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Disgust proneness and associated neural substrates in obesity.
Watkins TJ, Di Iorio CR, Olatunji BO, Benningfield MM, Blackford JU, Dietrich MS, Bhatia M, Theiss JD, Salomon RM, Niswender K, Cowan RL
(2016) Soc Cogn Affect Neurosci 11: 458-65
MeSH Terms: Adult, Body Mass Index, Brain Mapping, Cerebral Cortex, Eating, Emotions, Female, Food, Food Contamination, Functional Laterality, Humans, Hunger, Hyperphagia, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Obesity, Photic Stimulation
Show Abstract · Added February 15, 2016
Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese, 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised and a functional magnetic resonance imaging paradigm where images from 4 categories (food, contaminates, contaminated food or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score = 14.7) compared with the lean group (mean score = 17.6, P = 0.026). The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r = -0.59) compared with a positive correlation in the lean group (r = 0.65). Given these body mass index-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images, it is likely that altered Disgust Sensitivity may contribute to obesity.
© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Chronic overeating impairs hepatic glucose uptake and disposition.
Coate KC, Kraft G, Shiota M, Smith MS, Farmer B, Neal DW, Williams P, Cherrington AD, Moore MC
(2015) Am J Physiol Endocrinol Metab 308: E860-7
MeSH Terms: Animals, Blood Glucose, C-Peptide, Chronic Disease, Dogs, Eating, Glucose, Glucose Clamp Technique, Hyperphagia, Insulin, Liver, Male, Weight Gain
Show Abstract · Added July 24, 2015
Dogs consuming a hypercaloric high-fat and -fructose diet (52 and 17% of total energy, respectively) or a diet high in either fructose or fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) and glycogen deposition in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery. The effect of a hypercaloric diet containing neither fructose nor excessive fat has not been examined. Dogs with an initial weight of ≈25 kg consumed a chow and meat diet (31% protein, 44% carbohydrate, and 26% fat) in weight-maintaining (CTR; n = 6) or excessive (Hkcal; n = 7) amounts for 4 wk (cumulative weight gain 0.0 ± 0.3 and 1.5 ± 0.5 kg, respectively, P < 0.05). They then underwent clamp studies with infusions of somatostatin and intraportal insulin (4× basal) and glucagon (basal). The hepatic glucose load was doubled with peripheral (Pe) glucose infusion for 90 min (P1) and intraportal glucose at 4 mg·kg(-1)·min(-1) plus Pe glucose for the final 90 min (P2). NHGU was blunted (P < 0.05) in Hkcal during both periods (mg·kg(-1)·min(-1); P1: 1.7 ± 0.2 vs. 0.3 ± 0.4; P2: 3.6 ± 0.3 vs. 2.3 ± 0.4, CTR vs. Hkcal, respectively). Terminal hepatic glucokinase catalytic activity was reduced nearly 50% in Hkcal vs. CTR (P < 0.05), although glucokinase protein did not differ between groups. In Hkcal vs. CTR, liver glycogen was reduced 27% (P < 0.05), with a 91% increase in glycogen phosphorylase activity (P < 0.05) but no significant difference in glycogen synthase activity. Thus, Hkcal impaired NHGU and glycogen synthesis compared with CTR, indicating that excessive energy intake, even if the diet is balanced and nutritious, negatively impacts hepatic glucose metabolism.
Copyright © 2015 the American Physiological Society.
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4 Members
2 Resources
13 MeSH Terms
Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis.
Berglund ED, Liu C, Sohn JW, Liu T, Kim MH, Lee CE, Vianna CR, Williams KW, Xu Y, Elmquist JK
(2013) J Clin Invest 123: 5061-70
MeSH Terms: Animals, Appetite Depressants, Body Weight, Dietary Fats, Dietary Sucrose, Drug Resistance, Energy Metabolism, Feeding Behavior, Female, Glucagon, Glucose, Homeostasis, Hyperglycemia, Hyperinsulinism, Hyperphagia, Insulin, Insulin Resistance, Insulin Secretion, Male, Mice, Mice, Knockout, Neurons, Obesity, Pro-Opiomelanocortin, Receptor, Serotonin, 5-HT2C, Recombinant Fusion Proteins, Serotonin, Serotonin Receptor Agonists
Show Abstract · Added July 21, 2014
Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.
1 Communities
0 Members
0 Resources
28 MeSH Terms
Melanocortin-4 receptor mutations paradoxically reduce preference for palatable foods.
