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Nitric oxide contributes to LPS-induced anorexia
Abstracts / Appetite 54 (2010) 631–683
Gestational stress and high-fat diet effects on maternal behavior, milk composition, pup ingestive behavior and hypothalamic gene expression R.H. PURCELL ∗ , B. SUN, L. PASS, T.H. MORAN, K.L.K. TAMASHIRO Dept. of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA Offspring of prenatally stressed or high-fat diet fed dams have increased body weight and adiposity and are predisposed to dietinduced obesity in adulthood. In this study we characterized the effects of these treatments on maternal behavior, milk composition, pups independent ingestion and hypothalamic neuropeptide expression. Pregnant female rats fed standard chow or high-fat (60%) diet were subjected to a variable stress paradigm in the 3rd week of gestation (CH-STRESS, HF-Stress) or left undisturbed (CH-CON, HF-CON). STRESS dams show less maternal licking and grooming during postnatal week 1 while HF dams show increased arched-back nursing and licking and grooming in week 2. Milk from HF-fed dams had greater fat content than that of CH-fed dams at PND 21. Offspring of both CH-STRESS and HF-STRESS dams had increased milk uptake in an independent ingestion test at PND 3 but showed no difference by PND 10. Pups from HF-fed dams have increased PVN CRH and decreased arcuate NPY expression at PND 21. Pups from STRESS dams had decreased DMH NPY expression on PND 21. Taken together these data suggest that maternal diet and stress alters maternal behavior, and offspring neuropeptide expression in ways that may contribute to increased susceptibility to diet-induced obesity in offspring. Supported by NIH Grants HD055030, DK077623. doi:10.1016/j.appet.2010.04.168
671
Nitric oxide contributes to LPS-induced anorexia T. RIEDIGER ∗ , C. CORDANI, T.A. LUTZ Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland Nitric oxide (NO) is a pro-inflammatory neuromodulator which is produced in the arcuate nucleus (ARC) by inducible nitric oxide synthase (iNOS) in response to the endotoxin lipopolysaccharide (LPS). NO inhibits ghrelin-excited ARC neurons pointing to a possible involvement of NO in disease-related anorexia. We therefore evaluated whether the specific iNOS inhibitor 1400W counteracts the anorectic effect of LPS in rats. In addition we investigated whether LPS-induced anorexia is associated with STAT3 phosphorylation in the ARC. In part of the rats, LPS tolerance was induced by repeated LPS treatment. Rats that received a peripheral 1400W injection (10 mg/kg sc) showed a lower LPS-mediated suppression of food intake than untreated controls. 1400W treatment also attenuated LPS-induced adipsia and it increased physical activity. LPS-induced anorexia was paralleled by a STAT3 phosphorylation in the ARC starting 2–4 h after LPS treatment. LPS did not suppress feeding in rats that were repeatedly (3×) injected with LPS. The loss of LPS-induced anorexia was associated with a blunted pSTAT3 response in the ARC in these rats. This study provides evidence that NO contributes to disease-related anorexia and associated sickness symptoms. A pharmacological blockade of NO formation might be a therapeutically useful approach to prevent disease-related anorexia. STAT signalling might be part of in the pro-inflammatory cascade suppressing food intake. Although STAT is involved in the transcriptional regulation of iNOS expression, the functional link between pSTAT3/NO formation in the ARC and the inhibition of feeding remains to be confirmed. doi:10.1016/j.appet.2010.04.170
Effects of glycine-extended and serine13 -phosphorylated forms of peptide YY on food intake in rats R. REIDELBERGER 1,2,∗ , A. HAVER 2 1 Creighton Unversity, Omaha, NE, USA 2 Omaha VA Medical Center, Omaha, NE, USA
Examining food memories. Relationships between experienced and remembered enjoyment E. ROBINSON ∗ , S. HIGGS, J. BLISSETT University of Birmingham, Birmingham, United Kingdom
Peptide YY (3-36) [PYY(3-36)] is significantly more potent than PYY(1-36) in decreasing food intake in rats and humans. Other Glycine-extended and Ser13 -phosphorylated PYY forms have been detected or predicted based upon known cellular processes of PYY synthesis and modification. We previously showed that 3-h IV infusion of PYY(3-36) at dark onset decreased feeding in rats with free access to food with an estimated mean effective dose of 15 pmol/kg/min, while PYY(1-36) was an order of magnitude less potent than PYY(3-36). Here we compared the effects of 3-h IV infusions of PYY(1-36), PYY(3-36), PYY(136)-Gly, PYY(3-36)-Gly, Ser13 PO3 -PYY(1-36), Ser13 PO3 -PYY(3-36), Ser13 PO3 -PYY(1-36)-Gly, and Ser13 PO3 -PYY(3-36)-Gly on food intake in rats under the same experimental