Intra-gastric triacetin alters upper gastrointestinal motility in conscious dogs

Transcription

1 Online Submissions: doi: /wjg.v20.i World J Gstroenterol 2014 Jnury 28; 20(4): ISSN (print) ISSN (online) 2014 Bishideng Publishing Group Co., Limited. All rights reserved. BRIEF ARTICLE Intr-gstric tricetin lters upper gstrointestinl motility in conscious dogs Kzums Oosk, Mski Tokud, Nohiro Furukw Kzums Oosk, Reserch nd Development Deprtment, Fushimi Phrmceuticl Co., Ltd., Kgw , Jpn Mski Tokud, Deprtment of Cell Physiology, Fculty of Medicine, Kgw University, Kgw , Jpn Nohiro Furukw, Deprtment of Clinicl Nutrition, Fculty of Helth Science nd Technology, Kwski University of Medicl Welfre, Kurshiki , Jpn Author contributions: Oosk K nd Furukw N contributed eqully in performing the reserch, nlyzing the dt, nd writing the mnuscript; nd Tokud M contributed to the design of the reserch project. Correspondence to: Dr. Kzums Oosk, Reserch nd Development Deprtment, Fushimi Phrmceuticl Co., Ltd., Nktsu-cho 1676, Mrugme, Kgw , Jpn. ohsk@fushimi.co.jp Telephone: Fx: Received: August 31, 2013 Revised: October 30, 2013 Accepted: December 5, 2013 Published online: Jnury 28, 2014 Abstrct AIM: To exmine the effect of intr-gstric tricetin on both upper gstrointestinl motility nd proximl gstric tone in conscious dogs. METHODS: Three begle dogs under sedtion were surgiclly implnted with gstrocutneous fistul in the gstric body nd force trnsducers in the gstric ntrum nd duodenum. Beginning t week-2 fter insertion, the nimls were either fsted for 24 h or fed liquid mel 2-3 h before the experiment. With the nimls fully conscious, polyethylene bg ws inserted into the proximl stomch through the gstrocutneous fistul, followed by 15 min of ir infltion (miniml distending pressure of +2 mmhg) nd then 20 ml of low-, mid- or high-concentrtion tricetin solution (%, % nd %) or wrm wter (vehicle control). The proximl stomch receptive volume nd gstric ntrl nd duodenl contrctions were mesured over 10 min. The experiment ws repeted twice per week over severl months, with ech niml receiving t lest one infusion of the vrious tricetin solutions nd the vehicle t different times. Intergroup differences were ssessed by ANOVA nd Bonferroni-Dunn post-hoc testing. RESULTS: Intr-gstric infusion of mid- nd high-concentrtion tricetin induced n increse in the proximl stomch receptive volume, nd the verge increse induced by the high-concentrtion t 0-4 min fter infusion ws significntly greter thn tht induced by the vehicle control (62.4 ± 9.8 vs 18.4 ± 4.7, p < 1). The mid- nd high-concentrtion tricetin lso produced temporry inhibition of the gstric ntrl contrctions t 2 min fter infusions; however, only the fsted group showed tricetin-induced ntrl contrctile inhibition tht ws significntly greter thn tht in the vehicle control group (p < 5). In ddition, only the fsted group showed high-concentrtion tricetininduced increse in duodenl contrctions t 9-10 min tht ws significntly different from tht in the vehicle control group (p < 5). CONCLUSION: Intr-gstric infusion of %-% tricetin delys gstric emptying by incresing proximl stomch receptive volume, temporrily inhibiting gstric ntrl contrctions nd fcilitting duodenl contrctions Bishideng Publishing Group Co., Limited. All rights reserved. Key words: Gstrointestinl motility; Brostt; Proximl gstric relxtion; Short-chin triglycerides Core tip: Intr-gstric infusion of short-chin triglycerides, such s tricetin, hs been shown to dely gstric emptying in conscious dogs, but the influence on upper gstrointestinl motility is unknown. The current study exmined time-dependent chnges in motility following intr-gstric tricetin dministrtion t vrious doses in 1054 Jnury 28, 2014 Volume 20 Issue 4

