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ABSTRACT: BACKGROUND: Whether and how sex and age affect bariatric-surgery outcome is poorly understood. Estrogens regulate body composition in women and animals, and increase weight loss in a rodent model of gastric bypass, suggesting that premenopausal women may lose more weight following bariatric surgery. METHODS: One thousand three hundred fifty-six female gastric-bypass or gastric-banding patients were retrospectively grouped as 20-45 years old (presumptively premenopausal; n = 1,199) and 55-65 years old (presumptively postmenopausal; n = 157). Mixed-model ANCOVA followed by Bonferroni-corrected t tests were used to categorically test the effect of age on percent excess body weight loss (%EBWL) at 1 and 2 years post-surgery, controlling for preoperative EBW and surgery type. Age effects were also tested dimensionally in all women and in 289 male patients. RESULTS: Twenty- to forty-five-year-old women showed greater %EBWL 1 and 2 years post-surgery than 55-65-year-old women (p's < 0.0005). No age effect was detected in 20-25- vs. 30-35-, 30-35- vs. 40-45-, or 20-25- vs. 40-45-year-old women (p's > 0.2) This age effect was detected only after gastric banding, with 20-45-year-old women losing ∼7 kg more than 55-65-year-old women after 2 years. Dimensional analysis confirmed a significant inverse effect of age on bariatric surgery outcome in women, but did not detect any effect in men. CONCLUSIONS: Results indicate that 55-65-year-old women lose less weight than 20-45-year-old women in the initial 2 years after bariatric surgery, especially gastric banding; this may be mediated by age- or menopause-associated changes in physical activity, energy expenditure, or energy intake.
Obesity Surgery 05/2013; · 3.29 Impact Factor
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ABSTRACT: Despite the fact that ∼85% of bariatric operations are performed in women, the effects of the reproductive axis function on outcome of bariatric surgery remain to be determined. Here we developed the first published model of Roux-en-Y gastric bypass (RYGB) in female rats. We show in ovariectomized rats receiving estradiol or control treatment that (1) RYGB-induced body weight loss and (2) the satiating efficacy of endogenous glucagon-like peptide-1 and cholecystokinin satiation were significantly increased in estradiol-treated rats. These data are relevant to the care of obese women, in particular perimenopausal women, undergoing bariatric surgery.
Gastroenterology 05/2012; 143(2):325-7.e2. · 11.68 Impact Factor
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ABSTRACT: Because protein hydrolysates are digested faster than the corresponding proteins, they may increase or hasten the acute eating-inhibitory effect of protein. Potential mediating mechanisms include accelerated or greater release of satiating gut peptides and activation of metabolic signals that inhibit eating. We tested these hypotheses in adult male rats that were surgically equipped with intragastric (IG) cannulas and adapted to 30-min test meals at dark onset after 14-h food deprivation. Equiosmotic 12 ml loads of saline-urea control (C), 13.6% pea protein (PP), or 13.6% PP hydrolysate (PPH, DSM/DFS, Delft, The Netherlands) solutions were IG infused in 1 min just before test meals. PPH reduced test-meal size compared to C more than PP (-3.8±0.3 g vs. -2.6±0.4 g; P<0.0001). Plasma glutamate increased more after PPH than PP (P<0.0001). Plasma lactate, alanine, insulin, glucagon, GLP-1 and paracetemol (an index of gastric emptying) all increased similarly, and glucose decreased similarly, after PPH or PP. Finally, PPH still reduced test-meal size more than PP (-4.6±0.3 g vs. -3.1±0.4 g; P<0.001) in rats after subdiaphragmatic vagal deafferentation, indicating that abdominal vagal afferents are not necessary for the eating-inhibitory effects of PP and PPH and, by extension, that gut peptides whose satiating effects depend on intact vagal afferents (e.g., CCK and glucagon) do not play crucial roles. Thus, PPH reduced short-term food intake more than PP under our conditions, but the mechanism(s) involved remain unclear.
