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1.
Objective: The aims of this study were to investigate the therapeutic potential of intestinal electrical stimulation (IES) for obesity. Experiments were performed to investigate the effects of IES on food intake, gastric tone, gastric accommodation, and its possible pathway. Research Methods and Procedures: Ten normal dogs and six dogs with truncal vagotomy were used in this study. Each dog was equipped with a gastric cannula for the measurement of gastric tone and accommodation by barostat and one pair of duodenal serosal electrodes for IES. The experiment on food intake was composed of both control session without IES and IES session after a 28‐hour fast. The experiment on gastric tone and accommodation was performed in the fasting and fed states and composed of three sessions: control, IES, and IES with NG‐nitro‐l ‐arginine. Results: IES significantly reduced food intake in the normal dogs (459.0 vs. 312.6 grams, p < 0.001). The food intake was negatively correlated with the fasting gastric volume during IES. IES significantly decreased fasting gastric tone in the normal dogs reflected as a decrease in gastric volume (89.1 vs. 261.3 mL, p < 0.01), which was abolished by vagotomy and NG‐nitro‐l ‐arginine. Discussion: IES reduces food intake and inhibits gastric tone in the fasting state. The inhibitory effect of IES on gastric tone is mediated by both vagal and nitrergic pathway.  相似文献   

2.
Duodenum electrical stimulation (DES) has been shown to delay gastric emptying and reduce food intake in dogs. The aim of this study was to investigate the effects of DES on gastric emptying, small bowel transit and food intake in pigs, a large animal model of obesity. The study consisted of three experiments (gastric emptying, small bowel transit, and food intake) in pigs implanted with internal duodenal electrodes for DES and one or two duodenal cannulas for gastric emptying and small bowel transit. We found that (i) gastric emptying was dose-dependently delayed by DES of different stimulation parameters; (ii) small bowel transit was significantly accelerated with continuous DES in proximal intestine but not with intermittent DES; (iii) DES significantly reduced body weight gain with 100% duty cycle (DC), but not with DES with 40% DC. A marginal difference was noted in food intake among 100% DC session, 40% DC session, and control session. DES with long pulses energy-dependently inhibits gastric emptying in pigs. DES with appropriate parameters accelerates proximal small bowel transit in pigs. DES reduces body weight gain in obese pigs, and this therapeutic effect on obesity is mediated by inhibiting gastric emptying and food intake, and may also possibly by accelerating intestinal transit. DES may have a potential application to treat patients with obesity.  相似文献   

3.
Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [14C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [14C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather than through a GLP-1-mediated pathway.  相似文献   

4.
Slowing of transit through the proximal small intestine by fat in the distal gut is termed the ileal brake. Intravenous naloxone, an opioid receptor antagonist, abolished the fat-induced ileal brake, suggesting that an endogenous opioid pathway may be involved in this response. To test the hypothesis that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of this response, we compared intestinal transit in dogs equipped with duodenal and midgut fistulas while naloxone was either compartmentalized with oleate to the distal half of the gut or with buffer to the proximal half of the gut. We found that intestinal transit depended on the perfusion conditions (P<0.00001). Specifically, compared with ileal brake (marker recovery of 35.7+/-7.4%), intestinal transit was accelerated when naloxone was delivered into the proximal half of the gut (76.2+/-5.2%) (P<0.005) but not the distal half of the gut (29.4+/-5.4%). We conclude that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of the ileal brake.  相似文献   

5.
The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. Eleven dogs were used for the assessment of the small intestinal contractions in both fasting and fed states. The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC) (contractile index or CI: 5.2 +/- 0.6 vs. 10.3 +/- 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 +/- 0.5 vs. 6.0 +/- 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 +/- 3.1 vs. 44.5 +/- 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time (r = -0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.  相似文献   

6.
Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high-fat diet (HFD)-induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD-induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity-related indicators. Moreover, we found that the anti-obesity effect of wild boar faecal suspension was associated with jejunal N6-methyladenosine (m6A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD-induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6A levels to achieve resistance to obesity.  相似文献   

