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Hypothalamic and hindbrain parenchymal studies support a distributed view of melanocortinergic control of energy expenditure and food intake
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T.H. Moran / Appetite 51 (2010) 350–412
Central anorexic action of BDNF in male and female rats H. SHI ∗ , J.G. BARRERA, S.C. WOODS, R.J. SEELEY. University of Cincinnati, Cincinnati, USA Experimental evidence implicates brain-derived neurotrophic factor (BDNF) in the regulation of energy balance. Mice with decreased expression of BDNF, or of its high-affinity receptor TrkB, are hyperphagic and obese; interestingly, this phenotype is more pronounced in females. BDNF and estrogen receptor ␣ are highly expressed and partially co-localized in the ventromedial hypothalamus, raising the possibility that BDNF and estrogen interact to regulate energy balance. Therefore, we hypothesized that sex differences exist in the central anorexic action of BDNF, with females being more sensitive than males. We first determined whether central administration of BDNF produces differential anorexic effects in male vs. cycling female rats. BDNF (0.1, 0.3, and 1.0 g, i3vt) reduced food intake and body weight to the same degree in males and females. We then asked whether estradiol (E2) modulates hypothalamic BDNF expression by comparing BDNF mRNA levels in females across different phases of the estrous cycle as well as in ovariectomized (OVX) females vs. OVX females with E2 replacement. BDNF mRNA levels were similar across the estrous cycle and did not correlate with circulating E2 levels. However, OVX females in which E2 was replaced to supra-physiological levels had significantly more BDNF mRNA than OVX females. In conclusion, central administration of BDNF, at the doses tested, produced comparable anorexic effects in male and female rats. In addition, within the physiological range, E2 did not modify hypothalamic BDNF mRNA levels; however, when replaced at pharmacological doses, E2 significantly increased BDNF mRNA. doi:10.1016/j.appet.2008.04.221
Hypothalamic and hindbrain parenchymal studies support a distributed view of melanocortinergic control of energy expenditure and food intake K.P. SKIBICKA ∗ , H.J. GRILL. UPenn, Phl, USA Human and animal data indicate that central melanocortin (MC) system is crucial role to energy balance (EB). Lateral icv delivery of MCR agonist (MTII) increases energy expenditure (EE) and decreases food intake (FI). As MCRs are anatomically distributed and lateral icv stimulation accesses many brain nuclei, it is unclear which receptor subpopulations mediate MCR effects. On the basis of selective MC4R re-expression, Balthasar et al. (2005) concludes that divergent MC4R populations control EE (hindbrain) and FI (hypothalamus). It is worth noting, however, that MCR nuclei in both hypothalamus and hindbrain contribute to sympathetic outflow. We hypothesized that EE effects of MCR stimulation are obtained by selective stimulation of anatomically distinct CNS nuclei. Here, an icv subthreshold dose of MTII (10 pmol) was applied to sites within hindbrain and hypothalamus; core temperature (Tc ), heart rate (HR), spontaneous activity (SPA) and FI were measured. MTII applied to raphe pallidus or NTS increased Tc , HR, and SPA and decreased FI. RVLM or retrochiasmatic area MTII injection increased Tc , HR and decreased FI. PVN delivery increased HR and SPA, without changes in Tc . Anterior hypothalamic area injection was without effect. Results: (1) highlight MCR expressing nuclei previously unrecognized for their contribution to intake and EE control and (2) demonstrate that while MCR-mediated EB response profiles differ for each nucleus tested, MCR-elicited energetic and anorexic responses are not regionally divergent as they are elicited from multiple, widely distributed MCR populations. Acknowledgment: Supported by DK21397. doi:10.1016/j.appet.2008.04.222
Jejunal pouch reconstruction but not preservation of duodenal passage after total gastrectomy reduces plasma cholecystokinin and pancreatic polypeptide long-term in pigs U. SMEDH 1,∗ , T. ZILLING 2 . 