Physiology & Behavior 07/2011; 104(5):1041-7. · 2.87 Impact Factor
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ABSTRACT: Anorexia is an element of the acute-phase immune response. Its mechanisms remain poorly understood. Activation of inducible cyclooxygenase-2 (COX-2) in blood-brain-barrier endothelial cells and subsequent release of prostaglandins (e.g., prostaglandin E2, PGE2) may be involved. Therefore, we sought to relate the effects of prostaglandins on the anorexia following gram-negative bacterial lipopolysaccharide treatment (LPS) to neural activity in the dorsal and median raphe nuclei (DRN and MnR) in rats. COX-2 antagonist (NS-398, 10mg/kg; IP) administration prior to LPS (100μg/kg; IP) prevented anorexia and reduced c-Fos expression the DRN, MnR, nucleus tractus solitarii and several related forebrain areas. These data indicate that COX-2-mediated prostaglandin synthesis is necessary for LPS anorexia and much of the initial LPS-induced neural activation. Injection of NS-398 into the DRN and MnR (1ng/site) attenuated LPS-induced anorexia to nearly the same extent as IP NS-398, suggesting that prostaglandin signaling in these areas is necessary for LPS anorexia. Because the DRN and MnR are sources of major serotonergic projections to the forebrain, these data suggest that serotonergic neurons originating in the midbrain raphe play an important role in acute-phase response anorexia.
Pharmacology Biochemistry and Behavior 04/2011; 99(3):437-43. · 2.53 Impact Factor
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ABSTRACT: Peripheral GLP-1 is produced by post-translational processing of pro-glucagon in enteroendocrine L-cells and is released in response to luminal nutrient (primarily carbohydrate and fat) stimulation. GLP-1 is well known for its potent insulinotropic and gluco-regulatory effects. GLP-1 receptors (GLP-1R) are expressed in the periphery and in several brain areas that are implicated in the control of eating. Both central and peripheral administration of GLP-1 have been shown to reduce food intake. Unresolved, however, is whether these effects reflect functions of endogenous GLP-1. Data collected in our laboratory indicate that in chow-fed rats: 1) Remotely controlled, intra-meal intravenous (IV) or intraperitoneal (IP) GLP-1 infusions selectively reduce meal size; 2) hindbrain GLP-1R activation is involved in the eating-inhibitory effect of IV infused GLP-1, whereas intact abdominal vagal afferents are necessary for the eating-inhibitory effect of IP, but not IV, infused GLP-1; 3) GLP-1 degradation in the liver prevents a systemic increase in endogenous GLP-1 during normal chow meals in rats; and 4) peripheral or hindbrain GLP-1R antagonism by exendin-9 does not affect spontaneous eating. Also, although our data indicate that peripheral GLP-1 can act in two different sites to inhibit eating, they argue against a role of systemic increases in endogenous GLP-1 in satiation in chow-fed rats. Therefore, further studies should examine whether a local paracrine action of GLP-1 in the intestine or and endocrine action in the hepatic-portal area is physiologically relevant for satiation.
Physiology & Behavior 02/2011; 105(1):71-6. · 2.87 Impact Factor
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ABSTRACT: Menopause is associated with increased adiposity, especially increased deposition of intra-abdominal (IA) adipose tissue (AT). This differs from common or 'dietary' obesity, i.e., obesity apparently due to environmentally stimulated overeating, in which IAAT and subcutaneous (S) AT increase in similar proportions. The effect of menopause on adiposity is thought to be due to the decreased secretion of ovarian estrogens. Ovariectomy in rats and other animals is a commonly used model of menopause. It is well known that ovariectomy increases adiposity and that this can be reversed by estradiol treatment, but whether ovariectomy selectively increases IAAT has not been measured directly. Therefore, we used micro-computed tomography (microCT) to investigate this question in both chow-fed and dietary-obese rats.
