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Effects of prenatal diet on food preference and ethanol intake in offspring
Abstracts / Appetite 57S (2011) S1–S49
Viral-mediated overexpression of NPY in the dorsomedial hypothalamus causes hyperphagia and obesity in Sprague Dawley rats S. BI 1 , K.A. SCOTT 1,2 , P.T. CHAO 1 , Y.J. KIM 1 , C. DE LA SERRE 1 , T.H. MORAN 1 1 Johns Hopkins University School of Medicine, Baltimore, USA 2 University of Cincinnati, Cincinnati, USA Previous reports have shown NPY overexpression in the dorsomedial hypothalamus (DMH) in a number of obesity models of rodents. Whether this overexpression plays a causative role in these animal models is not established. To this end, we generated a recombinant vector of adeno-associated virus (AAV)-mediated expression of NPY (AAVNPY) and determined the effect of DMH NPY overexpression on energy homeostasis in adult Sprague Dawley rats. Animals received DMH injections of AAVNPY and food intake and body weight were monitored for 16 weeks. We found that food intake and body weight were significantly increased in NPY overexpression rats compared to rats receiving GFP control vectors. Meal pattern analysis revealed that DMH NPY overexpression specifically increased meal size during the dark period, leading to hyperphagia. NPY overexpression significantly increased fat mass as determined in the areas of inguinal subcutaneous and epididymal white fat and interscapular brown fat. Moreover, while high fat diet access induced obesity in control rats, DMH NPY overexpression exacerbated diet-induced increases in food intake and body weight and resulted in even greater increases in inguinal fat. This overexpression also caused increases in plasma leptin and insulin levels. Together, our results demonstrate that DMH NPY overexpression can result in obesity and implicates this overexpression as causal in a number of obesity models. Supported by: NIH R01DK074269 (to S.B.). doi:10.1016/j.appet.2011.05.124 Inhibitory effects of insulin in the dorsal motor nucleus of the vagus C.B. BLAKE, B.N. SMITH Department of Physiology, College of Medicine, University of Kentucky, Lexington, USA Insulin, which is critical to glucose regulation in the body, crosses the blood brain barrier and is transported into the brainstem over twice as rapidly as into whole brain and may affect glucose regulation via central mechanisms. Brainstem nuclei, specifically the dorsal motor nucleus of the vagus (DMV), are essential for visceral parasympathetic function. Pathologies in which insulin is dysregulated, including diabetes, can disrupt this circuit, leading to gastric and other autonomic dysfunction. Insulin receptors (IRs) are expressed in the DMV, and preliminary data indicates that IRs are located in proximity to gastric-projecting DMV cells. We used whole-cell patch-clamp recordings in brainstem slices to identify effects of insulin on synaptic input to DMV neurons. Insulin significantly reduced the frequency of action potential firing (APs), spontaneous excitatory post-synaptic currents (sEPSCs), and miniature EPSCs, with no change in amplitude. Insulin also reduced sEPSC and AP frequency in a subset of identified gastricrelated DMV neurons. Insulin activity was dependent on the KATP channel and PI3-kinase activity, because the effects of insulin on sEPSC frequency were eliminated in the presence of a KATP channel antagonist, tolbutamide or the PI3-kinase inhibitor, wortmannin. These results suggest that insulin inhibits excitatory input to DMV neurons via a KATP channel- and PI3-kinase-dependent mechanism. Such regulation may influence glucose metabolism in the DMV and thus, autonomic visceral regulation. Supported by: R01 DK056132, F32 DK089717. doi:10.1016/j.appet.2011.05.125
S5
Expectation for palatable food. A process that generates gradually in the brain and correlates with behaviour A.S. BLANCAS-VELáZQUEZ, K. RODRIGUEZ, C. ESCOBAR UNAM, Facultad de Medicina, Departamento de Anatomia, Mexico, Mexico Purpose: Characterize in reward related nuclei such as Nucleus Accumbens and Prefrontal Cortex the process to develop neuronal and behavioural activation anticipating chocolate. Methods: Neuronal activation:Male Wistar rats were divided in two groups, those who were sacrificed after ingestion of chocolate and those sacrificed when they were expecting the palatable food. Sacrifice was on days: 1, 2, 3, 5 and 8 of eating chocolate. Brain was processed for c-Fos immunohistochemistry as marker of activation. The positive cells were counted. Behavioral assessment: We designed a wire box cube in which we put the 5 g. piece of chocolate. It allowed rats to see and smell the chocolate but it was impossible to touch scratch or bite it. The motivation was determined measuring the approaches, contacts and handling of the box during 5 min before time