1 Lund University Hospital, Lund, Sweden 2 Varberg County Hospital, Varberg, Sweden Background: The aim of the study was to evaluate the long-term effects of reconstructions of the gastrointestinal tract after gastrectomy, on fasting plasma levels of gastrointestinal hormones known to contribute to food intake controls and satiety. Methods: Domestic Swedish pigs were randomly selected to sham surgery or gastrectomy followed by reconstruction; oesophago-jejunostomy on a Roux-en-Y loop (OJ-RY), jejunal interposition between the oesophagus and the duodenum (OJD), or an oesophago-jejunostomy with a jejunal pouch reservoir (J-pouch) on a Roux-en-Y loop. Blood was collected just before surgery and after 3 months. Plasma levels of peptides were analysed by RIA. Results: Three months after surgery, levels of cholecystokinin and pancreatic polypeptide were significantly lowered (79.6% and 67.0%, respectively) in animals with a jejunal pouch, but not in sham-operated animals or animals with OJ-RY or OD. There were no significant changes in fasting levels of NPY or PYY, irrespective of mode of reconstruction. Conclusion: The present study shows that reconstruction with a jejunal pouch reservoir, but not preservation of duodenal passage, after total gastrectomy significantly lowered levels of CCK and PP, peptides considered to act in the periphery to reduce food intake. doi:10.1016/j.appet.2008.04.223
The acute effects of a lunch containing resistant starch on energy and substrate utilization, ghrelin, GLP-1, PYY concentrations, and satiety A. SMEETS 1,2,∗ , T. GELENCSER 3 , A. SALGO 3 , M. WESTERTERPPLANTENGA 1,2 . 1 Maastricht University, Department of Human Biology, Maastricht, Netherlands 2 Top Institute Food and Nutrition, Wageningen, Netherlands 3 Technical University of Budapest, Department of Biochemistry and Food Technology, Budapest, Hungary Observations of epidemiological studies indicate that dietary fiber intake is involved in body weight control. A dietary fiber component that may be of specific importance is resistant starch (RS). Acute effects of RS on metabolism have hardly been studied and the effects of RS on ghrelin, PYY and GLP-1, in relation to changes in appetite are unknown. Thirty subjects (age: 31 ± 14 year, BMI: 23.8 ± 2.8 kg/m2 ) were studied two times in a crossover design. After 30 min resting on a bed, energy expenditure (EE) was measured and subsequently lunch was served (35% of daily energy requirement, 60% carbohydrates/10% protein/30% fat). The two lunch conditions were: (i) normal pasta and (ii) resistant starch pasta. During 3 h after the lunch diet induced EE was measured. Furthermore, visual analogue scales on the appetite profile were collected before and after lunch, and blood samples were taken for GLP-1, PYY, and ghrelin responses, before and after lunch. Satiety and EE were not different after RS lunch compared with the control lunch. Ghrelin, GLP-1 and PYY responses were not different between the RS lunch and the control lunch. In conclusion, RS supplementation has no acute effect on substrate utilization, appetite feelings, and gut derived hormones. doi:10.1016/j.appet.2008.04.224
T.H. Moran / Appetite 51 (2010) 350–412
Central anorexic action of BDNF in male and female rats H. SHI ∗ , J.G. BARRERA, S.C. WOODS, R.J. SEELEY. University of Cincinnati, Cincinnati, USA Experimental evidence implicates brain-derived neurotrophic factor (BDNF) in the regulation of energy balance. Mice with decreased expression of BDNF, or of its high-affinity receptor TrkB, are hyperphagic and obese; interestingly, this phenotype is more pronounced in females. BDNF and estrogen receptor ␣ are highly expressed and partially co-localized in the ventromedial hypothalamus, raising the possibility that BDNF and estrogen interact to regulate energy balance. Therefore, we hypothesized that sex differences exist in the central anorexic action of BDNF, with females being more sensitive than males. We first determined whether central administration of BDNF produces differential anorexic effects in male vs. cycling female rats. BDNF (0.1, 0.3, and 1.0 g, i3vt) reduced food intake and body weight to the same degree in males and females. We then asked whether estradiol (E2) modulates hypothalamic BDNF expression by comparing BDNF mRNA levels in females across different phases of the estrous cycle as well as in ovariectomized (OVX) females vs. OVX females with E2 replacement. BDNF mRNA levels were similar across the estrous cycle and did not correlate with circulating E2 levels. However, OVX females in which E2 was replaced to supra-physiological levels had significantly more BDNF mRNA than OVX females. In conclusion, central administration of BDNF, at the doses tested, produced comparable anorexic effects in male and female rats. In addition, within the physiological range, E2 did not modify hypothalamic BDNF mRNA levels; however, when replaced at pharmacological doses, E2 significantly increased BDNF mRNA. doi:10.1016/j.appet.2008.04.221