Ovariectomized, ovariectomized and estradiol treated, and sham-operated (intact) rats were fed chow or chow plus Ensure (Abbott Nutrition; n = 7/group). Total (T) AT, IAAT and SAT were measured periodically by microCT. Regional distribution of AT was expressed as IAAT as a percentage of TAT (%IAAT). Excesses in these measures were calculated with respect to chow-fed intact rats to control for normal maturational changes. Chemical analysis of fat was done in chow-fed intact and ovariectomized rats at study end. Data were analyzed by t-tests and planned comparisons.
Body mass, TAT, total fat mass, fat-free body mass, and %IAAT all increased in chow-fed intact rats during the 41 d study. In chow-fed rats, ovariectomy increased excess body mass, TAT, fat mass, fat-free body mass, and SAT, but had little effect on IAAT, in chow-fed rats, leading to a decrease in %IAAT. Ensure feeding markedly increased SAT, IAAT and TAT and did not significantly affect %IAAT. Ovariectomy had similar effects in Ensure-fed rats as in chow-fed rats, although less statistically reliable. Estradiol treatment prevented all the effects of ovariectomy.
Both ovariectomy in rats and menopause are associated with increased TAT. After ovariectomy, fat is preferentially deposited as SAT and lean body mass increases, whereas after menopause fat is preferentially deposited as IAAT and lean body mass decreases. These opposite effects of ovariectomy and menopause on regional AT distribution and lean body mass indicate that ovariectomy in rats is not a homologous model of menopause-associated changes in body composition that should be used with great caution in investigations of adiposity-related diseases.
Biology of sex differences. 01/2011; 2:6.
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ABSTRACT: This study examined how adiposity signals are related to adiposity during recovery from forced overweight (OW). Rats were rendered OW by chronic intragastric overfeeding (OW). Overfeeding was stopped when OW rats reached 126-129% of saline-infused normal-weight (NW) rats. Adipose tissue (AT) mass was estimated by computed tomography, and blood was drawn from chronic atrial cannulas throughout. Basal levels (i.e. after 2-3 h fasts late in the diurnal phase) of the hypothesized adiposity signals insulin, leptin, ghrelin, and amylin were assayed. OW rats gained approximately 130 g more body weight (BW) and approximately 100 g more AT mass during overfeeding. Plasma levels of insulin and leptin increased, whereas those of ghrelin decreased, linearly with AT mass; amylin did not change reliably. During recovery, OW rats' BW and AT mass decreased but were still elevated vs. NW rats after 39 d. OW rats' insulin returned to NW levels on d 1 of recovery and decreased below NW levels thereafter. Leptin was no longer elevated after d 8 of recovery. Ghrelin and amylin did not change reliably during recovery. Although AT mass decreased in OW rats during each intermeasurement interval between d 0 and d 23 of recovery, insulin and leptin did so during only the first interval (d 0-5). Insulin and leptin levels were exponentially related to AT mass during recovery. These data indicate that basal insulin, leptin, ghrelin, and amylin do not encode AT mass in rats dynamically regulating BW and adiposity during recovery from OW.
Endocrinology 09/2010; 151(9):4280-8. · 4.46 Impact Factor
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ABSTRACT: The onset of insulin resistance, the sites of action, and the mechanisms through which tumor necrosis factor-alpha (TNF-alpha) exacerbates the increase in adiposity and the development of insulin resistance in mice fed high-fat (HF) diet remain unclear. Here we investigated the effect of TNF-alpha deficiency on adiposity and insulin resistance during the initial 1 to 4 weeks of HF feeding. We examined body weight; the distribution of white adipose tissue (WAT); homeostasis model assessment; and levels of leptin, resistin, and adiponectin in the initial 4 weeks of HF feeding in TNF-alpha knockout (KO) mice and wild-type (WT) controls. Through 4 weeks of HF feeding, KO mice, unlike WT mice, maintained normal insulin sensitivity. Although WT-HF and KO-HF mice had similar levels of WAT at this time, KO-HF mice had more subcutaneous and less epididymal fat than WT-HF mice. The KO-HF mice also had less liver fat than the WT-HF mice. Finally, KO-HF mice had lower plasma levels of resistin than WT-HF mice. These data demonstrate that genetic lack of TNF-alpha protects insulin sensitivity during the early phase of HF feeding in the absence of altered total WAT. The data also suggest that the mechanism maintaining insulin sensitivity in the absence of TNF-alpha may involve redirection of the fat deposition to the metabolically more inert subcutaneous depot or decreases in circulating resistin and resultant decrease in liver fat deposition. The efficacy of therapeutic measures designed to counteract the effects of TNF-alpha may be increased during the early stages of obesity and insulin resistance.
