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Xéno-hormone exposure during pregnancy and lactation modify sweet preference of male but not female offspring
T.H. Moran / Appetite 51 (2010) 350–412
Peptide YY: Food for thought R. BATTERHAM . University College London, London, United Kingdom Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour. In response to eating, several hormones are released from the gut which play a role in regulating body weight. Peptide YY (PYY), circulating predominantly as an N-terminally truncated form PYY336, is one such hormone. Exogenous administration of PYY3-36 reduces food intake in obese humans and rodents. Moreover, new lines of evidence support a role for endogenous PYY3-36 in body weight regulation. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. To investigate in humans the brain circuits upon which PYY3-36 acts a double-blind placebo controlled study was undertaken, combining PYY3-36 infusion, continuous functional magnetic resonance imaging and behavioural measures. PYY3-36 modulated neural activity within brainstem and hypothalamic regions consistent with rodent studies. However, the greatest effect of PYY3-36 on brain activity was seen within the left caudolateral orbital frontal cortex (OFC), a polymodal brain region implicated in reward processing. Under high PYY3-36 plasma conditions, mimicking the fed state, changes in neural activity within the OFC predicted subsequent feeding behaviour. In contrast, in low PYY3-36 conditions, hypothalamic activation predicted subsequent food intake. Thus the presence of postprandial plasma concentrations of PYY3-36 switched food intake regulation from a homeostatic to a hedonic, corticolimbic area. doi:10.1016/j.appet.2008.04.033
´ Xeno-hormone exposure during pregnancy and lactation modify sweet preference of male but not female offspring ` S. ISSANCHOU, M.C. CANIVENC-LAVIER. UMR FLAVIC R. BERGES, INRA-Universit´e de Bourgogne, Dijon, France Gonadal hormones have important effects on behaviours that determine body weight in laboratory rats (eating, thermoregulation. . .) and taste preferences. This is most evident in female where consistent changes are correlated with plasma hormone fluctuations during oestrous cycles, puberty and pregnancy, ovariectomy and subsequent estradiol replacement. More, sweet taste sensitivity increased with estradiol levels and estradiol neonatal exposure modifies the sweet preference in offspring. So, owing to these effects, obesity has been proposed to be another adverse health effect of exposure to chemicals with hormone-like activity. Our aim is to identify the effect of a early exposure to dietary xenohormone on the sweet preference of female and male offspring. For that, we selected genistein, a phytoestrogen from food soy, and vinclozolin, an anti-androgen food contaminant used as fungicide. They were given alone or in association to females during pregnancy and lactation at the daily dose of 1mg/kg bw. Sweet taste preference has been established using the two bottle test on the offspring at the weaning age and at the adult age. We found that both, genistein and vinclozolin, enhanced saccharin intake and sweet preference only in male at the weaning but not at the adult age. Our results indicated that early exposure to dietary xeno-hormone at a dose less than NOAEL could modify sweet preference on the offspring in a similar manner than estrogens. These results needed further investigations to correlate this effect with food intake, body weight and adiposity. doi:10.1016/j.appet.2008.04.034
353
Eating for pleasure or calories: Neural integration of cognitive, emotional, and metabolic drives H.-R. BERTHOUD ∗ , H. ZHENG, N.R. LENARD. Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, USA Exposed to palatable and energy dense foods and a sedentary lifestyle, predisposed humans and rodents develop obesity despite homeostatic regulatory mechanisms. An evolutionarily conserved system rigorously defending the lower, but only weakly the upper limits of adiposity appears to be the underlying principle. Powerful hormonal and neural signaling mechanisms have evolved to broadcast nutrient deficiency throughout the body orchestrating optimal responding by preserving existing and procuring new energy sources. Examples include ghrelin secreted from the empty gut and low leptin levels from inadequate fat stores. Both, ghrelin and low leptin stimulate the food-finding processes through their actions on brain systems involved in sensory perception, spatial exploration, learning and memory, reward, and ingestion. While highly responsive to nutrient depletion