Hypothalamic and hindbrain parenchymal studies support a distributed view of melanocortinergic control of energy expenditure and food intake K.P. SKIBICKA ∗ , H.J. GRILL. UPenn, Phl, USA Human and animal data indicate that central melanocortin (MC) system is crucial role to energy balance (EB). Lateral icv delivery of MCR agonist (MTII) increases energy expenditure (EE) and decreases food intake (FI). As MCRs are anatomically distributed and lateral icv stimulation accesses many brain nuclei, it is unclear which receptor subpopulations mediate MCR effects. On the basis of selective MC4R re-expression, Balthasar et al. (2005) concludes that divergent MC4R populations control EE (hindbrain) and FI (hypothalamus). It is worth noting, however, that MCR nuclei in both hypothalamus and hindbrain contribute to sympathetic outflow. We hypothesized that EE effects of MCR stimulation are obtained by selective stimulation of anatomically distinct CNS nuclei. Here, an icv subthreshold dose of MTII (10 pmol) was applied to sites within hindbrain and hypothalamus; core temperature (Tc ), heart rate (HR), spontaneous activity (SPA) and FI were measured. MTII applied to raphe pallidus or NTS increased Tc , HR, and SPA and decreased FI. RVLM or retrochiasmatic area MTII injection increased Tc , HR and decreased FI. PVN delivery increased HR and SPA, without changes in Tc . Anterior hypothalamic area injection was without effect. Results: (1) highlight MCR expressing nuclei previously unrecognized for their contribution to intake and EE control and (2) demonstrate that while MCR-mediated EB response profiles differ for each nucleus tested, MCR-elicited energetic and anorexic responses are not regionally divergent as they are elicited from multiple, widely distributed MCR populations. Acknowledgment: Supported by DK21397. doi:10.1016/j.appet.2008.04.222
Jejunal pouch reconstruction but not preservation of duodenal passage after total gastrectomy reduces plasma cholecystokinin and pancreatic polypeptide long-term in pigs U. SMEDH 1,∗ , T. ZILLING 2 . 1 Lund University Hospital, Lund, Sweden 2 Varberg County Hospital, Varberg, Sweden Background: The aim of the study was to evaluate the long-term effects of reconstructions of the gastrointestinal tract after gastrectomy, on fasting plasma levels of gastrointestinal hormones known to contribute to food intake controls and satiety. Methods: Domestic Swedish pigs were randomly selected to sham surgery or gastrectomy followed by reconstruction; oesophago-jejunostomy on a Roux-en-Y loop (OJ-RY), jejunal interposition between the oesophagus and the duodenum (OJD), or an oesophago-jejunostomy with a jejunal pouch reservoir (J-pouch) on a Roux-en-Y loop. Blood was collected just before surgery and after 3 months. Plasma levels of peptides were analysed by RIA. Results: Three months after surgery, levels of cholecystokinin and pancreatic polypeptide were significantly lowered (79.6% and 67.0%, respectively) in animals with a jejunal pouch, but not in sham-operated animals or animals with OJ-RY or OD. There were no significant changes in fasting levels of NPY or PYY, irrespective of mode of reconstruction. Conclusion: The present study shows that reconstruction with a jejunal pouch reservoir, but not preservation of duodenal passage, after total gastrectomy significantly lowered levels of CCK and PP, peptides considered to act in the periphery to reduce food intake. doi:10.1016/j.appet.2008.04.223
The acute effects of a lunch containing resistant starch on energy and substrate utilization, ghrelin, GLP-1, PYY concentrations, and satiety A. SMEETS 1,2,∗ , T. GELENCSER 3 , A. SALGO 3 , M. WESTERTERPPLANTENGA 1,2 . 1 Maastricht University, Department of Human Biology, Maastricht, Netherlands 2 Top Institute Food and Nutrition, Wageningen, Netherlands 3 Technical University of Budapest, Department of Biochemistry and Food Technology, Budapest, Hungary Observations of epidemiological studies indicate that dietary fiber intake is involved in body weight control. A dietary fiber component that may be of specific importance is resistant starch (RS). Acute effects of RS on metabolism have hardly been studied and the effects of RS on ghrelin, PYY and GLP-1, in relation to changes in appetite are unknown. Thirty subjects (age: 31 ± 14 year, BMI: 23.8 ± 2.8 kg/m2 ) were studied two times in a crossover design. After 30 min resting on a bed, energy expenditure (EE) was measured and subsequently lunch was served (35% of daily energy requirement, 60% carbohydrates/10% protein/30% fat). The two lunch conditions were: (i) normal pasta and (ii) resistant starch pasta. During 3 h after the lunch diet induced EE was measured. Furthermore, visual analogue scales on the appetite profile were collected before and after lunch, and blood samples were taken for GLP-1, PYY, and ghrelin responses, before and after lunch. Satiety and EE were not different after RS lunch compared with the control lunch. Ghrelin, GLP-1 and PYY responses were not different between the RS lunch and the control lunch. In conclusion, RS supplementation has no acute effect on substrate utilization, appetite feelings, and gut derived hormones. doi:10.1016/j.appet.2008.04.224