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Melanocortin-3 receptors and synchronization of rhythms to meal entrainment
Abstracts / Appetite 54 (2010) 631–683
Expected satiety influences actual satiety J.M. BRUNSTROM ∗ , P.J. ROGERS, J.F. BURN, J.M. COLLINGWOOD, O.M. MAYNARD, S.D. BROWN, N.R. SELL University of Bristol, Bristol, United Kingdom We explored the hypothesis that the satiety that we expect a food to confer can influence the actual satiety that is experienced after it has been consumed. In Experiment 1 we manipulated ‘expected satiety’ by telling participants (N = 32) that a ‘fruit smoothie’ contained either a small or a large amount of fruit. All participants consumed the same smoothie. Nevertheless, those in the ‘large amount’ condition reported significantly lower hunger, 0, 1, 2, and 3 h after meal termination. In Experiment 2 we manipulated information about the volume of soup consumed in a meal. Before lunch, participants were shown either 300 ml or 500 ml of soup. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 participants in each). Covert and independent manipulation of the ‘actual’ and ‘perceived’ soup portion was achieved using a computer-controlled peristaltic pump. Immediately after lunch, self-reported hunger was predicted by the actual and not the perceived amount of soup consumed. However, 2 and 3 h after meal termination this pattern was reversed. Hunger was predicted by the perceived and not the actual amount. Together, these findings confirm a role for ‘expected satiety’ and show how memory for a recent eating episode can affect satiety in the inter-meal interval. This research was supported by a BBSRC-DRINC grant (ref: BB/G005443/1). doi:10.1016/j.appet.2010.04.033
Melanocortin-3 receptors and synchronization of rhythms to meal entrainment A.A. BUTLER The Scripps Research Institute, Jupiter, FL, USA Adaptation to nutrient scarcity involves the expression of behavioral and metabolic programs that maximize survival. This process includes the entrainment of the circadian rhythm to facilitate the anticipation of nutrient availability. Determining exactly how temporal restrictions in nutrient availability force changes in the circadian rhythm and the involvement of the molecular clock is unclear. We entered the field with the simple hypothesis that hypothalamic melanocortin neurons are involved in the entrainment of rhythms to food presentation, and regulate inputs into the “food entrainable oscillator”. The hypothalamic melanocortin system coordinates the homeostatic response to variable calorie intake, integrating signals of metabolic status with outputs affecting ingestive behaviors and metabolism. In this presentation I will summarize results from studies showing that C57BL/6J mice lacking functional melanocortin-3 receptors (Mc3r−/−) are a unique genetic model unable to efficiently express food anticipatory activity (FAA) (J. Neurosci., 2008 28(48), 12946–12955). While ad libitum fed Mc3r−/− mice exhibit modest changes in energy homeostasis, they develop a metabolic phenotype involving mixed insulin resistance and altered substrate preference (FASEB J., 2010, 24(3), 862–872). Collectively, these data suggest that Mc3r regulate both behavioral and metabolic adaptation to temporal restrictions in food availability. This is associated with altered rhythmicity in the expression of clock genes in the brain and liver. However, whether this phenomenon is causative or results from metabolic dysregulation is unclear. doi:10.1016/j.appet.2010.04.034
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Hypothalamic neuron derived neurotrophic factor (NENF) regulates food intake M.S. BYERLY 1,∗ , S. AJA 2 , T.H. MORAN 2 , S. BLACKSHAW 1 1 Dept of Neurosci, Johns Hopkins School of Medicine, Baltimore, MD, USA 2 Dept of Psych, Johns Hopkins School of Medicine, Baltimore, MD, USA Identification of novel hypothalamic-expressed secreted factors may help identify novel drug targets for treatment of obesity and eating disorders. We developed a screen to identify novel candidate hypothalamic secreted proteins meeting the following criteria: (1) expression in hypothalamic nuclei known to regulate body composition, hunger or satiety, (2) residing in a genomic locus containing a QTL that regulates body composition or food intake, (3) possessing a signal peptide sequence, (4) showing altered gene expression under fed, fasted and DIO conditions and (5) no prior implication for these processes. Recombinant proteins were generated, injected into the lateral ventricle (LV) and body weight and food intake measurements taken. We characterized one candidate protein further, NENF. A single NENF LV injection (30 nm) once per week partially reversed a chow-induced obese phenotype by decreasing food intake, but this was not observed with obesity induced by a high-fat (HF) diet. The NENF protein injection altered hypothalamic gene expression patterns in a direction that resembled DIO animals. This suggests that the NENF protein may be effective to alleviate obesity induced by a chow diet, but not on a HF diet. Finally, these results demonstrate that we have successfully initiated a screen to identify novel hypothalamic secreted neuropeptides that regulate food intake and body weight. doi:10.1016/j.appet.2010.04.035
