Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin

Peters, James H.; Simasko, Steven M.; Ritter, Robert C.

doi:10.1016/j.physbeh.2006.06.017

Cited by 119 publications

(69 citation statements)

References 44 publications

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“…As such, there are a number of postulated mechanisms for the cooperative actions between CCK and leptin, all of which concern action at the level of the vagal afferents. Thus, CCK and leptin have synergistic effects to increase cytosolic calcium concentrations and activate vagal afferent neurons [2,41], leading to the beneficial effects on the regulation of energy balance [33]. Further to this, there is now evidence that leptin- CCK interactions extend beyond neuronal activation and include changes in gene expression.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

2013

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Aims/hypothesis Cholecystokinin (CCK) and leptin are important hormones with effects on energy balance. The present study assessed the biological effects of (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3, smaller isoforms of CCK and leptin, respectively. Methods The actions and overall therapeutic use of (pGluGln)-CCK-8 and [D-Leu-4]-OB3, alone and in combination, were evaluated in normal and high-fat-fed mice. Results (pGlu-Gln)-CCK-8 had prominent (p<0.01 to p< 0.001), acute feeding-suppressive effects, which were significantly augmented (p<0.05 to p<0.01) by [D-Leu-4]-OB3. In agreement, the acute dose-dependent glucose-lowering and insulinotropic actions of (pGlu-Gln)-CCK-8 were significantly enhanced by concurrent administration of [D-Leu-4]-OB3. Twice daily injection of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in high-fat-fed mice for 18 days decreased body weight (p<0.05 to p<0.001), energy intake (p<0.01), circulating triacylglycerol (p<0.01), nonfasting glucose (p<0.05 to p<0.001) and triacylglycerol deposition in liver and adipose tissue (p<0.001). All treatment regimens improved glucose tolerance (p<0.05 to p<0.001) and insulin sensitivity (p<0.001). Combined treatment with (pGlu-Gln)-CCK-8 and [D-Leu-4]-OB3 resulted in significantly lowered plasma insulin levels, normalisation of circulating LDL-cholesterol and decreased triacylglycerol deposition in muscle. These effects were superior to either treatment regimen alone. There were no changes in overall locomotor activity or respiratory exchange ratio, but treatment with (pGlu-Gln)-CCK-8 significantly reduced (p<0.001) energy expenditure. Conclusions/interpretationThese studies highlight the potential of (pGlu-Gln)-CCK-8 alone and in combination with [D-Leu-4]-OB3 in the treatment of obesity and diabetes.

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Section: Discussionmentioning

confidence: 99%

“…In this context, cholecystokinin (CCK) and leptin are two important peptides with pertinent effects on feeding and body weight control [2]. CCK is secreted from intestinal I cells in response to fatty acids and proteins in the intestinal lumen [3].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

2013

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“…11 Leptin also synergizes with anorexigenic gut peptides glucagon-like peptide-1 and cholecystokinin to coordinate satiety signals at this locus. 14,15 However, it remains unclear whether leptin acts directly through NTS LepRb neurons, or indirectly through inputs from the ARC, or both, to control hindbrain satiety signals. A further understanding of the circuitry of these hindbrain LepRb neurons will be crucial to understand how leptin coordinates actions in the central nervous system with signals from the periphery.…”

Section: Leprb Neuron-containing Loci That Modulate Energy Homeostasismentioning

confidence: 99%

Location, location, location: the CNS sites of leptin action dictate its regulation of homeostatic and hedonic pathways

Leinninger

2009

Int J Obes

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The increasing incidence of obesity and obesity-linked disease presents a serious global health threat. To develop truly effective therapies to modulate food intake and promote weight loss, we must understand the physiological regulators that underlie these processes. One crucial mediator of food intake and energy homeostasis is the adipose-derived hormone, leptin, which acts through neurons expressing the long form of the leptin receptor (LepRb). Although most investigation of leptin action has centered on the large population of LepRb neurons in the arcuate nucleus (ARC), this nucleus does not mediate all aspects of leptin action. Indeed, several hypothalamic and extrahypothalamic loci contain substantial numbers of LepRb neurons, each of which presumably mediates distinct aspects of leptin action, and the collective output of these various LepRb populations produces the totality of leptin function. This review will examine known central nervous system loci that contain LepRb neurons and the potential roles for discrete populations of LepRb neurons in the control of homeostatic and hedonic pathways by leptin. Understanding the unique neuroanatomical and functional roles for each locus of leptin action will be important to identify how specific aspects of food intake contribute to obesity. International Journal of Obesity (2009) 33, S14-S17; doi:10.1038/ijo.2009.66Keywords: leptin; hypothalamus; energy balance; dopamine Leptin signaling is crucial for normal energy homeostasisThe incidence of obesity is increasing rapidly, predisposing millions of individuals to obesity-linked diseases such as type 2 diabetes that result in reduced life expectancy. In addition to the considerable personal toll exacted by obesity and its complications, the ongoing treatment of these conditions throughout a patient's life poses a staggering health care cost. These costs will only become more apparent with the dramatic ongoing rise in juvenile obesity that precipitates earlier onset of complications. Clearly, therapies to prevent weight gain and facilitate weight loss are needed, but our limited understanding of the systems that govern energy homeostasis has hindered the development of truly effective treatments.The discovery of leptin represents an important step in our understanding of how the body regulates food intake and energy homeostasis. Lack of leptin in rodents and humans results in obesity, diminished metabolic rate, hyperphagia and attenuated reproductive function. 1 Loss of the long form of the leptin receptor (LepRb) produces the same phenotype, showing the importance of leptin/ LepRb for normal physiology. 2 Although leptin is produced by adipocytes in approximate proportion to fat stores (that is, the more the adipose content, the more the leptin produced) and released into the circulation, LepRb is expressed, and leptin acts, primarily in the central nervous system on subsets of (primarily hypothalamic) neurons that control processes linked to the intake and expenditure of energy. 3 In aggregate, these clusters of...

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“…It has since been shown to act on many more neurons. Leptin also modulates the sensitivity of taste receptor cells in the oral cavity [3], vagal mechanoreceptors in the gut [4], olfactory detection in the olfactory bulb [5], and visual perception of food [6]. It thus appears that leptin can gate food-related sensory input signals even at early stages of processing.…”

Section: The Multiple Neural Systems Controlling Food Intake and Enermentioning

confidence: 99%

Eating for pleasure or calories

Zheng

Berthoud

2007

Current Opinion in Pharmacology

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A changing environment and lifestyle on the background of evolutionary engraved or perinatally imprinted physiological response patterns is the foremost explanation for the current obesity epidemic. However, it is not clear what the mechanisms are by which the modern environment overrides the physiological controls of appetite and homeostatic body weight regulation. Major advances have been made regarding cross talk between metabolic signals and the cognitive/emotional brain that primarily deals with the environment. On one hand, metabolic signals such as leptin and ghrelin have previously unexpected direct effects on learning and memory, as well as liking and wanting. On the other hand, brain areas involved in reward, cognition, and executive control, can override metabolic regulation by talking to the hypothalamus.

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Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin

Cited by 119 publications

References 44 publications

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Comparison of the metabolic effects of sustained CCK1 receptor activation alone and in combination with upregulated leptin signalling in high-fat-fed mice

Location, location, location: the CNS sites of leptin action dictate its regulation of homeostatic and hedonic pathways

Eating for pleasure or calories

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