7.
The influence was evaluated of post-weaning normal nutrition and over-nutrition upon the development of the intestinal microbiota, the alkaline phosphatase activity (AP) and occurrence of obesity in male Sprague-Dawley rats (from days 21 to 40 the control rats were submitted to ad libitum intake of a standard laboratory diet whereas overfed rats received the same diet supplemented with milk-based high fat liquid diet). The jejunal numbers of two dominant divisions of bacteria, i.e. Firmicutes (Lactobacillus/ Enterococcus — LAB) and the Bacteroidetes (Bacteroides/Prevotella — BAC), were determined using the fluorescent in situ hybridization (FISH) method, and the jejunal AP activity was assayed histochemically. On day 40, the overfed rats in comparison with control animals displayed increased adiposity accompanied by enhanced AP activity, abundance of LAB, lower amounts of BAC and, thereafter, higher LAB/BAC ratio (L/B). The numbers of LAB and L/B index positively correlated with body fat, energy intake and AP activity, whereas numbers of BAC showed an opposite tendency. These results revealed the significance of nutritional imprint upon the post-weaning development of intestinal microbial and functional axis and contribute to better understanding of their involvement in energy-balance control and in adverse and/or positive regulation of adiposity.  相似文献   

8.
Objective: To investigate the therapeutic potential of retrograde gastric electrical stimulation (RGES) for obesity in a rodent model of obesity. Research Methods and Procedures: The study was performed in 12 obese Zucker rats implanted with two pairs of gastric serosal electrodes, one pair for stimulation and the other for recording intrinsic gastric myoelectrical activity. It was composed of an acute study in three sessions to study the effect of RGES on intrinsic gastric myoelectrical activity and acute food intake and a chronic phase to study the short‐term effect of RGES on weight. RGES was performed through the distal stomach using long pulses at a frequency of tachygastria (known to induce gastric hypomotility). Results: RGES completely entrained intrinsic gastric myoelectrical activity and turned it into tachygastria at a certain strength. RGES reduced acute food intake compared with the control (p < 0.01). A 2‐week treatment of RGES resulted in a significant reduction in food intake (p = 0.002) and a significantly greater weight loss than sham stimulation (p = 0.004). Discussion: RGES at a tachygastrial frequency reduces food intake and results in weight loss in obese Zucker rats, and its effect is probably attributed to the introduction of tachygastria in the stomach.  相似文献   

9.
Chiisanoside is the main component of Acanthopanax sessiliflorus leaves. Simultaneous administration of chiisanoside resulted in a decrease in the plasma TG level and increase of undigested TG in the intestinal lumen after oil gavage to mice. This suggests that chiisanoside has the potential to prevent obesity as a lipase inhibitor which suppresses fat absorption in vivo.  相似文献   

10.
Gastric electrical stimulation (GES) has recently been explored as a therapeutic option for gastrointestinal motility disorders or obesity. The mechanism behind it is not fully elucidated. The aims of this study were to assess the effects of GES with different parameters on antral tone and to explore the involvement of the nitrergic pathway. Eight dogs equipped with a gastric cannula and one pair of serosal electrodes in the greater curvature 4 cm above the pylorus were studied on separate days. The study was composed of seven randomized sessions in the fed state [control, GES with different parameters, and GES plus neuronal nitric oxide synthase (nNOS) inhibitor]. Each session included three consecutive 30-min periods (baseline, GES, and recovery). GES was performed with long pulses or pulse trains. The antral volume was measured using an intragastric balloon connected with a barostat device. Behaviors of the dogs during each stimulation period were also noted. We found that 1) postprandial antral tone was reduced with GES with all tested parameter settings, reflected as a significant and substantial increase in antral volume ranging from 179 to 309%; 2) the inhibitory effect of GES on antral tone was partially blocked (decreased by 39.5%) with an nNOS inhibitor; and 3) mild symptoms were induced with GES and found to be correlated with the GES-induced increase in antral volume. We conclude that retrograde GES with long pulses or pulse trains inhibits antral tone, and this inhibitory effect is partially mediated via the nitrergic pathway. These results suggest that retrograde GES may have a therapeutic potential for obesity.  相似文献   