Effect of chronic variable stress on central regulation of food intake and neurogenesis J. CALVEZ 1,2,∗ , G. FROMENTIN 1 , N. NADKARNI 1 , N. DARCEL 1 , D. 1 AgroParisTech-INRA, TOMé 1 , N. BALLET 2 , C. CHAUMONTET 1 UMR914 Nutrition Physiology and Ingestive Behavior, Paris, France 2 Lesaffre Feed Additives, Marquette-lez-Lille, France Chronic stress alters several central mechanisms including those of food intake regulation and neurogenesis. Our goal was to determine the effect of chronic variable stress (CVS) on these two systems. Two experiments were performed using 2 weeks CVS in male Wistar rats. CVS consisted of daily unpredictable exposure to a variety of stressors. In the first experiment, food intake and body weight were measured daily. At the end of CVS, hypothalamic neuropeptide mRNA expression, basal plasma hormone levels and body composition were measured. In the second experiment, the effects of CVS on brain morphology were assessed by MRI, and at the cellular level by staining. Rats exposed to CVS displayed greater corticotropin releasing factor (CRF) and a tendency towards lower neuropeptide Y (NPY) expression, plus a decreased body weight due to diminution of adipose tissue mass compared to control rats. A decrease in food intake only partly explained this decrease since stressed rats also showed a reduced weight gain per kJ ingested. Stressed rats had a 2-fold increase in basal corticosterone levels. The effects of CVS on neuroanatomy of the brain are currently being analysed. In conclusion, CVS affected central food intake regulation. CVS induced a decrease in food intake, probably due to CRF inhibition of orexigenic NPY neurons. The lowered body weight of stressed rats could be explained by an inhibition of food intake and, since CVS only lasted 2 weeks, an acute lipolytic effect of corticosterone. doi:10.1016/j.appet.2010.04.036
Expected satiety influences actual satiety J.M. BRUNSTROM ∗ , P.J. ROGERS, J.F. BURN, J.M. COLLINGWOOD, O.M. MAYNARD, S.D. BROWN, N.R. SELL University of Bristol, Bristol, United Kingdom We explored the hypothesis that the satiety that we expect a food to confer can influence the actual satiety that is experienced after it has been consumed. In Experiment 1 we manipulated ‘expected satiety’ by telling participants (N = 32) that a ‘fruit smoothie’ contained either a small or a large amount of fruit. All participants consumed the same smoothie. Nevertheless, those in the ‘large amount’ condition reported significantly lower hunger, 0, 1, 2, and 3 h after meal termination. In Experiment 2 we manipulated information about the volume of soup consumed in a meal. Before lunch, participants were shown either 300 ml or 500 ml of soup. Orthogonal to this, half consumed 300 ml and half consumed 500 ml. This process yielded four separate groups (25 participants in each). Covert and independent manipulation of the ‘actual’ and ‘perceived’ soup portion was achieved using a computer-controlled peristaltic pump. Immediately after lunch, self-reported hunger was predicted by the actual and not the perceived amount of soup consumed. However, 2 and 3 h after meal termination this pattern was reversed. Hunger was predicted by the perceived and not the actual amount. Together, these findings confirm a role for ‘expected satiety’ and show how memory for a recent eating episode can affect satiety in the inter-meal interval. This research was supported by a BBSRC-DRINC grant (ref: BB/G005443/1). doi:10.1016/j.appet.2010.04.033