2 Oosk K et l. Tricetin lters upper gstrointestinl motility conscious dogs nd evluted the effects of fsted vs fed stte. Compred to infusion of wter (vehicle) lone, the % nd % tricetin doses induced significnt increse in the proximl stomch receptive volume, temporry inhibition of gstric ntrl contrctions, nd n increse in the duodenl contrctions in fsted dogs. Antrum Bg Abdominl wll Infusion tube Pressure sensor Cylinder Oosk K, Tokud M, Furukw N. Intr-gstric tricetin lters upper gstrointestinl motility in conscious dogs. World J Gstroenterol 2014; 20(4): Avilble from: URL: DOI: dx.doi.org/ /wjg.v20.i Gstric fistul Force trnsducers Brostt Duodenum Figure 1 Schemtic representtion of cnine experimentl model. INTRODUCTION Tricetin is both the shortest-chin triglyceride (SCT), contining ftty cids with two crbons, nd the only triglyceride tht is soluble in wter up to 6%. Its pprovl by the Food nd Drug Administrtion s sfe humn food ingredient hs led to series of studies exmining its potentil s therpeutic gent for totl prenterl nutrition [1-6]. While these studies hve shown tht tricetin cn improve nitrogen blnce [1] nd protein metbolism [2], with lck of toxicity [3], they hve lso shown miniml effects on minerl metbolism [4,5] due to the feture of wter solubility. In n in vivo study by Lynch et l [6], wherein rts were fed diets contining tricetin to determine the effects on totl diposity, ft distribution nd body composition, tricetin ws shown to provide energy without ccumultion in the body by decresing dipocyte size. However, this field of reserch is reltively new nd further investigtions on the nutritive cpcities nd relted mechnisms of tricetin re still in progress. A number of other studies hve exmined the effects of long-chin triglycerides (LCTs) on gstrointestinl motility, demonstrting their effect of delying gstric emptying nd chrcterizing their feture of slow bsorption. Specificlly, it ws shown tht when digestive products of LCTs, such s mono- or diglycerides nd long-chin ftty cids, re present in the duodenum nd jejunum, the gstric emptying rte slows down [7,8], nd tht digestion nd bsorption of LCTs into the lymphtic system is dependent upon modifiction by bile slts. Moreover, Hunt et l [9] reported tht gstric emptying is slower for 12- to 18-crbon ftty cids thn for those composed of 2 to 10 crbons, suggesting tht gstric emptying my be regulted in mnner tht llows for optiml intestinl digestion nd bsorption of foodstuffs. The processes of digestion nd bsorption of SCTs differ gretly from those of LCTs. SCTs do not require bile slts for digestion. Their pssive diffusion from the gstrointestinl trct to the portl system hs led to specultion tht gstric emptying should not be delyed by SCTs. However, when tricetin ws directly infused into the stomchs of conscious dogs, the gstric emptying rte ws delyed remrkbly [10]. Gstric emptying of liquid is known to be fcilitted by both the proximl gstric tone nd ntrum motility, both of which my lso be influenced by the fsted/fed (postprndil) stte. To determine whether tricetin cn lter upper gstrointestinl motility during the observed dely of gstric emptying in conscious dogs brostt nd force trnsducers were pplied to fsted nd fed nimls in the study described herein, nd the effects of tricetin on upper gstrointestinl motility nd the proximl gstric tone were comprtively nlyzed. MATERIALS AND METHODS Animl preprtion All niml cre nd experimentl procedures were pproved by the Animl Reserch Committee of the Kwski Medicl School (Jpn) nd conducted in ccordnce with the Guide for the Cre nd Use of Lbortory Animls [11]. Three femle begle dogs (weight: kg; ge: 1- yers) were nesthetized with medetomidine hydrochloride (20 µg/kg, subcutneous) nd pentobrbitl sodium (25 mg/kg, intrvenous). A midline lprotomy ws performed, nd stinless steel gstrocutneous fistul (inner dimeter: 15 mm; length: 80 mm) ws inserted into the middle corpus, with the plcement ensuring exterioriztion on the left side of the bdomen. Two force trnsducers were then sewn onto the wll of the gstric ntrum nd duodenum, following the direction of the circulr muscle. The force trnsducer on the