11.
Encheliophis chardewalli was described from a single cleared and stained specimen. Twelve years later, additional specimens were found in the lagoon of Moorea (French Polynesia) in association with their host, the sea cucumber Actinopyga mauritiana. These fish were used to consolidate the species diagnosis, to validate species status and to record sound production. This species is remarkable because of its ability to penetrate inside the cloaca of sea cucumbers having anal teeth and the fact this species is largely unknown despite it lives in lagoons in 1m depth. Encheliophis chardewalli produced three sound types: long regular calls made of trains of numerous pulses, short irregular calls characterized by a constant lowering of its pulse period and short regular call (or knock) made of 3 to 6 pulses. Comparison with other sympatric Carapini supports a large and distinct repertoire. Morphological characteristics could be the result of reduced body size allowing to penetrate inside a new host, thus avoiding competition and conflict with other larger sympatric Carapini species.  相似文献   

12.
This study used a digesta transfer protocol to determine the site of absorption of lysine synthesized by the gastrointestinal microflora of pigs. Eight pigs were used, four with reentrant cannulas in the terminal ileum, two with simple T cannulas in the terminal ileum, and two intact. All pigs were given, for 5 days, the same low-protein diet that included fermentable carbohydrates. The diet of two pigs with reentrant cannulas (donor) and of the two intact (control) pigs was supplemented with (15)NH(4)Cl. The two other pigs with reentrant cannulas (acceptor pigs) and those with simple cannulas (used to supply unlabeled digesta) were given the same diet but unlabeled NH(4)Cl. Ileal digesta were collected continuously from all of the reentrant cannulas and kept on ice. All digesta from each donor pig were reheated and returned to the distal cannula of its companion acceptor, whose ileal digesta were discarded. Unlabeled ileal digesta from the pigs with simple cannulas were instilled into the distal cannulas of the donor pigs. At the end of the experiment, the average (15)N enrichment in the plasma free lysine of control pigs was 0.0407 atom % excess (APE); that of donor pigs was 0.0322 APE (79% of controls), whereas that of acceptor pigs was only 0.0096 APE (24% of controls). Due to nitrogen recycling, acceptor pigs had labeled lysine in the digesta of the stomach and small intestine, and donor pigs had labeled lysine in the digesta of the large intestine. If account is taken of the higher (15)N enrichment of microbial lysine in the large compared with the small intestine, it can be estimated that >90% of the absorption of microbial lysine took place in the small intestine.  相似文献   

13.
Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1), an apical membrane cholesterol transporter of enterocytes, thereby reduces intestinal cholesterol absorption. This treatment also increases extrahepatic reverse cholesterol transport via an undefined mechanism. To explore this, we employed a trans-intestinal cholesterol efflux (TICE) assay, which directly detects circulation-to-intestinal lumen 3H-cholesterol transit in a cannulated jejunal segment, and found an increase of TICE by 45%. To examine whether such increase in efflux occurs at the intestinal brush border membrane(BBM)-level, we performed luminal perfusion assays, similar to TICE but the jejunal wall was labelled with orally-given 3H-cholesterol, and determined elevated BBM-to-lumen cholesterol efflux by 3.5-fold with ezetimibe. Such increased efflux probably promotes circulation-to-lumen cholesterol transit eventually; thus increases TICE. Next, we wondered how inhibition of NPC1L1, an influx transporter, resulted in increased efflux. When we traced orally-given 3H-cholesterol in mice, we found that lumen-to-BBM 3H-cholesterol transit was rapid and less sensitive to ezetimibe treatment. Comparison of the efflux and fractional cholesterol absorption revealed an inverse correlation, indicating the efflux as an opposite-regulatory factor for cholesterol absorption efficiency and counteracting to the naturally-occurring rapid cholesterol influx to the BBM. These suggest that the ezetimibe-stimulated increased efflux is crucial in reducing cholesterol absorption. Ezetimibe-induced increase in cholesterol efflux was approximately 2.5-fold greater in mice having endogenous ATP-binding cassette G5/G8 heterodimer, the major sterol efflux transporter of enterocytes, than the knockout counterparts, suggesting that the heterodimer confers additional rapid BBM-to-lumen cholesterol efflux in response to NPC1L1 inhibition. The observed framework for intestinal cholesterol fluxes may provide ways to modulate the flux to dispose of endogenous cholesterol efficiently for therapeutic purposes.  相似文献   

