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Satiety signals from the gut
T.H. Moran / Appetite 51 (2010) 350–412
Satiety signals from the gut C. FEINLE-BISSET . University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia The gastrointestinal (GI) tract plays a vital role in the regulation of energy intake. While a high dietary fat intake leads to overconsumption, fat also has potent effects on those GI functions that favour the suppression of energy intake. The presence of fat in the small intestine slows gastric emptying, distending the stomach and increasing fullness, and associated with the modulation of motor patterns in the GI region, particularly stimulation of pressures in the pylorus. Interaction of fat with small intestinal receptors also triggers the release of gut hormones, including CCK, PYY and GLP1, and the suppression of ghrelin. All these changes are thought to contribute to the suppression of energy intake. The effects of fat on energy intake and GI function are abolished when fat digestion is inhibited and dependent on fatty acid chain length as well as the length and/or region of intestine exposed to nutrient. An important role for distal small intestinal feedback is demonstrated by the success of gastric bypass surgery, directing nutrients to the distal gut, in accomplishing significant weight loss. GI function can adapt to excess nutrient exposure, rendering it less sensitive to nutrient and/or hormonal stimuli. Since obese individuals have an increased energy/nutrient intake, they may have a reduced ability to sense gut stimuli, associated with reduced modulation of gut functions, thus, compromising their capacity to limit their energy intake. Strategies are required to stimulate those aspects of GI function that are associated with the suppression of energy intake, ultimately resulting in sustained weight loss in obesity. doi:10.1016/j.appet.2008.04.081
Rats do not interrupt food consumption to react to noxious heat stimulation H. FOO ∗ , P. MASON. Department of Neurobiology, University of Chicago, Chicago, USA This study aimed to identify key factors that affect the selection between ingestion and responding to a noxious stimulus. Experiment 1 examined if this selection is impacted by appetite, and the palatability and nutritive content of the food. Intraoral infusions of neutral (water) or palatable and preferred (sucrose and saccharin) solutions suppressed paw withdrawals to the same extent as occurred when rats ate chocolate, showing that suppression occurs even when ingestion is induced and when the food has no caloric value. In contrast, ingestion of non-preferred (salt) or aversive (quinine) solutions produced no withdrawal suppression. During chocolate ingestion, paw licks were almost completely suppressed, presumably because paw-licking would require putting down the chocolate morsel. Paw licks were partially suppressed during intraorally induced ingestion of water, sucrose, and saccharin, and not suppressed during ingestion of salt or quinine. In experiment 2, the impact of nausea on the defense of eating was tested. During chocolate ingestion following infusion of neutral (water) or non-preferred (salt) solution, paw withdrawals and licks were suppressed. Interruptions to eating were brief and comparable to those seen during chocolate ingestion without any infusions. However, during chocolate eating following quinine infusion, paw withdrawals to noxious heat were no longer suppressed and eating was interrupted for a longer time. Yet, paw licks remained suppressed. Thus, although rats ate with hesitation following possible quinine-induced nausea, they were reluctant to relinquish their chocolate. doi:10.1016/j.appet.2008.04.082
365
Sex differences: Behavioral, metabolic and stress consequences of a female bias visible burrow system M.T. FOSTER ∗ , S.J. MELHORN, K.A. SCOTT, E.G. KRAUSE, S.C. WOODS, R.R. SAKAI. University of Cincinnati, Cincinnati, USA The visible burrow system (VBS) is an ethological model used to investigate effects of social stress consequential of hierarchy formation. Previous studies have characterized behavioral and physiological differences resultant of dominant (DOM)/subordinate (SUB) formation, but only in male rats. Female social behavior and ensuing physiological alterations have not been investigated. Here we ask, will female rats form a hierarchy similar to males resulting in decreases in body/lipid mass, insulin and leptin and increases basal corticosterone in SUB? This was accomplished via 14 day interaction in female bias colony consisting of four females and two males, controls are shared cage female and male. Restraint stress test was given to females on day 13. Females, although not as aggressive as males, formed a hierarchy with DOM displaying offensive behaviors (chasing, on-top-of and chamber guarding) and SUB defensive behaviors (flight and on-the-back). Unlike males, females, regardless of status, did not have a decrease in body mass. SUB females gained body mass significantly faster than DOM females, whereas SUB males had significantly suppressed body mass compared with DOM and control males. The alterations in body mass are reflected in total fat pad mass in males with SUB having significantly decreased total fat mass compared with DOM and controls. In females, however, DOM have significantly increased total fat pad mass compared with controls. These data suggest social hierarchy behavior is similar among females and males, but physiological responses are opposing. doi:10.1016/j.appet.2008.04.083