ntrum ws sutured t pproximtely 3 cm from the pyloric ring, while the force trnsducer on the duodenum ws sutured t pproximtely 5 cm distl to the pyloric ring (Figure 1). The led wires of the force trnsducers were positioned to ensure percutneous exterioriztion of the bilterl scpule lower mrgins. The nimls were llowed to recuperte for two weeks, with dily monitoring for procedure-relted complictions, before experimenttion ws initited. Experimentl procedure The fully conscious prepred nimls were evluted in either the fsting phse (fter 24 h fsting) or in the post Jnury 28, 2014 Volume 20 Issue 4

3 Oosk K et l. Tricetin lters upper gstrointestinl motility prndil phse (2-3 h fter feeding of high-clorie, highprotein liquid diet). For ech phse, the experimentl procedure ws initited by opening the gstrocutneous fistul nd spirting ny contents from the stomch; the men spirted volume from the postprndil stge ws 29 ± 2.3 ml (n = 24), with residul rtio of 11%-13%. A polyethylene bg (dimeter: cm; cpcity: ml) fitted with double-lumen polyvinyl tube ws then inserted through the gstrocutneous fistul into the proximl stomch nd slowly inflted with ml of ir to ensure proper positioning. After complete defltion of the bg, polyvinyl tube ws introduced into the stomch through the gstrocutneous fistul, to llow for infusion of tricetin solution or vehicle control (wter). The double-lumen tube nd the infusion tube were fixed with dhesive vinyl tpe. Therefter, the conscious dogs were plced in sling with their legs touching the ground so tht they were supported upright without pressure on the bdomen. The double-lumen tube ws then connected to brostt (Isobr-3; G nd J Electronics, Toronto, Cnd) nd the bg ws grdully inflted from 2 to 5 mmhg in 1 mmhg stepwise 1 min increments. The miniml distending pressure (MDP) ws determined by incresing the intr-gstric pressure to the point where volume vritions were induced by respirtory motions. In this study, bg volumes of ml were required for the respirtory motions to influence intr-gstric pressure in the dogs; therefore, the MDP ws mintined t pproximtely 3 mmhg throughout the experiment. Experimentl design This study used brostt to exmine the cute effects on fundic relxtion nd gstric ntrl nd duodenl contrctions in conscious dogs in ccordnce with the methods of Furukw et l [12]. Briefly, the intr-gstric bg ws insufflted with ir for 15 min, with the dditionl +2 mmhg bringing the MDP to 5 mmhg. After the initition of insuffltion for 5 min, 20 ml of pre-wrmed (37 ) %, 1% or 2% tricetin or wter were infused directly into the stomch over period of 30 s through n infusion tube in the gstrocutneous fistul. At the sme time s the infusions, the force trnsducers were used to continuously mesure the gstric ntrl nd duodenl contrctions. For ech niml, the experimentl procedures were performed twice per week over period of severl months. Ech niml received t lest one infusion of ech of the tricetin solutions s well vehicle before completion of the experimentl course. The totl numbers of fsting nd postprndil phse experiments were nerly identicl for ll three dogs. Sttisticl nlysis During the 15 min gstric distension performed t MDP of +2 mmhg, the intr-gstric bg volume ws clculted s the gstric tone over 1 min intervls. According to Furukw et l [12], the men vlues of three intr-gstric bg volumes t 3, 4 nd 5 min fter initition of the gstric distension were designted s the bsl volume before intr-gstric infusion of either the tricetin solutions or wter. To evlute the effect of tricetin on the proximl stomch receptive volume t constnt distending pressure, the men vlues of the 1 min intervl fter the infusion were compred with the men vlues of the bsl volume. In ddition, the differences between the bsl volume nd the volume fter the infusion were clculted t 1 min intervls, with the tricetin dt for the periods between 0-10 min compred to those of wter. The effect of tricetin on contrctility