conditions. PYY(336) and Ser13 PO3 -PYY(3-36) similarly inhibited food intake at 50 pmol/kg/min, while PYY(3-36), but not Ser13 PO3 -PYY(3-36), inhibited food intake at 15 pmol/kg/min. PYY(1-36)-Gly, PYY(336)-Gly, Ser13 PO3 -PYY(3-36)-Gly, and Ser13 PO3 -PYY(1-36)-Gly had no effect on food intake at doses of 50 or 150 pmol/kg/min. Taken together, these results indicate that (i) PYY(3-36) is an order of magnitude more potent than PYY(1-36), (ii) Gly-extended forms of PYY are significantly less potent than non-extended forms, and (iii) Ser13 -phosphorylation of PYY(3-36) decreases its anorexigenic potency. Thus, PYY(3-36) appears to be the most potent PYY form for reducing food intake in rats. Supported by NIH DK073152 and Medical Research Service of Department of Veterans Affairs. doi:10.1016/j.appet.2010.04.169
Food choice is often dependent on remembered enjoyment of food so there is a need to examine how we construct memories of past eating experiences. Previous research has suggested that the peak, trough, beginning and end of an experience may be important in shaping affective memory. The present study examined the relationship between online rated experience and remembered enjoyment of a meal. Forty participants (26 female, 14 male; 18–33 years old) ate a standardised 5-item lunch. Piloting ensured the amount of time taken to eat each food item was similar across the 5 items. Each participant ate the foods in the same order and after eating a food item (Quiche, carrot sticks, potato chips, pastry and pretzels) they rated how enjoyable the item was (online measure of enjoyment). Participants returned 2 h later and rated their overall enjoyment of the meal. Averaged online rating for the 5 items, the rating of the last item, first item, trough (lowest item rating) and peak (highest item rating) were entered into regression analysis as potential predictors of remembered meal enjoyment. Analysis revealed that participant’s rating of the most enjoyable food item (peak) was the only significant predictor of overall remembered enjoyment. Including the 4 additional predictors in the regression model resulted in no significant increase in explained variance. These data suggest that remembered enjoyment of a multi-item meal is largely dependent on experienced enjoyment during the best part of the meal. Hence meals that contain at least one highly liked item are likely to be remembered positively. doi:10.1016/j.appet.2010.04.171
Gestational stress and high-fat diet effects on maternal behavior, milk composition, pup ingestive behavior and hypothalamic gene expression R.H. PURCELL ∗ , B. SUN, L. PASS, T.H. MORAN, K.L.K. TAMASHIRO Dept. of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA Offspring of prenatally stressed or high-fat diet fed dams have increased body weight and adiposity and are predisposed to dietinduced obesity in adulthood. In this study we characterized the effects of these treatments on maternal behavior, milk composition, pups independent ingestion and hypothalamic neuropeptide expression. Pregnant female rats fed standard chow or high-fat (60%) diet were subjected to a variable stress paradigm in the 3rd week of gestation (CH-STRESS, HF-Stress) or left undisturbed (CH-CON, HF-CON). STRESS dams show less maternal licking and grooming during postnatal week 1 while HF dams show increased arched-back nursing and licking and grooming in week 2. Milk from HF-fed dams had greater fat content than that of CH-fed dams at PND 21. Offspring of both CH-STRESS and HF-STRESS dams had increased milk uptake in an independent ingestion test at PND 3 but showed no difference by PND 10. Pups from HF-fed dams have increased PVN CRH and decreased arcuate NPY expression at PND 21. Pups from STRESS dams had decreased DMH NPY expression on PND 21. Taken together these data suggest that maternal diet and stress alters maternal behavior, and offspring neuropeptide expression in ways that may contribute to increased susceptibility to diet-induced obesity in offspring. Supported by NIH Grants HD055030, DK077623. doi:10.1016/j.appet.2010.04.168
671