Targeted enhancement of oleoylethanolamide mobilization in proximal small intestine induces across-meal satiety in rats J. FU 1,∗ , J. KIM 1 , F. OVEISI 1 , D. PIOMELLI 1,2 . 1 University of California, Irvine, Irvine, USA 2 Italian Institute of Technology, Genova, Italy Pharmacological administration of the natural lipid amide, oleoylethanolamide (OEA), inhibits food intake in rodents by prolonging latency to feed and post-meal interval. This anorexic effect is mediated by activation of peroxisome proliferatoractivated receptors (PPAR-␣). Food intake stimulates mucosal cells in duodenum and jejunum to generate OEA, suggesting that this lipid-derived messenger may act as a local satiety hormone in the upper proximal small intestine. As a test of this hypothesis, here we examined whether targeted enhancement of small-intestinal OEA production affects feeding behavior in rats. We constructed an adenoviral vector that directs overexpression of N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD), which catalyses the production of OEA from NAPE. Intraduodenal injection of this vector (Ad-NPLD) resulted in a timedependent increase in NAPE-PLD expression and OEA production, which was restricted to the proximal small intestine. No such effect was observed after administration of control vector. Enhanced OEA mobilization in Ad-NPLD-injected animals was temporally associated with increased expression of two PPAR-␣ target genes (PPAR-␣ and CD36) and with decreased food intake. This hypophagic phenotype was attributable to increase feeding latency and post-meal interval, rather then decreased meal size. The results suggest that localized changes in small-intestinal OEA production are sufficient to induce in rats a state of across-meal satiety. doi:10.1016/j.appet.2008.04.084
Satiety signals from the gut C. FEINLE-BISSET . University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, Australia The gastrointestinal (GI) tract plays a vital role in the regulation of energy intake. While a high dietary fat intake leads to overconsumption, fat also has potent effects on those GI functions that favour the suppression of energy intake. The presence of fat in the small intestine slows gastric emptying, distending the stomach and increasing fullness, and associated with the modulation of motor patterns in the GI region, particularly stimulation of pressures in the pylorus. Interaction of fat with small intestinal receptors also triggers the release of gut hormones, including CCK, PYY and GLP1, and the suppression of ghrelin. All these changes are thought to contribute to the suppression of energy intake. The effects of fat on energy intake and GI function are abolished when fat digestion is inhibited and dependent on fatty acid chain length as well as the length and/or region of intestine exposed to nutrient. An important role for distal small intestinal feedback is demonstrated by the success of gastric bypass surgery, directing nutrients to the distal gut, in accomplishing significant weight loss. GI function can adapt to excess nutrient exposure, rendering it less sensitive to nutrient and/or hormonal stimuli. Since obese individuals have an increased energy/nutrient intake, they may have a reduced ability to sense gut stimuli, associated with reduced modulation of gut functions, thus, compromising their capacity to limit their energy intake. Strategies are required to stimulate those aspects of GI function that are associated with the suppression of energy intake, ultimately resulting in sustained weight loss in obesity. doi:10.1016/j.appet.2008.04.081