ws evluted by plotting the reltive vlues of gstrointestinl contrctility size tht were obtined t every minute intervl nd clculting the re under the curve (AUC). As per the method described by Furukw et l [12], the verge of the 1 min intervls of AUC from 3 to 5 min fter the onset of distension ws used s the control vlue. The chnges in reltive mgnitudes of the contrctions from the control vlues fter the infusion were then compred between the tricetin nd wter dministrtions. These results were expressed s men ± SE The significnce of intergroup differences ws ssessed by ANOVA with Bonferroni-Dunn post-hoc testing. RESULTS Effects of intr-gstric tricetin on proximl gstric tone Fsting phse: A slight increse ws observed in the intr-gstric bg volume immeditely fter the infusion of wter, but ws not significntly different from the preinfusion volume (Figure 2A). Infusion of % tricetin did not produce significnt increse in the receptive volume, nd only slight distention of the intr-gstric bg ws observed tht ws similr to tht seen for the wter infusion (dt not shown). In contrst, infusion of % tricetin led to rpid increse in the intr-gstric bg men volume, from the men bsl volume of ± 10.2 ml to pek of ± 14.5 ml t 1 min (n = 8). In ddition, infusion of % tricetin led to similr rpid increse, from the men bsl volume of ± 7.2 ml to ± 16.2 ml t 1 min (n = 7) nd pek of ± 14.1 ml t 2 min (n = 7). These increses in the receptive volume induced by 1% nd 2% tricetin infusions were significntly greter thn the wter infusion (Figure 2A). Postprndil phse: In the postprndil phse, slight increse in the receptive volume ws observed tht ws similr to tht seen during the fsting phse. Infusions of % nd % tricetin led to rpid increses in the receptive volume, which were greter thn those induced by the wter infusion but the differences did not rech sttisticl significnce (Figure 2B). Time-relted effects of intr-gstric tricetin on proximl gstric tone Fsting phse: At 0-2 min fter infusion of % tricetin, the increse in the receptive volume (56.5 ± 10.1, 1056 Jnury 28, 2014 Volume 20 Issue 4

4 Oosk K et l. Tricetin lters upper gstrointestinl motility A Intr-gstric bg volume (ml) c c Fsting phse Wter ( n = 12) 1% tricetin (n = 8) 2% tricetin (n = 7) B Intr-gstric bg volume (ml) Postprndil phse Wter ( n = 13) 1% tricetin (n = 8) 2% tricetin (n = 7) Time fter the inter-gstric infusion of the solutions (min) Time fter the inter-gstric infusion of the solutions (min) C Chnge of intr-gstric bg volume (ml) d b d d Fsting phse Wter ( n = 12) 1% tricetin (n = 8) 2% tricetin (n = 7) d Time fter the inter-gstric infusion of the solutions (min) D Chnge of intr-gstric bg volume (ml) Postprndil phse Wter ( n = 13) 1% tricetin (n = 8) 2% tricetin (n = 7) Time fter the inter-gstric infusion of the solutions (min) Figure 2 Effect of tricetin on the proximl gstric tone in fsting nd postprndil phses. The receptive volume (representtive of gstric tone) before nd fter infusion in fsted (A, C) nd fed (B, D) nimls is presented. Dt re expressed s men ± SE (A, B) P < 5 for 1% tricetin, c P < 5 for 2% tricetin vs before infusion. (C, D) P < 5, b P < 1 for 1% tricetin vs wter; c P < 5, d P < 1 for 2% tricetin vs wter. The point of infusion is indicted by n rrow. n = 8) ws significntly greter thn tht induced by the infusion of wter lone (24.4 ± 3.7, n = 12). At 0-4 min fter infusion of % tricetin, the increse in the receptive volume (62.4 ± 9.8, n = 7) ws significntly greter thn tht induced by the infusion of wter lone (18.4 ± 4.7, n = 12) (Figure 2C). Postprndil phse: During the postprndil phse, the increses in the receptive volume induced by tricetin were lso lrger thn those induced by wter lone but the differences did not rech sttisticl significnce (Figure 2D). Effects of tricetin on gstric ntrl nd duodenl contrctions Infusion of wter lone produced no obvious chnges in the gstric ntrl contrctions, in neither the fsting nd postprndil phses (Figure 3). In contrst, both % nd % tricetin induced temporry inhibition of the gstric ntrl contrctions t 2 min fter the infusion. Only the tricetin-induced inhibition in the fsting phse ws significntly different from the contrctions observed with the wter infusion. However, fter the 2 min time point, there ws tendency for fcilittion of the gstric ntrl contrctions only for the % tricetin in both the fsting nd postprndil phses but the differences from the wterrelted contrctions did not rech sttisticl significnce. At 1-4 min fter the wter infusion, temporry fcilittion of the duodenl contrctions ws observed in both the fsting nd postprndil phses (Figure 4). For ll time points therefter, wter induced only inhibition of the duodenl contrctions. In contrst, infusion of % nd % tricetin inhibited the duodenl contrctions for nerly the entire 10-min mesurement period in both phses, with the exception of % tricetin inducing significnt increse (vs wter lone) in duodenl contrctions t 9-10 min fter the infusion. DISCUSSION The current study demonstrted tht direct infusion of tricetin into the stomch of conscious dogs lters upper gstrointestinl motility. Proximl gstric volume ws lso incresed by the infusion, which reflects stimultion of gstric relxtion. Finlly, the tricetin ws shown to inhibit gstric ntrl contrctions but induce duodenl contrctions. Induction of gstric relxtion of the proximl stomch involves two mechnisms. First, gstric relxtion is stimulted by intr-gstric filling (possibly by expnsion of the gstric wll [13] ), regrdless of the substnce involved (solids or liquids). This process is referred to s gstric ccommodtion nd is responsible for n incresed volume tolernce without perception but my lso contribute to mintining stition signls t cceptble volume lods. Second, physicl (e.g., osmotic pressure) nd chemicl (e.g., H +, lipids) prmeters of the stomch nd duodenum environments cn enhnce gstric relxtion vi fctors relted to the nervous system or hormonl xes [14,15]. In the current study, tricetin did not pper to influence osmotic pressure, since the %, % nd % tricetin ws dministered s hypotonic solutions. Moreover, the 20 ml volume tht ws infused 1057 Jnury 28, 2014 Volume 20 Issue 4

5 Oosk K et l. Tricetin lters upper gstrointestinl motility A Wter (n = 10) B Wter (n = 12) % tricetin (n = 6) % tricetin (n = 6) % tricetin (n = 6) - c % tricetin (n = 6) - Figure 3 Effects of tricetin on gstric ntrl contrctions in fsting nd postprndil phses. The ntrl contrctions recorded t every 1 min fter infusion in (A) fsted nd (B) fed nimls re presented s the reltive mgnitudes of chnge from the verge vlues t 3 min before infusion. Dt re expressed s men ± SE P < 5 for 1% tricetin vs wter, c P < 5 for 2% tricetin vs wter. into the stomch ws not expected to cuse expnsion of the gstric wll. The tricetin infusion nd subsequent bsorption in the stomch nd duodenum ppered to primrily ffect upper gstrointestinl motility. However, the observtion of duodenl fcilittion occurring immeditely fter the infusion of tricetin suggests tht the bsorption-relted process plys smller role thn tricetin s chemicl stimultion of the gstric nd duodenl mucos to cuses the gstric relxtion. Gstric ntrum nd duodenum contrctions hve distinctive mechnisms nd ptterns. For exmple, LCTmedited effects on contrctility re region specific. Prticulr LCTs cpble of inhibiting ntrl contrctility [16] hve lso been shown to fcilitte stimultion of contrctions in segments of the upper duodenum [17]. In the current study, the tricetin infusion first led to inhibition of gstric ntrl contrctions, which ws followed by n increse t lter time points of the infusion. Moreover, the infusion ppered to fcilitte duodenl contrctility. Since there ws only short period of inhibition of the ntrl contrctions, it remins uncler whether this inhibition ws responsible for cusing the dely of gstric emptying. However, such modultions of the gstric ntrum nd duodenum