Panaro BL, Cone RD
(2013) Proc Natl Acad Sci U S A 110: 7050-5
MeSH Terms: Animals, Body Weight, Diet, High-Fat, Dietary Carbohydrates, Eating, Food Preferences, Gene Deletion, Hyperphagia, Male, Mice, Mice, Knockout, Obesity, Receptor, Melanocortin, Type 4
Show Abstract · Added May 27, 2014
Haploinsufficiency of the melanocortin-4 receptor (MC4R) results in melanocortin obesity syndrome, the most common monogenic cause of severe early onset obesity in humans. The syndrome, which produces measurable hyperphagia, has focused attention on the role of MC4R in feeding behavior and macronutrient intake. Studies show that inhibition of MC4R signaling can acutely increase the consumption of high-fat foods. The current study examines the chronic feeding preferences of mice with deletion of one or both alleles of the MC4R to model the human syndrome. Using two-choice diet paradigms with high-fat or high-carbohydrate foods alongside normal chow, we show, paradoxically, that deletion of one allele has no effect, whereas deletion of both alleles of the MC4R actually decreases preference for palatable high-fat and high-sucrose foods, compared with wild-type mice. Nonetheless, we observed hyperphagic behavior from increased consumption of the low-fat standard chow when either heterozygous or homozygous mutant animals were presented with dietary variety. Thus, decreased MC4R signaling in melanocortin obesity syndrome consistently yields hyperphagia irrespective of the foods provided, but the hyperphagia appears driven by variety and/or novelty, rather than by a preference for high-fat or high-carbohydrate foodstuffs.
0 Communities
1 Members
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13 MeSH Terms
Central nervous system neuropeptide Y signaling via the Y1 receptor partially dissociates feeding behavior from lipoprotein metabolism in lean rats.
Rojas JM, Stafford JM, Saadat S, Printz RL, Beck-Sickinger AG, Niswender KD
(2012) Am J Physiol Endocrinol Metab 303: E1479-88
MeSH Terms: Animals, Appetite Regulation, Behavior, Animal, Central Nervous System, Humans, Hyperphagia, Infusions, Intraventricular, Lipoproteins, VLDL, Liver, Male, Nerve Tissue Proteins, Neurons, Neuropeptide Y, Obesity, Protein Isoforms, Rats, Rats, Long-Evans, Receptors, Neuropeptide Y, Recombinant Proteins, Signal Transduction, Triglycerides
Show Abstract · Added December 10, 2013
Elevated plasma triglyceride (TG) levels contribute to an atherogenic dyslipidemia that is associated with obesity, diabetes, and metabolic syndrome. Numerous models of obesity are characterized by increased central nervous system (CNS) neuropeptide Y (NPY) tone that contributes to excess food intake and obesity. Previously, we demonstrated that intracerebroventricular (icv) administration of NPY in lean fasted rats also elevates hepatic production of very low-density lipoprotein (VLDL)-TG. Thus, we hypothesize that elevated CNS NPY action contributes to not only the pathogenesis of obesity but also dyslipidemia. Here, we sought to determine whether the effects of NPY on feeding and/or obesity are dissociable from effects on hepatic VLDL-TG secretion. Pair-fed, icv NPY-treated, chow-fed Long-Evans rats develop hypertriglyceridemia in the absence of increased food intake and body fat accumulation compared with vehicle-treated controls. We then modulated CNS NPY signaling by icv injection of selective NPY receptor agonists and found that Y1, Y2, Y4, and Y5 receptor agonists all induced hyperphagia in lean, ad libitum chow-fed Long-Evans rats, with the Y2 receptor agonist having the most pronounced effect. Next, we found that at equipotent doses for food intake NPY Y1 receptor agonist had the most robust effect on VLDL-TG secretion, a Y2 receptor agonist had a modest effect, and no effect was observed for Y4 and Y5 receptor agonists. These findings, using selective agonists, suggest the possibility that the effect of CNS NPY signaling on hepatic VLDL-TG secretion may be relatively dissociable from effects on feeding behavior via the Y1 receptor.
1 Communities
2 Members
0 Resources
21 MeSH Terms
Nutrient excess stimulates β-cell neogenesis in zebrafish.