Melanocortin-3 receptors and synchronization of rhythms to meal entrainment A.A. BUTLER The Scripps Research Institute, Jupiter, FL, USA Adaptation to nutrient scarcity involves the expression of behavioral and metabolic programs that maximize survival. This process includes the entrainment of the circadian rhythm to facilitate the anticipation of nutrient availability. Determining exactly how temporal restrictions in nutrient availability force changes in the circadian rhythm and the involvement of the molecular clock is unclear. We entered the field with the simple hypothesis that hypothalamic melanocortin neurons are involved in the entrainment of rhythms to food presentation, and regulate inputs into the “food entrainable oscillator”. The hypothalamic melanocortin system coordinates the homeostatic response to variable calorie intake, integrating signals of metabolic status with outputs affecting ingestive behaviors and metabolism. In this presentation I will summarize results from studies showing that C57BL/6J mice lacking functional melanocortin-3 receptors (Mc3r−/−) are a unique genetic model unable to efficiently express food anticipatory activity (FAA) (J. Neurosci., 2008 28(48), 12946–12955). While ad libitum fed Mc3r−/− mice exhibit modest changes in energy homeostasis, they develop a metabolic phenotype involving mixed insulin resistance and altered substrate preference (FASEB J., 2010, 24(3), 862–872). Collectively, these data suggest that Mc3r regulate both behavioral and metabolic adaptation to temporal restrictions in food availability. This is associated with altered rhythmicity in the expression of clock genes in the brain and liver. However, whether this phenomenon is causative or results from metabolic dysregulation is unclear. doi:10.1016/j.appet.2010.04.034
637
Hypothalamic neuron derived neurotrophic factor (NENF) regulates food intake M.S. BYERLY 1,∗ , S. AJA 2 , T.H. MORAN 2 , S. BLACKSHAW 1 1 Dept of Neurosci, Johns Hopkins School of Medicine, Baltimore, MD, USA 2 Dept of Psych, Johns Hopkins School of Medicine, Baltimore, MD, USA Identification of novel hypothalamic-expressed secreted factors may help identify novel drug targets for treatment of obesity and eating disorders. We developed a screen to identify novel candidate hypothalamic secreted proteins meeting the following criteria: (1) expression in hypothalamic nuclei known to regulate body composition, hunger or satiety, (2) residing in a genomic locus containing a QTL that regulates body composition or food intake, (3) possessing a signal peptide sequence, (4) showing altered gene expression under fed, fasted and DIO conditions and (5) no prior implication for these processes. Recombinant proteins were generated, injected into the lateral ventricle (LV) and body weight and food intake measurements taken. We characterized one candidate protein further, NENF. A single NENF LV injection (30 nm) once per week partially reversed a chow-induced obese phenotype by decreasing food intake, but this was not observed with obesity induced by a high-fat (HF) diet. The NENF protein injection altered hypothalamic gene expression patterns in a direction that resembled DIO animals. This suggests that the NENF protein may be effective to alleviate obesity induced by a chow diet, but not on a HF diet. Finally, these results demonstrate that we have successfully initiated a screen to identify novel hypothalamic secreted neuropeptides that regulate food intake and body weight. doi:10.1016/j.appet.2010.04.035
Effect of chronic variable stress on central regulation of food intake and neurogenesis J. CALVEZ 1,2,∗ , G. FROMENTIN 1 , N. NADKARNI 1 , N. DARCEL 1 , D. 1 AgroParisTech-INRA, TOMé 1 , N. BALLET 2 , C. CHAUMONTET 1 UMR914 Nutrition Physiology and Ingestive Behavior, Paris, France 2 Lesaffre Feed Additives, Marquette-lez-Lille, France Chronic stress alters several central mechanisms including those of food intake regulation and neurogenesis. Our goal was to determine the effect of chronic variable stress (CVS) on these two systems. Two experiments were performed using 2 weeks CVS in male Wistar rats. CVS consisted of daily unpredictable exposure to a variety of stressors. In the first experiment, food intake and body weight were measured daily. At the end of CVS, hypothalamic neuropeptide mRNA expression, basal plasma hormone levels and body composition were measured. In the second experiment, the effects of CVS on brain morphology were assessed by MRI, and at the cellular level by staining. Rats exposed to CVS displayed greater corticotropin releasing factor (CRF) and a tendency towards lower neuropeptide Y (NPY) expression, plus a decreased body weight due to diminution of adipose tissue mass compared to control rats. A decrease in food intake only partly explained this decrease since stressed rats also showed a reduced weight gain per kJ ingested. Stressed rats had a 2-fold increase in basal corticosterone levels. The effects of CVS on neuroanatomy of the brain are currently being analysed. In conclusion, CVS affected central food intake regulation. CVS induced a decrease in food intake, probably due to CRF inhibition of orexigenic NPY neurons. The lowered body weight of stressed rats could be explained by an inhibition of food intake and, since CVS only lasted 2 weeks, an acute lipolytic effect of corticosterone. doi:10.1016/j.appet.2010.04.036