Nitric oxide contributes to LPS-induced anorexia T. RIEDIGER ∗ , C. CORDANI, T.A. LUTZ Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland Nitric oxide (NO) is a pro-inflammatory neuromodulator which is produced in the arcuate nucleus (ARC) by inducible nitric oxide synthase (iNOS) in response to the endotoxin lipopolysaccharide (LPS). NO inhibits ghrelin-excited ARC neurons pointing to a possible involvement of NO in disease-related anorexia. We therefore evaluated whether the specific iNOS inhibitor 1400W counteracts the anorectic effect of LPS in rats. In addition we investigated whether LPS-induced anorexia is associated with STAT3 phosphorylation in the ARC. In part of the rats, LPS tolerance was induced by repeated LPS treatment. Rats that received a peripheral 1400W injection (10 mg/kg sc) showed a lower LPS-mediated suppression of food intake than untreated controls. 1400W treatment also attenuated LPS-induced adipsia and it increased physical activity. LPS-induced anorexia was paralleled by a STAT3 phosphorylation in the ARC starting 2–4 h after LPS treatment. LPS did not suppress feeding in rats that were repeatedly (3×) injected with LPS. The loss of LPS-induced anorexia was associated with a blunted pSTAT3 response in the ARC in these rats. This study provides evidence that NO contributes to disease-related anorexia and associated sickness symptoms. A pharmacological blockade of NO formation might be a therapeutically useful approach to prevent disease-related anorexia. STAT signalling might be part of in the pro-inflammatory cascade suppressing food intake. Although STAT is involved in the transcriptional regulation of iNOS expression, the functional link between pSTAT3/NO formation in the ARC and the inhibition of feeding remains to be confirmed. doi:10.1016/j.appet.2010.04.170
Effects of glycine-extended and serine13 -phosphorylated forms of peptide YY on food intake in rats R. REIDELBERGER 1,2,∗ , A. HAVER 2 1 Creighton Unversity, Omaha, NE, USA 2 Omaha VA Medical Center, Omaha, NE, USA
Examining food memories. Relationships between experienced and remembered enjoyment E. ROBINSON ∗ , S. HIGGS, J. BLISSETT University of Birmingham, Birmingham, United Kingdom
Peptide YY (3-36) [PYY(3-36)] is significantly more potent than PYY(1-36) in decreasing food intake in rats and humans. Other Glycine-extended and Ser13 -phosphorylated PYY forms have been detected or predicted based upon known cellular processes of PYY synthesis and modification. We previously showed that 3-h IV infusion of PYY(3-36) at dark onset decreased feeding in rats with free access to food with an estimated mean effective dose of 15 pmol/kg/min, while PYY(1-36) was an order of magnitude less potent than PYY(3-36). Here we compared the effects of 3-h IV infusions of PYY(1-36), PYY(3-36), PYY(136)-Gly, PYY(3-36)-Gly, Ser13 PO3 -PYY(1-36), Ser13 PO3 -PYY(3-36), Ser13 PO3 -PYY(1-36)-Gly, and Ser13 PO3 -PYY(3-36)-Gly on food intake in rats under the same experimental conditions. PYY(336) and Ser13 PO3 -PYY(3-36) similarly inhibited food intake at 50 pmol/kg/min, while PYY(3-36), but not Ser13 PO3 -PYY(3-36), inhibited food intake at 15 pmol/kg/min. PYY(1-36)-Gly, PYY(336)-Gly, Ser13 PO3 -PYY(3-36)-Gly, and Ser13 PO3 -PYY(1-36)-Gly had no effect on food intake at doses of 50 or 150 pmol/kg/min. Taken together, these results indicate that (i) PYY(3-36) is an order of magnitude more potent than PYY(1-36), (ii) Gly-extended forms of PYY are significantly less potent than non-extended forms, and (iii) Ser13 -phosphorylation of PYY(3-36) decreases its anorexigenic potency. Thus, PYY(3-36) appears to be the most potent PYY form for reducing food intake in rats. Supported by NIH DK073152 and Medical Research Service of Department of Veterans Affairs. doi:10.1016/j.appet.2010.04.169
Food choice is often dependent on remembered enjoyment of food so there is a need to examine how we construct memories of past eating experiences. Previous research has suggested that the peak, trough, beginning and end of an experience may be important in shaping affective memory. The present study examined the relationship between online rated experience and remembered enjoyment of a meal. Forty participants (26 female, 14 male; 18–33 years old) ate a standardised 5-item lunch. Piloting ensured the amount of time taken to eat each food item was similar across the 5 items. Each participant ate the foods in the same order and after eating a food item (Quiche, carrot sticks, potato chips, pastry and pretzels) they rated how enjoyable the item was (online measure of enjoyment). Participants returned 2 h later and rated their overall enjoyment of the meal. Averaged online rating for the 5 items, the rating of the last item, first item, trough (lowest item rating) and peak (highest item rating) were entered into regression analysis as potential predictors of remembered meal enjoyment. Analysis revealed that participant’s rating of the most enjoyable food item (peak) was the only significant predictor of overall remembered enjoyment. Including the 4 additional predictors in the regression model resulted in no significant increase in explained variance. These data suggest that remembered enjoyment of a multi-item meal is largely dependent on experienced enjoyment during the best part of the meal. Hence meals that contain at least one highly liked item are likely to be remembered positively. doi:10.1016/j.appet.2010.04.171