Metabolism: clinical and experimental 07/2010; 59(7):1065-73. · 2.59 Impact Factor
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ABSTRACT: Intravenous and intraperitoneal (IP) administration of glucagon like peptide-1 (7-36)-amide (GLP-1) inhibits eating, but the physiological relevance of this satiating effect is not yet clear. We addressed this issue by testing the effects of the GLP-1 receptor antagonist exendin 9-39 (Ex (9-39)) on spontaneous eating and on the satiating effect of exogenous GLP-1. Adult, male Sprague-Dawley rats were equipped with chronic IP catheters and received intrameal infusions (0.2 ml/min, 2.5 min) that were remotely triggered 2-3 min after the onset of the first or the second spontaneous nocturnal meal. Infusions of 10, but not 5 or 2.5 nmol/kg body weight (BW) GLP-1 significantly reduced the size of the first spontaneous nocturnal meal compared to vehicle. The first intermeal interval, subsequent meal sizes and cumulative food intake were unchanged by 10 nmol/kg GLP-1. Infusions of 10 or 30 nmol/kg BW Ex (9-39) during the second spontaneous nocturnal meal did not affect the size of that meal and decreased rather than increased meal duration. Co-infusion of 30 nmol/kg BW Ex (9-39) prevented the satiating effect of 10 nmol/kg BW GLP-1 during the first spontaneous nocturnal meal, but again did not increase meal size by itself. That a dose of Ex (9-39) that is sufficient to block the satiating effect of exogenous GLP-1 failed to increase meal size when administered alone under comparable conditions suggests that endogenous intestinal GLP-1 is not required for the control of spontaneous meal size in rats under our conditions. The situations in which GLP-1 is of physiological relevance for satiation require further research.
Physiology & Behavior 03/2010; 100(4):291-6. · 2.87 Impact Factor
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ABSTRACT: We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.
Journal of Neuroendocrinology 03/2010; 22(6):557-63. · 3.14 Impact Factor
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Forum of nutrition 01/2010; 63:9-53.
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ABSTRACT: The physiological regulation of adiposity is supposed to depend on endocrine 'adiposity signals' that inform the brain about the mass of the adipose tissue. Basal levels of insulin and leptin are widely accepted to be adiposity signals, and amylin, ghrelin and peptide YY have been hypothesized to be. Support for these ideas comes from associations between basal hormone levels and levels of adiposity, from demonstrations of receptors for these hormones in neural circuits supposed to regulate energy homeostasis, from neuropharmacological manipulations of the hormones' actions on eating and energy expenditure, and from the effects on energy balance in animals or people bearing mutations in these endocrine signaling pathways. This chapter focuses on only the first of these four types of evidence and only on insulin and leptin. We ask whether circulating levels of either hormone indeed encodes the necessary information to act as an adiposity signal. In considering this question, we emphasize the distinction between regulation of AT mass in steady versus dynamic states. We argue that the best experimental designs for identifying potentially effective adiposity signals involve situations in which the level of adiposity is changing as the organism responds to imposed perturbations. Traditionally, this is the type of design that most convincingly supports the idea that adiposity is actively regulated. Unfortunately, there are few of such studies for any of the hypothesized endocrine adiposity signals, and the evidence that is available does not strongly support the hypotheses. Therefore, we conclude that the question of how adiposity is signaled to the brain remains an open frontier in the physiology of energy homeostasis.