14.
Slowing of intestinal transit by fat is abolished by immunoneutralization of peptide YY (PYY), demonstrating a key role for this gut peptide. How PYY slows intestinal transit is not known. We tested the hypothesis that the slowing of intestinal transit by PYY may depend on an ondansetron-sensitive serotonergic pathway and a naloxone-sensitive opioid pathway. In a fistulated dog model, occluding Foley catheters were used to compartmentalize the small intestine into proximal (between fistulas) and distal (beyond midgut fistula) half of gut. Buffer (pH 7.0) was perfused into both proximal and distal gut, and PYY was delivered intravenously. Ondansetron or naloxone was mixed with buffer and delivered into either the proximal or distal half of gut. Intestinal transit was measured across the proximal half of the gut. The slowing of intestinal transit by PYY was abolished when either ondansetron or naloxone was delivered into the proximal, but not the distal gut, to localize the two pathways to the efferent limb of the slowing response. In addition, 5-HT slows intestinal transit with marker recovery decreased from 76.2 +/- 3.6% (control) to 33.5 +/- 2.4% (5-HT) (P < 0.0001) but was reversed by naloxone delivered into the proximal gut with marker recovery increased to 79.9 +/- 7.2% (P < 0.0005). We conclude that the slowing of intestinal transit by PYY depends on serotonergic neurotransmission via an opioid pathway.  相似文献   

15.
Sodium currents were studied under voltage clamp in the presence of neutral, amine, and quaternary local anesthetic compounds. Use-dependent block was observed as a cumulative depression of INa seen with repetitive depolarizing test pulses applied at frequencies of 2-10s-1. With quaternary QX-314, the time constant of use dependence was long, and with neutral benzocaine, very short. With lidocaine and procaine, increasing external pH (pHo) changed the time constant from long to short, but alterations of internal pH have no effect. Inactivation in Na channels was measured by the influence of prepulses on peak INa during test pulses. Single-stimulus inactivation curves were shifted more with lidocaine at high pHo than at low pHo, but inactivation curves measured during pulse trains with any of the drugs and at any pHo were strongly shifted. All measurements show that the drug-receptor reaction was slow for amine drugs at low pHo, as for quaternary drugs at any pHo, and fast for amine drugs at high pHo, as for neutral drugs at any pHo. The major effect of low pHo on amine drugs was to reduce the concentration of drugs in the fiber and to protonate drug molecules on the receptor, thus trapping them in the blocking position for a longer time. Direct effects of pH on the receptor seemed minimal.  相似文献   

16.
Nezara viridula (L.) (Pentatomidae: Heteroptera) from Brazil, Florida, Italy and Slovenia, communicate by vibratory songs associated with long‐range calling and close‐range courting, rivalry and repelling. Each song is composed of spectrally and temporally different units. Spectrally different pulses of duration less than 300 ms are present in the male calling song. The female calling song is characterized by pulse trains composed of pulses shorter than 150 ms and pulse trains composed of a longer (> 700 ms) and shorter (< 250 ms) pulse. Shorter and longer pulses have different spectral characteristics. The male and female courtship songs are characterized by fusion of shorter (< 150 ms) pulses into a pulse train usually followed by a shorter (< 200 ms) postpulse in the case of the male courtship song. The female repelling song is a several seconds long vibration of irregular temporal structure. The short (< 400 ms) male rival song pulses are frequency modulated. The dominant frequency peaks of the songs investigated lie between 70 and 130 Hz. The dominant frequency and the microstructure of song spectra show no population specificity. The average duration varies more in calling than in courtship songs. The repetition time varies extensively in songs of different populations. Normal communication followed by copulation was observed between mates from Slovenia and Brazil and between mates from Florida and Italy. The potential role of different temporal and spectral parameters for species recognition and mate location is discussed in view of the expected distortion of the characteristic signal structure during transmission through plants.  相似文献   

17.
The objective of the present experiment was to assess the involvement of small intestine in expression of susceptibility or resistance to the high-fat/high-energy diet. The investigation was carried out in adult male Sprague-Dawley rats fed either standard laboratory diet (3.2 kcal/g, 9.5 % fat) or high-fat (HF) diet (4.04 kcal/g, 30 % fat) for 4 weeks as well as in HF rats that were retrospectively designated on the bases of their higher or lower weight gain as sensitive (DIO) or resistant (DR) to obesity. Our results revealed in HF group significant increase in energy intake, food efficiency, weight gain and Lee s index of obesity. Moreover, in comparison with controls, a significantly increased duodenal and jejunal alkaline phosphatase (AP) and alpha-glucosidase activity as well as hypertrophy of jejunal mucosa (increased protein/DNA ratio) were observed in HF fed rats. In contrast, intestinal function was inversely related to energy intake or to the development of adiposity in DIO vs. DR rats. The DR rats had significantly greater AP and alpha-glucosidase activity and more pronounced suppression of energy intake than obese DIO rats. It indicates that the increase of enzyme activities and the lowered effectiveness of nutrient absorption might be a significant factor preventing the expression of obesity proneness. This information contributes to a better understanding of a complex interaction between HF diet feeding and small intestinal adaptability, which determines the energy homeostasis and predict the ability to resist or develop obesity in these phenotypes.  相似文献   