Rats do not interrupt food consumption to react to noxious heat stimulation H. FOO ∗ , P. MASON. Department of Neurobiology, University of Chicago, Chicago, USA This study aimed to identify key factors that affect the selection between ingestion and responding to a noxious stimulus. Experiment 1 examined if this selection is impacted by appetite, and the palatability and nutritive content of the food. Intraoral infusions of neutral (water) or palatable and preferred (sucrose and saccharin) solutions suppressed paw withdrawals to the same extent as occurred when rats ate chocolate, showing that suppression occurs even when ingestion is induced and when the food has no caloric value. In contrast, ingestion of non-preferred (salt) or aversive (quinine) solutions produced no withdrawal suppression. During chocolate ingestion, paw licks were almost completely suppressed, presumably because paw-licking would require putting down the chocolate morsel. Paw licks were partially suppressed during intraorally induced ingestion of water, sucrose, and saccharin, and not suppressed during ingestion of salt or quinine. In experiment 2, the impact of nausea on the defense of eating was tested. During chocolate ingestion following infusion of neutral (water) or non-preferred (salt) solution, paw withdrawals and licks were suppressed. Interruptions to eating were brief and comparable to those seen during chocolate ingestion without any infusions. However, during chocolate eating following quinine infusion, paw withdrawals to noxious heat were no longer suppressed and eating was interrupted for a longer time. Yet, paw licks remained suppressed. Thus, although rats ate with hesitation following possible quinine-induced nausea, they were reluctant to relinquish their chocolate. doi:10.1016/j.appet.2008.04.082
365
Sex differences: Behavioral, metabolic and stress consequences of a female bias visible burrow system M.T. FOSTER ∗ , S.J. MELHORN, K.A. SCOTT, E.G. KRAUSE, S.C. WOODS, R.R. SAKAI. University of Cincinnati, Cincinnati, USA The visible burrow system (VBS) is an ethological model used to investigate effects of social stress consequential of hierarchy formation. Previous studies have characterized behavioral and physiological differences resultant of dominant (DOM)/subordinate (SUB) formation, but only in male rats. Female social behavior and ensuing physiological alterations have not been investigated. Here we ask, will female rats form a hierarchy similar to males resulting in decreases in body/lipid mass, insulin and leptin and increases basal corticosterone in SUB? This was accomplished via 14 day interaction in female bias colony consisting of four females and two males, controls are shared cage female and male. Restraint stress test was given to females on day 13. Females, although not as aggressive as males, formed a hierarchy with DOM displaying offensive behaviors (chasing, on-top-of and chamber guarding) and SUB defensive behaviors (flight and on-the-back). Unlike males, females, regardless of status, did not have a decrease in body mass. SUB females gained body mass significantly faster than DOM females, whereas SUB males had significantly suppressed body mass compared with DOM and control males. The alterations in body mass are reflected in total fat pad mass in males with SUB having significantly decreased total fat mass compared with DOM and controls. In females, however, DOM have significantly increased total fat pad mass compared with controls. These data suggest social hierarchy behavior is similar among females and males, but physiological responses are opposing. doi:10.1016/j.appet.2008.04.083
Targeted enhancement of oleoylethanolamide mobilization in proximal small intestine induces across-meal satiety in rats J. FU 1,∗ , J. KIM 1 , F. OVEISI 1 , D. PIOMELLI 1,2 . 1 University of California, Irvine, Irvine, USA 2 Italian Institute of Technology, Genova, Italy Pharmacological administration of the natural lipid amide, oleoylethanolamide (OEA), inhibits food intake in rodents by prolonging latency to feed and post-meal interval. This anorexic effect is mediated by activation of peroxisome proliferatoractivated receptors (PPAR-␣). Food intake stimulates mucosal cells in duodenum and jejunum to generate OEA, suggesting that this lipid-derived messenger may act as a local satiety hormone in the upper proximal small intestine. As a test of this hypothesis, here we examined whether targeted enhancement of small-intestinal OEA production affects feeding behavior in rats. We constructed an adenoviral vector that directs overexpression of N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD), which catalyses the production of OEA from NAPE. Intraduodenal injection of this vector (Ad-NPLD) resulted in a timedependent increase in NAPE-PLD expression and OEA production, which was restricted to the proximal small intestine. No such effect was observed after administration of control vector. Enhanced OEA mobilization in Ad-NPLD-injected animals was temporally associated with increased expression of two PPAR-␣ target genes (PPAR-␣ and CD36) and with decreased food intake. This hypophagic phenotype was attributable to increase feeding latency and post-meal interval, rather then decreased meal size. The results suggest that localized changes in small-intestinal OEA production are sufficient to induce in rats a state of across-meal satiety. doi:10.1016/j.appet.2008.04.084