Forum of nutrition 01/2010; 63:111-22.
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ABSTRACT: We characterized the accuracy, sensitivity, and reliability of computed tomographic (CT) estimates of intra-abdominal (IA) and subcutaneous (S) adipose tissue (AT) in rats and mice using the Aloka rodent CT. Here, we present the first comparisons of CT estimates of the weights of AT samples ex vivo to balance weights of the same samples, of CT estimates of AT weights in vivo to the weights of resected whole-body AT, and of CT estimates of the weights of pieces of AT inserted IA or S in vivo to the weights of the same pieces ex vivo. CT underestimated AT weight ex vivo by approximately 10%, and correction of the automated categorization of IAAT and SAT by Aloka software was required. After these adjustments, correlations (r) of CT estimates and balance weights of resected AT were > or =0.99 in rats and > or =0.92 in mice. CT was impressively sensitive: the 95% probability range of CT estimates of 10,000 mg AT inserts into rats was +/-780 mg and of 500 mg inserts into mice, +/-20 mg. Scans limited to the abdominal region correlated well (r > 0.90) with whole-body scan measures of IAAT and SAT in rats and with IAAT, but not SAT (r < 0.80), in mice. Sums of IAAT and SAT correlated well with body weight in rats (r > 0.90), but not in mice (r < 0.80). Coefficients of variance (CVs) of duplicate scans were <5%. We conclude that CT is a valid tool for studies of AT weight in rats and mice, especially when rapid throughput or longitudinal measures are desired.
Obesity 10/2009; 18(4):848-53. · 4.28 Impact Factor
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ABSTRACT: LPS, a potent activator of the innate immune system, is commonly used to investigate the acute phase response to infection, including anorexia. Serotonin 2C-receptor signaling has been shown to be involved in the mediation of LPS anorexia. Here we used the selective, potent and brain-penetrant serotonin 2C-receptor antagonist SB 242084 to identify the brain sites involved in LPS anorexia. Male Long-Evans rats received 1 ml/kg intraperitoneal injections of 0 or 0.3 mg/kg SB 242084 and intraperitoneal injections of 0 or 100 microg/kg LPS 1 h later, at dark onset. Food intake was measured in one set of rats and c-Fos immunoreactivity in another, unfed, group 90 min after LPS injection. SB 242084 markedly attenuated the LPS-induced reduction in food intake, with no anorexia evident for the first 2 h after LPS. SB 242084 also completely blocked the LPS-induced increases in c-Fos expression in the paraventricular nucleus, central nucleus of the amygdala, nucleus tractus solitarii, median raphe nucleus and dorsal raphe nucleus and partially blocked it in the A1 noradrenergic area of the ventrolateral medulla and the raphe pallidus nucleus. SB 242084 did not significantly alter the c-Fos response in the arcuate nucleus or the raphe magnus nucleus. These data indicate that 2C receptor signaling activates a diffuse neural network, presumably mediating anorexia and other responses to LPS; they also suggest that the arcuate and the raphe magnus neurons that express c-Fos after LPS are not necessary for LPS anorexia.
Brain research 09/2009; 1306:77-84. · 2.46 Impact Factor
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ABSTRACT: Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.
Brain research 03/2009; 1268:88-96. · 2.46 Impact Factor
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ABSTRACT: Isomaltulose (alpha-D-glucosylpyranosyl-1,6-D-fructofuranose) is a natural disaccharide used in human nutrition. It is structurally related to sucrose, but more slowly hydrolyzed and absorbed. Because this sugar's metabolic effects are poorly characterized, we compared the effects of chronic ad libitum access to high-isomaltulose and high-sucrose diets on glucose metabolism in rats.