Maddison LA, Chen W
(2012) Diabetes 61: 2517-24
MeSH Terms: Animals, Animals, Genetically Modified, Cell Count, Cell Differentiation, Cell Proliferation, Diet, Food, Homeodomain Proteins, Hyperphagia, Insulin, Insulin-Like Growth Factor I, Insulin-Secreting Cells, Nutritional Status, Signal Transduction, Transcription Factors, Zebrafish, Zebrafish Proteins
Show Abstract · Added December 5, 2013
Persistent nutrient excess results in a compensatory increase in the β-cell number in mammals. It is unknown whether this response occurs in nonmammalian vertebrates, including zebrafish, a model for genetics and chemical genetics. We investigated the response of zebrafish β-cells to nutrient excess and the underlying mechanisms by culturing transgenic zebrafish larvae in solutions of different nutrient composition. The number of β-cells rapidly increases after persistent, but not intermittent, exposure to glucose or a lipid-rich diet. The response to glucose, but not the lipid-rich diet, required mammalian target of rapamycin activity. In contrast, inhibition of insulin/IGF-1 signaling in β-cells blocked the response to the lipid-rich diet, but not to glucose. Lineage tracing and marker expression analyses indicated that the new β-cells were not from self-replication but arose through differentiation of postmitotic precursor cells. On the basis of transgenic markers, we identified two groups of newly formed β-cells: one with nkx2.2 promoter activity and the other with mnx1 promoter activity. Thus, nutrient excess in zebrafish induces a rapid increase in β-cells though differentiation of two subpopulations of postmitotic precursor cells. This occurs through different mechanisms depending on the nutrient type and likely involves paracrine signaling between the differentiated β-cells and the precursor cells.
1 Communities
1 Members
0 Resources
17 MeSH Terms
Dopamine-based reward circuitry responsivity, genetics, and overeating.
Stice E, Yokum S, Zald D, Dagher A
(2011) Curr Top Behav Neurosci 6: 81-93
MeSH Terms: Animals, Brain, Catechol O-Methyltransferase, Dopamine, Dopamine Plasma Membrane Transport Proteins, Ghrelin, Humans, Hyperphagia, Obesity, Proto-Oncogene Proteins c-akt, Receptors, Dopamine D2, Receptors, Dopamine D4, Reward
Show Abstract · Added May 27, 2014
Data suggest that low levels of dopamine D2 receptors and attenuated responsivity of dopamine-target regions to food intake is associated with increased eating and elevated weight. There is also growing (although mixed) evidence that genotypes that appear to lead to reduced dopamine signaling (e.g., DRD2, DRD4, and DAT) and certain appetite-related hormones and peptides (e.g., ghrelin, orexin A, leptin) moderate the relation between dopamine signaling, overeating, and obesity. This chapter reviews findings from studies that have investigated the relation between dopamine functioning and food intake and how certain genotypes and appetite-related hormones and peptides affect this relation.
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1 Members
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13 MeSH Terms
Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse.
Srisai D, Gillum MP, Panaro BL, Zhang XM, Kotchabhakdi N, Shulman GI, Ellacott KL, Cone RD
(2011) Endocrinology 152: 890-902
MeSH Terms: Amidohydrolases, Animals, Basic Helix-Loop-Helix Transcription Factors, Dietary Fats, Female, Gene Expression Regulation, Heterozygote, Hyperphagia, Male, Mice, Mice, Knockout, Mutation, Receptor, Melanocortin, Type 1, Receptor, Melanocortin, Type 4, Repressor Proteins
Show Abstract · Added December 10, 2013
Defective melanocortin signaling causes hyperphagic obesity in humans and the melanocortin-4 receptor knockout mouse (MC4R(-/-)). The human disease most commonly presents, however, as haploinsufficiency of the MC4R. This study validates the MC4R(+/-) mouse as a model of the human disease in that, like the MC4R(-/-), the MC4R(+/-) mouse also exhibits a sustained hyperphagic response to dietary fat. Furthermore, both saturated and monounsaturated fats elicit this response. N-acylphosphatidylethanolamine (NAPE) is a signaling lipid induced after several hours of high-fat feeding, that, if dysregulated, might explain the feeding behavior in melanocortin obesity syndrome. Remarkably, however, MC4R(-/-) mice produce elevated levels of NAPE and are fully responsive to the anorexigenic activity of NAPE and oleoylethanolamide. Interestingly, additional differences in N-acylethanolamine (NAE) biochemistry were seen in MC4R(-/-) animals, including reduced plasma NAE levels and elevated hypothalamic levels of fatty acid amide hydrolase expression. Thus, while reduced expression of NAPE or NAE does not explain the high-fat hyperphagia in the melanocortin obesity syndrome, alterations in this family of signaling lipids are evident. Analysis of the microstructure of feeding behavior in response to dietary fat in the MC4R(-/-) and MC4R(+/-) mice indicates that the high-fat hyperphagia involves defective satiation and an increased rate of food intake, suggesting defective satiety signaling and enhanced reward value of dietary fat.
0 Communities
2 Members
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15 MeSH Terms