The ontogeny of postingestive inhibitory stimuli: Examining the role of CCK

Weller, Aron

doi:10.1002/dev.20148

Cited by 24 publications

(12 citation statements)

References 59 publications

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“…These data suggest the presence of a satiety deficit even at early ages. Exogenous CCK has the ability to inhibit independent ingestion in newborn rats as early as postnatal day 1 (44) but the role of endogenous CCK in ingestive control has been thought to emerge later in development (45). The results with OLETF rats demonstrating increased intake expressed as prolonged licking as early as postnatal day 2 suggest an earlier role for endogenous CCK in ingestive control.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the obesity of OLETF rats

Moran

2008

Physiology & Behavior

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Cholecystokinin (CCK) is a brain gut peptide that plays an important role in satiety. CCK inhibits food intake by reducing meal size. CCK's satiety actions are mediating through its interaction with CCK1 receptors. Otsuka Long Evans Tokushima Fatty (OLETF) rats are a CCK1 receptor knockout model that allows the study of multiple CCK functions. OLETF rats are hyperphagic with the hyperphagia expressed as a significant increase in the size of meals. OLETF rat obesity is secondary to the hyperphagia and has been propose to derive from two regulatory deficits. One is secondary to the loss of a feedback satiety signal. The other results from increased dorsomedial hypothalamic NPY expression. Recent studies have examined developmental aspects of altered feeding, body weight and orexigenic signaling on OLETF rats. OLETF rats demonstrate increases in meal size in independent ingestion tests as early as two days of age. OLETF pups are also more efficient in suckling situations. Consistent with such developmental differences, examinations of patterns of hypothalamic gene expression in OLETF pups indicate significant increases in DMH NPY expression as early as postnatal Day 15. Access to a running wheel and the resulting exercise have age dependent effects on OLETF food intake and obesity. With running wheel access shortly after weaning, food intake decreases to the levels of LETO controls. When running wheel access is discontinued, food intake temporarily increases resulting in an intermediate phenotype and the absence of diabetes. Together these data demonstrate roles for peripheral CCK and CCK in feeding and body weight control and support the use of the OLETF rat as a model for examining obesity development and for investigating how interventions at critical developmental time points can alter genetic influences on food intake and body weight.

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Section: Discussionmentioning

confidence: 99%

Unraveling the obesity of OLETF rats

Moran

2008

Physiology & Behavior

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“…Specifically, receptor mechanisms in the gut release cholecystokinin in response to protein hydrolysates, 51 which provides a mechanistic pathway for associations among protein hydrolysate ingestion, cholecystokinin release, and satiation. 14,15,[50][51][52][53] In addition, receptor mechanisms for certain amino acids, such as free glutamate, are present in the gut, which, in turn, signal the presence of ingested protein 12 through stimulation of the vagus nerve. 54 The vagus, a principal transmitter of foodrelated messages from the gastrointestinal mucosa to the central nervous system, seems to be the primary pathway that conveys gut glutamate information to the brain as minimal plasma glutamate passes the blood-brain barrier.…”

Section: Figurementioning

confidence: 99%

Differential Growth Patterns Among Healthy Infants Fed Protein Hydrolysate or Cow-Milk Formulas

2011

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WHAT'S KNOWN ON THIS SUBJECT:The different classes of formulas, and different brands within each class, vary in composition and flavor profiles, both of which may influence feeding and growth patterns. Because recent evidence suggests that, relative to intact proteins, hydrolyzed proteins are absorbed and metabolized in a way that promotes greater satiation, we conducted a randomized study on healthy, formula-fed infants to determine whether growth patterns and feeding behaviors differ on the basis of formula type. WHAT THIS STUDY ADDS:Not all formulas are alike. On the basis of World Health Organization standards, z-score trajectories indicate that cow-milk formula-fed infants' weight gain was accelerated, whereas protein-hydrolysate formula-fed infants' weight gain was normative.abstract OBJECTIVE: Infant formulas differ considerably in composition and sensory profiles. In this randomized study, we examined whether healthy infants fed an extensively protein hydrolysate formula (PHF) would differ in feeding behavior and growth from those fed cow-milk formula (CMF). PATIENTS AND METHODS: Infants were randomly assigned to be fed CMF or PHF between 0.5 and 7.5 months of age. Each month for 7 months, infants were weighed and measured and then videotaped while being fed their assigned formula. Anthropometric z scores were calculated by using World Health Organization growth standards. Multilevel linear growth and piecewise mixed-effects models compared trajectories for growth measures and formula acceptance. RESULTS: When compared with infants fed CMF, infants fed PHF had significantly lower weight-for-length z scores across ages 2.5 to 7.5 months. There were no differences in length-for-age z scores, which indicate that group differences resulted from gains in weight, not length. Infants fed PHF also had significantly slower weight gain velocity compared with infants fed CMF. During the monthly assessments, PHF-fed infants consumed less formula to satiation than did CMF-fed infants across the study period. Maternal ratings of infants' acceptance of the formula did not differ at any age. CONCLUSIONS: z-score trajectories indicate that CMF-fed infants' weight gain was accelerated, whereas PHF-fed infants' weight gain was normative. Whether such differences in growth are because of differences in the protein content or amino acid profile of the formulas and, in turn, metabolism is unknown. Research on the long-term consequences of these early growth differences is needed. This trial has been registered at www.clinicaltrials.gov (identifier NCT00994747).

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“…CCK is a brain-gut peptide that acts as a peripheral satiety molecule (Smith, 2006; Weller, 2006) and elicits the earlier appearance of the behavioral satiety sequence (Gibbs et al, 1973), limiting the size of the meals. The absence of this signal causes chronic hyperphagia that eventually induces OLETF males and females to become obese and hyperleptinemic (Moran & Bi, 2006; Schroeder et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of obesity by early-life food restriction in genetically hyperphagic male OLETF rats: Peripheral mechanisms

Schroêder

Moran

Weller

2010

Hormones and Behavior

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The alarming increase in childhood, adolescent and adult obesity has exposed the need for understanding early factors affecting obesity and for treatments that may help prevent or moderate its development. In the present study, we used the OLETF rat model of early-onset hyperphagia induced obesity, which become obese as a result of the absence of CCK1 receptors, to examine the influence of partial food restriction on peripheral adiposity-related parameters during and after chronic and early short term food restriction. Pair feeding (to the amount of food eaten by control, LETO rats) took place from weaning until postnatal day (PND) 45 (early) or from weaning until PND90 (chronic). We examined fat pad weight (brown, retroperitoneal, inguinal & epididymal); inguinal adipocyte size and number; and plasma leptin, oxytocin & creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake after release from food-restriction. The results showed that chronic food restriction produced significant reductions in adiposity parameters, hormones and body weight, while early food restriction successfully reduced long term body weight, intake and adiposity, without affecting plasma measurements. Early (and chronic) dieting produced promising long term effects that may imply the reorganization of both peripheral and central mechanisms that determine energy balance and further support the theory suggesting that early interventions may effectively moderate obesity, even in the presence of a genetic tendency.

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The ontogeny of postingestive inhibitory stimuli: Examining the role of CCK

Cited by 24 publications

References 59 publications

Unraveling the obesity of OLETF rats

Unraveling the obesity of OLETF rats

Differential Growth Patterns Among Healthy Infants Fed Protein Hydrolysate or Cow-Milk Formulas

Attenuation of obesity by early-life food restriction in genetically hyperphagic male OLETF rats: Peripheral mechanisms

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