Differential Roles for Cholecystokinin A Receptors in Energy Balance in Rats and Mice

Bi, Sheng; Scott, Karen A.; Kopin, Alan S.; Moran, Timothy H.

doi:10.1210/en.2004-0284

Cited by 105 publications

(100 citation statements)

References 50 publications

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“…This compensatory decrease in meal frequency is also observed for peptides that act through the vagus to influence meal size, such as cholecystokinin, which increases meal size and reduces meal frequency. 32 Interestingly, when switched to the HFHS choice diet, HV rats showed less saturated fat intake and more sugar intake compared with the sham rats on an HFHS choice diet. Furthermore, the levels of POMC mRNA were also different between sham and HV rats on an HFHS choice diet.…”

Section: Discussionmentioning

confidence: 96%

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

et al. 2009

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Objectives:The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat high-sugar (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a high-fat (HF) choice diet with access to chow and saturated fat; or to a high-sugar (HS) choice diet with access to chow and a sugar solution. Method: We first studied caloric intake, body weight gain, hormonal alterations and hypothalamic neuropeptide expression when male Wistar rats were subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Next, we studied caloric intake and body weight gain when rats were subjected to the choice diets for 5 weeks. Finally, we measured neuropeptide expression in hepatic vagotomized rats subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Results: In rats on an HF choice diet, plasma leptin concentrations and proopiomelanocortin (POMC) mRNA increased and neuropeptide Y (NPY) mRNA decreased. Rats on an HFHS choice diet showed identical plasma leptin concentrations as rats on an HF choice diet. However, NPY mRNA increased and POMC mRNA decreased. An HS choice diet for 1 week did not alter hypothalamic neuropeptide expression or plasma leptin concentrations. As hormonal changes did not explain the differences in hypothalamic neuropeptide expression between rats on the choice diets, we addressed whether neuronal feedback signals mediated the hypothalamic neuropeptide response. The POMC mRNA response to different diets depended on an intact innervation of liver and upper intestinal tract. Conclusion: Our data suggest that the specific combination of saturated fat and a 30% sugar solution results in hyperphagiainduced obesity and alters hypothalamic neuropeptide expression, and that the response of the melanocortin system is mediated by the hepatic vagus.

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Section: Discussionmentioning

confidence: 96%

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

et al. 2009

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“…OLETF female rats lost fat during the lactation period, from all the three examined tissues. In the middle of the lactation period and during the transition toward weaning (days [15][16][17][18][19][20][21][22], OLETF dams had reduced weight fat tissues that did not differ from those of LETO controls in the same lactation stage. In contrast, 8 weeks PW OLETF dams gained fats, appearing to re-achieve the same amount as observed in NP.…”

Section: Adipose Tissuesmentioning

confidence: 89%

“…OLETF rats do not appear to have a primary deficit involving arcuate nucleus NPY or POMC signaling but rather a primary deficit in DMH hypothalamic NPY signaling, with upregulated levels of DMH NPY that may contribute to their hyperphagia and obesity. [21][22][23] OLETF rats were chosen for this study for several reasons, beyond their CCK-1 receptor mutation (that allows the examination of CCK-1 mediation of adaptation to lactation). The first arises from our prior experience with this model.…”

Section: Introductionmentioning

confidence: 99%

Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

et al. 2008

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Objective: To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage. Design: Strain differences were examined between Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking expression of functional CCK-1 receptors and Long Evans Tokushima Otsuka (LETO) controls, tested as nulliparous dams, at the 7 and 15th lactation day, at weaning (lactation day 22) or 8 weeks postweaning. Measurements: We measured body mass, fat pads (brown, retroperitoneal and inguinal) and inguinal adipocytes. Plasma levels of leptin and oxytocin were determined. Results: Fat depots of LETO female rats were larger during lactation compared to the levels found in postweaning and nulliparous female rats. LETO female rats gained weight and accumulated fat during pregnancy and lactation, returning to their normal fat levels postweaning. In contrast, OLETF female rats presented lower body weight and fat depots during the lactation period than nulliparous dams, and regained the weight and fat postweaning. Plasma leptin and oxytocin were highly correlated and followed the same pattern. OLETF leptin levels were highly correlated with fat depot and inguinal cell surface. No significant correlation was found for LETO parameters. Conclusions: Pregnancy and lactation are energy-consuming events, which naturally induce female rats to increase food intake and accumulate fat. When challenged by the demands of rapidly growing preobese OLETF pups, OLETF dams' fat stores are reduced to lean, LETO levels. During lactation, sensitivity of the oxytocinergic neurons descending from the paraventricular nuclei to the nucleus of the solitary tract to CCK is reduced. We theorized that this pathway is not available to OLETF female rats that lack functional CCK-1 receptors to mediate the signal. The current study contributes to the understanding of the female body's adaptation to lactation.

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“…An abnormality in satiety signaling alone does not necessarily cause obesity (23), unless it affects fundamental homeostatic mechanisms. As leptin is particularly important for long-term metabolic homeostasis, we examined whether leptin administration activates PrRP neurons.…”

Section: Figurementioning

confidence: 99%

Endogenous prolactin-releasing peptide regulates food intake in rodents

Matsumoto²,

et al. 2008

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Food intake is regulated by a network of signals that emanate from the gut and the brainstem. The peripheral satiety signal cholecystokinin is released from the gut following food intake and acts on fibers of the vagus nerve, which project to the brainstem and activate neurons that modulate both gastrointestinal function and appetite. In this study, we found that neurons in the nucleus tractus solitarii of the brainstem that express prolactin-releasing peptide (PrRP) are activated rapidly by food ingestion. To further examine the role of this peptide in the control of food intake and energy metabolism, we generated PrRP-deficient mice and found that they displayed late-onset obesity and adiposity, phenotypes that reflected an increase in meal size, hyperphagia, and attenuated responses to the anorexigenic signals cholecystokinin and leptin. Hypothalamic expression of 6 other appetite-regulating peptides remained unchanged in the PrRP-deficient mice. Blockade of endogenous PrRP signaling in WT rats by central injection of PrRP-specific mAb resulted in an increase in food intake, as reflected by an increase in meal size. These data suggest that PrRP relays satiety signals within the brain and that selective disturbance of this system can result in obesity and associated metabolic disorders.

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Differential Roles for Cholecystokinin A Receptors in Energy Balance in Rats and Mice

Cited by 105 publications

References 50 publications

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia

Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

Endogenous prolactin-releasing peptide regulates food intake in rodents

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