re expected to induce the closing of the pylorus, which my be the ultimte cuse of the delyed gstric emptying. With regrd to the observed diphsic ltertions (i.e., inhibition nd fcilittion) in the gstric ntrum, the initil inhibition my be induced by stimultion of gstric ntrl mucos, while the subsequent fcilittion my be induced by stimultion of the duodenl mucos. LCTs re known to stimulte relese of the hormone cholecystokinin (CCK), which cts to reduce proximl gstric tone [18] nd inhibit gstric emptying [19] vi ctivtion of the CCK receptors on the vgl fferent nerves. In turn, the inhibitory vgl fferents in the brinstem re ctivted [20]. SCTs, on the other hnd, produce very little 1058 Jnury 28, 2014 Volume 20 Issue 4

6 Oosk K et l. Tricetin lters upper gstrointestinl motility A - - Wter (n = 10) - B Wter (n = 12) - - 1% tricetin (n = 6) - 1% tricetin (n = 6) 2% tricetin (n = 6) - 2% tricetin (n = 6) - Figure 4 Effects of tricetin on duodenl contrctions in fsting nd postprndil phses. The duodenl contrctions recorded t every 1 min fter infusion in (A) fsted nd (B) fed nimls re presented s the reltive mgnitudes of chnge from the verge vlues t 3 min before infusion. Dt re expressed s men ± SE P < 5 for 2% tricetin vs wter. to no effects on CCK relese [21]. Therefore, the mechnism of effect for tricetin, SCT, my differ from tht of the LCTs. In the current study, the effects of tricetin relted to fsting nd fed sttes were lso exmined. While the results were lrgely similr for both the fsted nd postprndil phses, sttisticlly significnt differences were only observed in the fsted nimls. It is possible tht the up-regulted hormonl fctors tht occur during the postprndil phse my hve interfered with the tricetin, msking the effects. In conclusion, our current results indicte tht tricetin rpidly induces temporry relxtion in the proximl stomch tht is followed by contrction in both the gstric ntrum nd duodenum. This mechnism of tricetin my differ from tht of LCTs, but further investigtions re needed to confirm this distinction. COMMENTS Bckground Gstric emptying is djusted very precisely by gstrointestinl motility, so it is very importnt to exmine the chnge of gstrointestinl motility fter dministrted the dietry ingredient. The uthors reported preliminrily tht n infusion of tricetin, which is expected s new nutritionl ingredient, into the stomch delyed the gstric emptying rte in conscious dogs. However, it is still uncler whether tricetin cn chnge upper gstrointestinl motility during dely of gstric emptying. Reserch frontiers Tricetin hs been generlly recognized by the Food nd Drug Administrtion s being sfe humn food ingredient. In the re of gstrointestinl motility with tricetin, the reserch hotspot is the chnge on the proximl gstric tone nd the upper gstrointestinl motility. Innovtions nd brekthroughs In this study, to reserch the effect of tricetin on the gstric tone of the proximl stomch in conscious dogs, the uthors used polyethylene bg to mesure the receptive volume of the proximl stomch t constnt pressure before nd fter the intr-gstric infusion of tricetin. Moreover, to determine the effect 1059 Jnury 28, 2014 Volume 20 Issue 4

7 Oosk K et l. Tricetin lters upper gstrointestinl motility of tricetin on the upper gstrointestinl contrctile ctivities, the uthors used force trnsducers to mesure the gstric ntrl nd duodenl contrctions. The nimls were either fsted for 24 h or fed liquid mel 2-3 h before the experiment. Tricetin rpidly induces temporry relxtion in the proximl stomch tht is followed by contrction in both the gstric ntrum nd duodenum. The effect of tricetin ws lrgely similr for both the fsted nd postprndil phses, sttisticlly significnt differences were only observed in fsted nimls. Applictions Intr-gstric infusion of %-% tricetin delys gstric emptying by incresing proximl stomch receptive volume, temporrily inhibiting gstric ntrl contrctions nd fcilitting duodenl contrctions. Peer