for chocolate. Results: Rats sacrificed after ingestion of chocolate showed increased neuronal activation in all days tested. The “expectant” group showed progressive neuronal activation that increases depending on the number of days of previous ingestion of chocolate. There was a correlation between the results of the group of expectation and the behaviour of the group of rats that worked to get the chocolate. Conclusions: The acquisition of a perseverant behaviour where the animal looks for the pleasurable stimulus develops gradually and it involves both NAcc and PFCx. Supported by: CONACyT 82462 and PAPIIT UNAM IN-224911. doi:10.1016/j.appet.2011.05.126 Effects of prenatal diet on food preference and ethanol intake in offspring M.E. BOCARSLY 1 , J. HAUCA 1 , J.R. BARSON 2 , S.F. LEIBOWITZ 2 , B.G. HOEBEL 1 , N.M. AVENA 1,3 1 Princeton University, Princeton, USA 2 Rockefeller University, NY, USA 3 University of Florida, Gainesville, USA A high-fat diet (HFD) in utero can lead to changes in hypothalamic galanin gene expression as well as hyperlipidemia, preference for fat, and increased body weight. Galanin and circulating triglycerdies (TG) have also been linked to ethanol intake. Thus, offspring of HFD-consuming dams may have avidity for ethanol, and offspring of dams fed other foods that are known to increase TG levels may also have increased body weight, and preference for fat and ethanol. Exp. 1: Dams were fed either a HFD or a control diet. Female offspring were fed standard chow and trained to drink unsweetened ethanol starting on P25. Female rats born to HFD-consuming dams had increased ethanol intake, developed a preference for ethanol over water, and had increased serum TG levels compared to females born to control dams. Exp. 2: Dams were fed standard chow, or standard chow with access to a 16% high-fructose corn syrup (HFCS) or a 10% sucrose solution. Offspring were fed standard chow. As early as P15, rats born to HFCS-consuming dams weighed significantly more than rats born to the control groups, and they showed differences in preference for HFD and HFCS compared with the control groups. Female offspring born to HFCS-consuming dams also showed a preference for ethanol. Collectively, these data suggest prenatal exposure to TG-promoting diets can lead to physiological and behavioral changes related to body weight, food preference and the consumption of ethanol. Supported by: NIDA, NIAAA and National Eating Disorders Association. doi:10.1016/j.appet.2011.05.127
Viral-mediated overexpression of NPY in the dorsomedial hypothalamus causes hyperphagia and obesity in Sprague Dawley rats S. BI 1 , K.A. SCOTT 1,2 , P.T. CHAO 1 , Y.J. KIM 1 , C. DE LA SERRE 1 , T.H. MORAN 1 1 Johns Hopkins University School of Medicine, Baltimore, USA 2 University of Cincinnati, Cincinnati, USA Previous reports have shown NPY overexpression in the dorsomedial hypothalamus (DMH) in a number of obesity models of rodents. Whether this overexpression plays a causative role in these animal models is not established. To this end, we generated a recombinant vector of adeno-associated virus (AAV)-mediated expression of NPY (AAVNPY) and determined the effect of DMH NPY overexpression on energy homeostasis in adult Sprague Dawley rats. Animals received DMH injections of AAVNPY and food intake and body weight were monitored for 16 weeks. We found that food intake and body weight were significantly increased in NPY overexpression rats compared to rats receiving GFP control vectors. Meal pattern analysis revealed that DMH NPY overexpression specifically increased meal size during the dark period, leading to hyperphagia. NPY overexpression significantly increased fat mass as determined in the areas of inguinal subcutaneous and epididymal white fat and interscapular brown fat. Moreover, while high fat diet access induced obesity in control rats, DMH NPY overexpression exacerbated diet-induced increases in food intake and body weight and resulted in even greater increases in inguinal fat. This overexpression also caused increases in plasma leptin and insulin levels. Together, our results demonstrate that DMH NPY overexpression can result in obesity and implicates this overexpression as causal in a number of obesity models. Supported by: NIH R01DK074269 (to S.B.). doi:10.1016/j.appet.2011.05.124 Inhibitory effects of insulin in the dorsal motor nucleus of the vagus C.B. BLAKE, B.N. SMITH Department of Physiology, College of Medicine, University of Kentucky, Lexington, USA Insulin, which is critical to glucose regulation in the body, crosses the blood brain barrier and is transported into the brainstem over twice as rapidly as into whole brain and may affect glucose regulation via central mechanisms. Brainstem nuclei, specifically the dorsal motor nucleus of the vagus (DMV), are essential for visceral