signals, these functions are relatively resistant to signals reflecting normal or increased levels of adiposity. As a consequence, the “normal” level of activity in cortico-limbic systems of reward responds to the rich food environment to produce hyperphagia and obesity in prone individuals. This conclusion is supported by genetic analyses in humans, showing that most of the predisposing genes primarily affect food intake. The three most promising options to prevent or treat hyperphagia and obesity currently are (1) changes in the food environment, (2) pharmacological tools tweaking critical brain systems, or (3) surgical interventions. Acknowledgments: DK47348 and DK071082. doi:10.1016/j.appet.2008.04.035
Dorsomedial hypothalamic neuropeptide Y modulates the satiety actions of peripheral cholecyctokinin S. BI ∗ , L. YANG, K.A. SCOTT, N. TRAY, T.H. MORAN. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA Previous studies have suggested that dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) may serve as an important signal to regulate energy balance. In this study, we sought to assess a role for DMH NPY in feeding control using adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) for knocking down NPY gene expression in the DMH. We injected AAVshNPY bilaterally into the DMH and examined the feeding effects of knockdown of DMH NPY gene expression in Sprague–Dawley rats. We found that although body weight gain and daily food intake were not significantly affected by AAVshNPY, AAVshNPY rats had altered meal patterns. Meal size was significantly decreased primarily during the dark cycle in AAVshNPY rats. In compensation for this decrease, meal number was increased. We further found that knockdown of DMH NPY gene expression enhanced the feeding response to peripheral administration of cholecyctokinin (CCK). Peripheral CCK administration produced a greater feeding inhibition in AAVshNPY rats relative to rats receiving control vectors (AAVshCTL). Consistent with this feeding effect, c-Fos like immunohistochemistry revealed that peripheral CCK administration increased the number of c-Fos positive cells in the nucleus of the solitary tract at a greater level in AAVshNPY rats as compared with AAVshCTL rats. Together, these results suggest that DMH NPY plays an important role in modulating within meal satiety signaling. Acknowledgment: Supported by NIH DK074269. doi:10.1016/j.appet.2008.04.036
Peptide YY: Food for thought R. BATTERHAM . University College London, London, United Kingdom Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour. In response to eating, several hormones are released from the gut which play a role in regulating body weight. Peptide YY (PYY), circulating predominantly as an N-terminally truncated form PYY336, is one such hormone. Exogenous administration of PYY3-36 reduces food intake in obese humans and rodents. Moreover, new lines of evidence support a role for endogenous PYY3-36 in body weight regulation. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. To investigate in humans the brain circuits upon which PYY3-36 acts a double-blind placebo controlled study was undertaken, combining PYY3-36 infusion, continuous functional magnetic resonance imaging and behavioural measures. PYY3-36 modulated neural activity within brainstem and hypothalamic regions consistent with rodent studies. However, the greatest effect of PYY3-36 on brain activity was seen within the left caudolateral orbital frontal cortex (OFC), a polymodal brain region implicated in reward processing. Under high PYY3-36 plasma conditions, mimicking the fed state, changes in neural activity within the OFC predicted subsequent feeding behaviour. In contrast, in low PYY3-36 conditions, hypothalamic activation predicted subsequent food intake. Thus the presence of postprandial plasma concentrations of PYY3-36 switched food intake regulation from a homeostatic to a hedonic, corticolimbic area. doi:10.1016/j.appet.2008.04.033
