Cholecystokinin receptors and vagal nerves in control of food intake in rats

Garlicki, J.; Konturek, P C; Majka, Jolanta; Kwiecień, N; Konturek, Stanisław J.

doi:10.1152/ajpendo.1990.258.1.e40

Cited by 35 publications

(27 citation statements)

References 10 publications

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“…We showed that 1 and 10 nmol/kg CCK significantly reduced food intake in naive rats 0.5, 1, and 2 h after ip injection, whereas 0.1 nmol/kg CCK administered ip did not decrease food intake. Consistent with our findings, some studies have shown that the threshold dose of CCK for reduction of food intake in rats is 1 nmol/kg (17,18). Interaction between leptin and CCK reduces short-term food intake (3,39,56).…”

Section: Discussionsupporting

confidence: 92%

Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

Akieda-Asai

Poleni

Date

2014

American Journal of Physiology-Endocrinology and Metabolism

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Akieda-Asai S, Poleni PE, Date Y. Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus. Am J Physiol Endocrinol Metab 306: E1284 -E1291, 2014. First published April 8, 2014 doi:10.1152/ajpendo.00664.2013.-CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine-and amphetamineregulated transcript (CART) and thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance. cholecystokinin; food intake; leptin; midbrain transection FOOD INTAKE IS FINELY REGULATED by a complicated interaction of many orexigenic and anorectic signals produced in the brain and peripheral tissues. To maintain energy balance, information on the metabolic state resulting from feeding-related factors must be transported efficiently to the brain. Leptin, an anorectic hormone produced by white adipose tissue, plays an important role in maintaining energy balance (47). Absence of leptin results in severe obesity in both rodents and humans (13,38). Leptin directly binds to its ObRb receptors, which are located mainly in the hypothalamus and hindbrain; it promotes energy expenditure by stimulating the Janus-activated kinase (JAK)-STAT3 signaling pathway (4). Leptin also inhibits AMP-activated protein kinase (AMPK) activity in the arcuate nucleus and paraventricular nucleus of the hypothalamus (33). Moreover, leptin administration enhances the anorectic response to satiety-signaling molecules such as bombesin (26) or amylin (52).CCK is a gastrointestinal hormone produced by I cells of the proximal small intestine ...

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Section: Discussionsupporting

confidence: 92%

Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

Akieda-Asai

Poleni

Date

2014

American Journal of Physiology-Endocrinology and Metabolism

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“…The time needed to inject rats was ϳ30 s/rat. The dose of CCK was based on previous studies showing a robust reduction of food intake following injection of 2 nmol/kg CCK-8 (17,56). Experiments were repeated in a crossover design in the same batch of rats for each treatment.…”

Section: Methodsmentioning

confidence: 99%

CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

Goebel-Stengel

Stengel²,

Wang³

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…To assess the completeness of the vagotomy, a food intake analysis was performed based on the satiety effect of cholecystokinin-octapeptide (CCK-8) (Sigma Aldrich, St. Louis, MO), which is known to be mediated by the afferent vagus nerve (7,14). All animals were food deprived for 20 h and then received an injection (ip) of 8 g CCK ⅐ kg Ϫ1 ⅐ mouse Ϫ1 , and their 2-h food intake was measured.…”

Section: Methodsmentioning

confidence: 99%

Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

Kleij¹,

O’Mahony²,

Shanahan³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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CD62Lϩ T lymphocytes from BALB/c into SCID mice. LR and BI (1 ϫ 10 9 ) were given daily. Clinical score, myeloperoxidase (MPO) levels, and in vivo and in vitro secreted inflammatory cytokine levels were found to be more severe in mice that were vagotomized compared with shamoperated animals. LR in the acute DSS model was effective in decreasing the MPO and cytokine levels in the tissue in sham and vagotomized mice. BI had a strong downregulatory effect on secreted in vitro cytokine levels and had a greater anti-inflammatory effect in vagotomized-compared with sham-operated mice. Both LR and BI retained anti-inflammatory effects in vagotomized mice. In SCID mice, vagotomy did not enhance inflammation, but BI was more effective in vagotomized mice than shams. Taken together, the intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis. Furthermore, LR and BI do not seem to engage their protective effects via this cholinergic anti-inflammatory pathway, but the results interestingly show that, in the T cell, transfer model vagotomy had a biological effect, since it increased the effectiveness of the BI in downregulation of colonic inflammation.

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Cholecystokinin receptors and vagal nerves in control of food intake in rats

Cited by 35 publications

References 10 publications

Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

Coinjection of CCK and leptin reduces food intake via increased CART/TRH and reduced AMPK phosphorylation in the hypothalamus

CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

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