Blood Brain Barrier Grp, 6400 Perkins Rd, Baton Rouge, LA 70808 USA

[6] Biopotentials Consulting, Sedona, AZ 86351 USA

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

关键词：

SUPPRESSES FOOD-INTAKE; REDUCING MEAL SIZE; OBESE GENE-PRODUCT; OB PROTEIN; CCK-A; VENTROMEDIAL HYPOTHALAMUS; MESSENGER-RNA; BODY-WEIGHT; RECEPTORS; NEURONS;

D O I：

10.1038/s41598-020-69035-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cholecystokinin (CCK) and leptin are satiety-controlling peptides, yet their interactive roles remain unclear. Here, we addressed this issue using in vitro and in vivo models. In rat C6 glioma cells, leptin pre-treatment enhanced Ca2+ mobilization by a CCK agonist (CCK-8s). This leptin action was reduced by Janus kinase inhibitor (AG490) or PI3-kinase inhibitor (LY294002). Meanwhile, leptin stimulation alone failed to mobilize Ca2+ even in cells overexpressing leptin receptors (C6-ObRb). Leptin increased nuclear immunoreactivity against phosphorylated STAT3 (pSTAT3) whereas CCK-8s reduced leptin-induced nuclear pSTAT3 accumulation in these cells. In the rat ventromedial hypothalamus (VMH), leptin-induced action potential firing was enhanced, whereas nuclear pSTAT3 was reduced by co-stimulation with CCK-8s. To further analyse in vivo signalling interplay, a CCK-1 antagonist (lorglumide) was intraperitoneally injected in rats following 1-h restricted feeding. Food access was increased 3-h after lorglumide injection. At this timepoint, nuclear pSTAT3 was increased whereas c-Fos was decreased in the VMH. Taken together, these results suggest that leptin and CCK receptors may both contribute to short-term satiety, and leptin could positively modulate CCK signalling. Notably, nuclear pSTAT3 levels in this experimental paradigm were negatively correlated with satiety levels, contrary to the generally described transcriptional regulation for long-term satiety via leptin receptors.

引用

页数：15

共 73 条

[71] CHOLECYSTOKININ PERSISTENTLY SUPPRESSES MEAL SIZE BUT NOT FOOD-INTAKE IN FREE-FEEDING RATS [J].