´ Xeno-hormone exposure during pregnancy and lactation modify sweet preference of male but not female offspring ` S. ISSANCHOU, M.C. CANIVENC-LAVIER. UMR FLAVIC R. BERGES, INRA-Universit´e de Bourgogne, Dijon, France Gonadal hormones have important effects on behaviours that determine body weight in laboratory rats (eating, thermoregulation. . .) and taste preferences. This is most evident in female where consistent changes are correlated with plasma hormone fluctuations during oestrous cycles, puberty and pregnancy, ovariectomy and subsequent estradiol replacement. More, sweet taste sensitivity increased with estradiol levels and estradiol neonatal exposure modifies the sweet preference in offspring. So, owing to these effects, obesity has been proposed to be another adverse health effect of exposure to chemicals with hormone-like activity. Our aim is to identify the effect of a early exposure to dietary xenohormone on the sweet preference of female and male offspring. For that, we selected genistein, a phytoestrogen from food soy, and vinclozolin, an anti-androgen food contaminant used as fungicide. They were given alone or in association to females during pregnancy and lactation at the daily dose of 1mg/kg bw. Sweet taste preference has been established using the two bottle test on the offspring at the weaning age and at the adult age. We found that both, genistein and vinclozolin, enhanced saccharin intake and sweet preference only in male at the weaning but not at the adult age. Our results indicated that early exposure to dietary xeno-hormone at a dose less than NOAEL could modify sweet preference on the offspring in a similar manner than estrogens. These results needed further investigations to correlate this effect with food intake, body weight and adiposity. doi:10.1016/j.appet.2008.04.034
353
Eating for pleasure or calories: Neural integration of cognitive, emotional, and metabolic drives H.-R. BERTHOUD ∗ , H. ZHENG, N.R. LENARD. Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, USA Exposed to palatable and energy dense foods and a sedentary lifestyle, predisposed humans and rodents develop obesity despite homeostatic regulatory mechanisms. An evolutionarily conserved system rigorously defending the lower, but only weakly the upper limits of adiposity appears to be the underlying principle. Powerful hormonal and neural signaling mechanisms have evolved to broadcast nutrient deficiency throughout the body orchestrating optimal responding by preserving existing and procuring new energy sources. Examples include ghrelin secreted from the empty gut and low leptin levels from inadequate fat stores. Both, ghrelin and low leptin stimulate the food-finding processes through their actions on brain systems involved in sensory perception, spatial exploration, learning and memory, reward, and ingestion. While highly responsive to nutrient depletion signals, these functions are relatively resistant to signals reflecting normal or increased levels of adiposity. As a consequence, the “normal” level of activity in cortico-limbic systems of reward responds to the rich food environment to produce hyperphagia and obesity in prone individuals. This conclusion is supported by genetic analyses in humans, showing that most of the predisposing genes primarily affect food intake. The three most promising options to prevent or treat hyperphagia and obesity currently are (1) changes in the food environment, (2) pharmacological tools tweaking critical brain systems, or (3) surgical interventions. Acknowledgments: DK47348 and DK071082. doi:10.1016/j.appet.2008.04.035
Dorsomedial hypothalamic neuropeptide Y modulates the satiety actions of peripheral cholecyctokinin S. BI ∗ , L. YANG, K.A. SCOTT, N. TRAY, T.H. MORAN. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, USA Previous studies have suggested that dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) may serve as an important signal to regulate energy balance. In this study, we sought to assess a role for DMH NPY in feeding control using adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) for knocking down NPY gene expression in the DMH. We injected AAVshNPY bilaterally into the DMH and examined the feeding effects of knockdown of DMH NPY gene expression in Sprague–Dawley rats. We found that although body weight gain and daily food intake were not significantly affected by AAVshNPY, AAVshNPY rats had altered meal patterns. Meal size was significantly decreased primarily during the dark cycle in AAVshNPY rats. In compensation for this decrease, meal number was increased. We further found that knockdown of DMH NPY gene expression enhanced the feeding response to peripheral administration of cholecyctokinin (CCK). Peripheral CCK administration produced a greater feeding inhibition in AAVshNPY rats relative to rats receiving control vectors (AAVshCTL). Consistent with this feeding effect, c-Fos like immunohistochemistry revealed that peripheral CCK administration increased the number of c-Fos positive cells in the nucleus of the solitary tract at a greater level in AAVshNPY rats as compared with AAVshCTL rats. Together, these results suggest that DMH NPY plays an important role in modulating within meal satiety signaling. Acknowledgment: Supported by NIH DK074269. doi:10.1016/j.appet.2008.04.036