review This mnuscript reports novel informtion on the effect of short-chin triglycerides on gstric emptying in conscious dogs. The Authors demonstrte convincingly tht Intr-gstric infusion of %-% tricetin induced n increse of the receptive volume of the proximl stomch, nd cused temporry inhibition of the gstric ntrl contrctility, which re suggestive of retrdtion of gstric emptying. REFERENCES 1 Biley JW, Brker RL, Krlstd MD. Totl prenterl nutrition with short- nd long-chin triglycerides: tricetin improves nitrogen blnce in rts. J Nutr 1992; 122: [PMID: ] 2 Biley JW, Miles JM, Hymond MW. Effect of prenterl dministrtion of short-chin triglycerides on leucine metbolism. Am J Clin Nutr 1993; 58: [PMID: ] 3 Biley JW, Hymond MW, Miles JM. Tricetin: potentil prenterl nutrient. JPEN J Prenter Enterl Nutr 1991; 15: [PMID: DOI: / ] 4 Bleiberg B, Beers TR, Persson M, Miles JM. Metbolism of tricetin-derived cette in dogs. Am J Clin Nutr 1993; 58: [PMID: ] 5 Biley JW, Heth H, Miles JM. Clcium, mgnesium, nd phosphorus metbolism in dogs given intrvenous tricetin. Am J Clin Nutr 1989; 49: [PMID: ] 6 Lynch JW, Biley JW. Dietry intke of the short-chin triglyceride tricetin vs. long-chin triglycerides decreses dipocyte dimeter nd ft deposition in rts. J Nutr 1995; 125: [PMID: ] 7 Hunt JN. Mechnisms nd disorders of gstric emptying. Annu Rev Med 1983; 34: [PMID: DOI: /nnurev.me ] 8 Houghton LA, Mngnll YF, Red NW. Effect of incorporting ft into liquid test mel on the reltion between intrgstric distribution nd gstric emptying in humn volunteers. Gut 1990; 31: [PMID: ] 9 Hunt JN, Knox MT. A reltion between the chin length of ftty cids nd the slowing of gstric emptying. J Physiol 1968; 194: [PMID: ] 10 Oosk K. Effect of tricetin of gstric emptying. J Smooth Muscle Res (Jpn Section) 2005; 9: [DOI: /heik tsukinzshi j67] 11 Ntionl Reserch Council (US) Committee for the updte of the guide for the cre nd use of lbortory nimls. Guide for the cre nd use of lbortory nimls. 8th ed. Wshington (DC): Ntionl Acdemies Press (US), 2011: Furukw N, Mnbe N, Kse Y, Httori T, Immur H, Kusunoki H, Hrum K. Intrgstric infusion of rikkunshito (kmpo) induces proximl stomch relxtion in conscious dogs. Auton Neurosci 2013; 179: [PMID: DOI: /j.utneu ] 13 Distrutti E, Azpiroz F, Soldevill A, Mlgeld JR. Gstric wll tension determines perception of gstric distention. Gstroenterology 1999; 116: [PMID: DOI: /S (99)7006-5] 14 Jhnberg T, Abrhmsson H, Jnsson G, Mrtinson J. Gstric relxtory response to feeding before nd fter vgotomy. Scnd J Gstroenterol 1977; 12: [PMID: ] 15 Brber R, Percchi M, Brighenti F, Cesn B, Binchi PA, Bsilisco G. Senstions induced by medium nd long chin triglycerides: role of gstric tone nd hormones. Gut 2000; 46: [PMID: DOI: /gut ] 16 Heddle R, Dent J, Red NW, Houghton LA, Toouli J, Horowitz M, Mddern GJ, Downton J. Antropyloroduodenl motor responses to intrduodenl lipid infusion in helthy volunteers. Am J Physiol 1988; 254: G671-G679 [PMID: ] 17 Normn WW. Gstric emptying. In: Leonrd RJ, eds. Gstrointestinl Physiology, 6th edn. St. Louis: Mosby, Inc, 2001: Feinle C, D Amto M, Red NW. Cholecystokinin-A receptors modulte gstric sensory nd motor responses to gstric distension nd duodenl lipid. Gstroenterology 1996; 110: [PMID: DOI: /gst.1996.v110. pm ] 19 Liddle RA, Morit ET, Conrd CK, Willims JA. Regultion of gstric emptying in humns by cholecystokinin. J Clin Invest 1986; 77: [PMID: DOI: / JCI112401] 20 Zrbin MA, Wmsley JK, Innis RB, Kuhr MJ. Cholecystokinin receptors: presence nd xonl flow in the rt vgus nerve. Life Sci 1981; 29: [PMID: DOI: / (81) ] 21 Ledeboer M, Msclee AA, Biemond I, Lmers CB. Effect of medium- nd long-chin triglycerides on lower esophgel sphincter pressure: role of CCK. Am J Physiol 1998; 274: G1160-G1165 [PMID: ] P- Reviewers: Frncesco L, Izzo AA, Iwski Y S- Editor: M YJ L- Editor: A E- Editor: Wng CH 1060 Jnury 28, 2014 Volume 20 Issue 4

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