18.
Ileal resection causes malabsorption of bile acid; the increased load of bile acids in the colon induces increased secretion of salt and water and hence diarrhoea. A study was carried out to test the effect of an enterocoated cholestyramine tablet designed to disintegrate in the colon and sequester the bile acids there, thereby minimising diarrhoea induced by bile acids while having no effect on malabsorption of bile acid and jejunal fat absorption. The study comprised 14 patients who had undergone ileal resection of 40-150 cm for Crohn''s disease. A double blind crossover trial was performed with placebo and cholestyramine enterocoated with cellulose acetate phthalate. During treatment with cholestyramine the daily faecal output decreased, the number of defecations each week decreased, and the intestinal transit time increased. Acceptability of the tablets was high, in contrast with general clinical experience with cholestyramine powder. No change was observed in the total faecal output of bile acids or fat. Cholestyramine tablets caused a reduction in diarrhoea without noticeably interfering with the metabolism of fat or bile acid.  相似文献   

19.
The aim of this study was to investigate the effects and mechanisms of intestinal electrical stimulation (IES) on gastric tone, antral and pyloric contractions, and gastric emptying in dogs. Female hound dogs were equipped with a duodenal or gastric cannula, and one pair of serosal electrodes was implanted in the small intestine. The study consisted of five different experiments. Liquid gastric emptying was assessed by collection of chyme from the duodenal cannula in a number of sessions with and without IES and with and without N-nitro-l-arginine (l-NNA). Postprandial antral and pyloric contractions were measured with and without IES and in the absence and presence of l-NNA or phentolamine by placement of a manometric catheter into the antrum and pylorus via the duodenal cannula. Gastric tone was assessed by measurement of gastric volume at a constant pressure. Gastric emptying was substantially and significantly delayed by IES or l-NNA compared with the control session. IES-induced delay of gastric emptying became normal with addition of l-NNA. IES reduced gastric tone, which was blocked by l-NNA. IES also inhibited antral contractions (frequency and amplitude), and this inhibitory effect was not blocked by l-NNA but was blocked by phentolamine. IES alone did not affect pyloric tone or resistance, but IES + l-NNA decreased pyloric tone. In conclusion, IES reduces gastric tone via the nitrergic pathway, inhibits antral contractions via the adrenergic pathway, does not affect pyloric tone, and delays liquid gastric emptying. IES-induced delay of gastric emptying is attributed to its inhibitory effects on gastric motility.  相似文献   

20.
Obesity is one of the most prevalent health problems in the United States. Current therapeutic strategies for the treatment of obesity are unsatisfactory. We hypothesized the use of colon electrical stimulation (CES) to treat obesity by inhibiting upper gastrointestinal motility. In this preliminary study, we aimed at studying the effects of CES on gastric emptying of solid, intestinal motility, and food intake in dogs. Six dogs, equipped with serosal colon electrodes and a jejunal cannula, were randomly assigned to receive sham-CES or CES during the assessment of: (i) gastric emptying of solids, (ii) postprandial intestinal motility, (iii) autonomic functions, and (iv) food intake. We found that (i) CES delayed gastric emptying of solids by 77%. Guanethidine partially blocked the inhibitory effect of CES on solid gastric emptying; (ii) CES significantly reduced intestinal contractility and the effect lasted throughout the recovery period; (iii) CES decreased vagal activity in both fasting and fed states, increased the sympathovagal balance and marginally increased sympathetic activity in the fasting state; (iv) CES resulted in a reduction of 61% in food intake. CES reduces food intake in healthy dogs and the anorexigenic effect may be attributed to its inhibitory effects on gastric emptying and intestinal motility, mediated via the autonomic mechanisms. Further studies are warranted to investigate the therapeutic potential of CES for obesity.  相似文献   

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