parasympathetic function. Pathologies in which insulin is dysregulated, including diabetes, can disrupt this circuit, leading to gastric and other autonomic dysfunction. Insulin receptors (IRs) are expressed in the DMV, and preliminary data indicates that IRs are located in proximity to gastric-projecting DMV cells. We used whole-cell patch-clamp recordings in brainstem slices to identify effects of insulin on synaptic input to DMV neurons. Insulin significantly reduced the frequency of action potential firing (APs), spontaneous excitatory post-synaptic currents (sEPSCs), and miniature EPSCs, with no change in amplitude. Insulin also reduced sEPSC and AP frequency in a subset of identified gastricrelated DMV neurons. Insulin activity was dependent on the KATP channel and PI3-kinase activity, because the effects of insulin on sEPSC frequency were eliminated in the presence of a KATP channel antagonist, tolbutamide or the PI3-kinase inhibitor, wortmannin. These results suggest that insulin inhibits excitatory input to DMV neurons via a KATP channel- and PI3-kinase-dependent mechanism. Such regulation may influence glucose metabolism in the DMV and thus, autonomic visceral regulation. Supported by: R01 DK056132, F32 DK089717. doi:10.1016/j.appet.2011.05.125
S5
Expectation for palatable food. A process that generates gradually in the brain and correlates with behaviour A.S. BLANCAS-VELáZQUEZ, K. RODRIGUEZ, C. ESCOBAR UNAM, Facultad de Medicina, Departamento de Anatomia, Mexico, Mexico Purpose: Characterize in reward related nuclei such as Nucleus Accumbens and Prefrontal Cortex the process to develop neuronal and behavioural activation anticipating chocolate. Methods: Neuronal activation:Male Wistar rats were divided in two groups, those who were sacrificed after ingestion of chocolate and those sacrificed when they were expecting the palatable food. Sacrifice was on days: 1, 2, 3, 5 and 8 of eating chocolate. Brain was processed for c-Fos immunohistochemistry as marker of activation. The positive cells were counted. Behavioral assessment: We designed a wire box cube in which we put the 5 g. piece of chocolate. It allowed rats to see and smell the chocolate but it was impossible to touch scratch or bite it. The motivation was determined measuring the approaches, contacts and handling of the box during 5 min before time for chocolate. Results: Rats sacrificed after ingestion of chocolate showed increased neuronal activation in all days tested. The “expectant” group showed progressive neuronal activation that increases depending on the number of days of previous ingestion of chocolate. There was a correlation between the results of the group of expectation and the behaviour of the group of rats that worked to get the chocolate. Conclusions: The acquisition of a perseverant behaviour where the animal looks for the pleasurable stimulus develops gradually and it involves both NAcc and PFCx. Supported by: CONACyT 82462 and PAPIIT UNAM IN-224911. doi:10.1016/j.appet.2011.05.126 Effects of prenatal diet on food preference and ethanol intake in offspring M.E. BOCARSLY 1 , J. HAUCA 1 , J.R. BARSON 2 , S.F. LEIBOWITZ 2 , B.G. HOEBEL 1 , N.M. AVENA 1,3 1 Princeton University, Princeton, USA 2 Rockefeller University, NY, USA 3 University of Florida, Gainesville, USA A high-fat diet (HFD) in utero can lead to changes in hypothalamic galanin gene expression as well as hyperlipidemia, preference for fat, and increased body weight. Galanin and circulating triglycerdies (TG) have also been linked to ethanol intake. Thus, offspring of HFD-consuming dams may have avidity for ethanol, and offspring of dams fed other foods that are known to increase TG levels may also have increased body weight, and preference for fat and ethanol. Exp. 1: Dams were fed either a HFD or a control diet. Female offspring were fed standard chow and trained to drink unsweetened ethanol starting on P25. Female rats born to HFD-consuming dams had increased ethanol intake, developed a preference for ethanol over water, and had increased serum TG levels compared to females born to control dams. Exp. 2: Dams were fed standard chow, or standard chow with access to a 16% high-fructose corn syrup (HFCS) or a 10% sucrose solution. Offspring were fed standard chow. As early as P15, rats born to HFCS-consuming dams weighed significantly more than rats born to the control groups, and they showed differences in preference for HFD and HFCS compared with the control groups. Female offspring born to HFCS-consuming dams also showed a preference for ethanol. Collectively, these data suggest prenatal exposure to TG-promoting diets can lead to physiological and behavioral changes related to body weight, food preference and the consumption of ethanol. Supported by: NIDA, NIAAA and National Eating Disorders Association. doi:10.1016/j.appet.2011.05.127