Adult male rats were offered 62% isomaltulose, sucrose or starch diets ad libitum for 26 (trial 1) or 56 (trial 2) days. After 2- to 3-week adaptation, plasma glucose, fructose and insulin were measured after test meals of the adaptation diet.
The main finding was that both plasma glucose and plasma insulin concentrations were transiently but markedly increased after sucrose test meals compared to isomaltulose or starch meals. These differences were not associated with consistent differences in food intake, body weight gain or adiposity.
Chronic isomaltulose feeding has beneficial effects on postprandial glucose metabolism in comparison to sucrose feeding in rats, although the effects are modest. Further work is warranted to determine whether substitution of isomaltulose for sucrose or other sweet carbohydrates might be therapeutically useful in patients with, or at risk for, insulin resistance or type 2 diabetes mellitus.
Annals of Nutrition and Metabolism 02/2009; 54(1):75-82. · 2.26 Impact Factor
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ABSTRACT: Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2-3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain.
Endocrinology 11/2008; 150(3):1174-81. · 4.46 Impact Factor
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ABSTRACT: Central and intraperitoneal C75, an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyl-transferase-1, inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether intraperitoneal C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts nonselectively, for example by eliciting illness or aversion. Another issue relates to whether intraperitoneal C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of intraperitoneal C75 on spontaneous meal patterns and the formation of conditioned taste aversion (CTA). We also tested whether the eating inhibitory effect of intraperitoneal C75 is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). Intraperitoneal injection of 3.2 and 7.5 mg/kg of C75 significantly reduced food intake 3, 12, and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg of C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. The eating inhibitory effect of C75 was not diminished in either TVX or SDA rats. We conclude that intraperitoneal injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents.
AJP Regulatory Integrative and Comparative Physiology 10/2008; 295(3):R799-805. · 3.34 Impact Factor
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ABSTRACT: 17beta-estradiol (E2), acting via estrogen receptor (ER)-alpha, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERalpha-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 microg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of (3)H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERalpha-positive cells in the cNTS after ip injection of 4 microg/kg CCK-8. We conclude that E2, acting via ERalpha in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.
Endocrinology 05/2008; 149(4):1609-17. · 4.46 Impact Factor
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ABSTRACT: Mercaptoacetate (MA) inhibits hepatic fatty acid oxidation (FAO) and stimulates feeding in rats fed fat-rich diets. To test whether the feeding stimulation by MA depends on hepatic FAO, we compared the effects of intraperitoneally injected MA (45.6 mg/kg body weight) with saline in rats fed diets containing 18% predominately long-chain triacylglycerols (LCTs; > or =90% 16 C) or 18% medium-chain triacylglycerols (MCTs; 51% 10-12 C). We hypothesized that, because medium-chain fatty acids reach the liver and are oxidized faster than long-chain fatty acids, if MA's feeding-stimulatory effect depends on hepatic FAO, MA should stimulate feeding more in MCT-fed rats than in LCT-fed rats.
Although MA injected in mid-light phase stimulated feeding similarly in MCT- and LCT-fed rats, MA injected at light onset initially stimulated food intake (1 h) only in LCT- and not in MCT-fed rats. To investigate MA's metabolic effects during the initial hour, rats were sacrificed 30 min after light-onset injections. At this time plasma beta-hydroxybutyrate appeared to be higher in MCT- than in LCT-fed rats and to be increased by MA. In a final experiment, MA did not affect fatty acid content in liver and duodenum tissues but increased fatty acids in duodenal tissue mitochondria from 12 h-fasted rats fed chow.
In light-onset tests, adaptation to the MCT diet increased hepatic FAO but not the feeding-stimulatory effect of MA in comparison with adaptation to the LCT diet, suggesting that at this time MA does not act in the liver to stimulate feeding or that this effect is not due to FAO inhibition. Inhibition of duodenal mitochondrial FAO may be another metabolic process through which MA stimulates feeding.
Nutrition 05/2008; 24(4):360-5. · 3.03 Impact Factor
