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European Journal of Nutrition

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Open Access 01-09-2020 | Irritable Bowel Syndrome | Original Contribution

Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner

Authors: Paula Mosińska, Adrian Szczepaniak, Tatiana Wojciechowicz, Marek Skrzypski, Krzysztof Nowak, Jakub Fichna

Published in: European Journal of Nutrition | Issue 6/2020

Abstract

Purpose

We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4).

Methods

Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies.

Results

COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO.

Conclusion

Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.

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Oshima T, Miwa H (2015) Epidemiology of Functional Gastrointestinal Disorders in Japan and in the World. J Neurogastroenterol Motil 21:320–329. https://doi.org/10.5056/jnm14165 CrossRefPubMedPubMedCentral

Chey WD, Kurlander J, Eswaran S (2015) Irritable bowel syndrome: a clinical review. JAMA 313:949–958. https://doi.org/10.1001/jama.2015.0954 CrossRefPubMed

Saito YA, Schoenfeld P, Locke GR 3rd (2002) The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol 97:1910–1915. https://doi.org/10.1111/j.1572-0241.2002.05913.x CrossRefPubMed

Lovell RM, Ford AC (2012) Global prevalence of and risk factors for irritable Bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 10:712–721. https://doi.org/10.1016/j.cgh.2012.02.029 CrossRefPubMed

Palsson OS, Whitehead WE, van Tilburg MAL et al (2016) Development and validation of the Rome IV Diagnostic Questionnaire for adults. Gastroenterology 150:1481–1491. https://doi.org/10.1053/j.gastro.2016.02.014 CrossRef

Böhn L, Störsrud S, Törnblom H et al (2013) Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 108:634–641. https://doi.org/10.1038/ajg.2013.105 CrossRefPubMed

El-Salhy M, Gilja OH, Gundersen D et al (2014) Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (review). Int J Mol Med 34:363–371. https://doi.org/10.3892/ijmm.2014.1811 CrossRefPubMedPubMedCentral

El-Salhy M, Ostgaard H, Gundersen D et al (2012) The role of diet in the pathogenesis and management of irritable bowel syndrome (review). Int J Mol Med 29:723–731. https://doi.org/10.3892/ijmm.2012.926 CrossRefPubMed

De Giorgio R, Volta U, Gibson PR, Gibson P (2016) Sensitivity to wheat, gluten and FODMAPs in IBS: facts or fiction? Gut 65:169–178. https://doi.org/10.1136/gutjnl-2015-309757 CrossRefPubMed

10.

Gibson PR, Barrett JS, Muir JG (2013) Functional bowel symptoms and diet. Intern Med J 43:1067–1074. https://doi.org/10.1111/imj.12266 CrossRefPubMed

11.

Islam KBMS, Fukiya S, Hagio M et al (2011) Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141:1773–1781. https://doi.org/10.1053/j.gastro.2011.07.046 CrossRefPubMed

12.

Caldarella MP, Milano A, Laterza F et al (2005) Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant Irritable Bowel Syndrome (IBS): effect of a low-fat intraduodenal infusion. Am J Gastroenterol 100:383–389. https://doi.org/10.1111/j.1572-0241.2005.40100.x CrossRefPubMed

13.

Simrén M, Abrahamsson H, Björnsson ES (2007) Lipid-induced colonic hypersensitivity in the irritable bowel syndrome: the role of bowel habit, sex, and psychologic factors. Clin Gastroenterol Hepatol 5:201–208. https://doi.org/10.1016/j.cgh.2006.09.032 CrossRefPubMed

14.

Torres MJ, Sabate J-M, Bouchoucha M et al (2018) Food consumption and dietary intakes in 36,448 adults and their association with irritable bowel syndrome: Nutrinet-Santé study. Ther Adv Gastroenterol 11:1756283X1774662. https://doi.org/10.1177/1756283X17746625

15.

Park JH, Kwon OD, Ahn SH et al (2013) Fatty diets retarded the propulsive function of and attenuated motility in the gastrointestinal tract of rats. Nutr Res 33:228–234. https://doi.org/10.1016/j.nutres.2012.12.008 CrossRefPubMed

16.

Clarke G, Fitzgerald P, Hennessy A et al (2010) Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome. J Lipid Res 51:1186–1192. https://doi.org/10.1194/jlr.P000695 CrossRefPubMedPubMedCentral

17.

Solakivi T, Kaukinen K, Kunnas T et al (2011) Scandinavian Journal of Gastroenterology Serum fatty acid profile in subjects with irritable bowel syndrome serum fatty acid profile in subjects with irritable bowel syndrome. Scand J Gastroenterol 463:299–303. https://doi.org/10.3109/00365521.2010.533380 CrossRef

18.

Russo F, Chimienti G, Clemente C et al (2013) Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects. Scand J Gastroenterol 48:1377–1385. https://doi.org/10.3109/00365521.2013.845907 CrossRefPubMed

19.

Liu D-R, Xu X-J, Yao S-K (2018) Increased intestinal mucosal leptin levels in patients with diarrhea-predominant irritable bowel syndrome. World J Gastroenterol 24:46–57. https://doi.org/10.3748/wjg.v24.i1.46 CrossRefPubMedPubMedCentral

20.

Semnani S, Roshandel G, Keshtkar A et al (2009) Serum leptin levels and irritable Bowel syndrome. J Clin Gastroenterol 43:826–830. https://doi.org/10.1097/MCG.0b013e3181986900 CrossRefPubMed

21.

Su X, Yan H, Huang Y et al (2015) Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus. Sci Rep 21(5):18588. https://doi.org/10.1038/srep18588 CrossRef

22.

Mosińska P, Jacenik D, Sałaga M et al (2018) FABP4 blocker attenuates colonic hypomotility and modulates white adipose tissue-derived hormone levels in mouse models mimicking constipation-predominant IBS. Neurogastroenterol Motil 30:e13272. https://doi.org/10.1111/nmo.13272 CrossRefPubMed

23.

Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. J Nutr 123:1939–1951. https://doi.org/10.1093/jn/123.11.1939 CrossRefPubMed

24.

Fichna J, Sałaga M, Stuart J et al (2014) Selective inhibition of FAAH produces antidiarrheal and antinociceptive effect mediated by endocannabinoids and cannabinoid-like fatty acid amides. Neurogastroenterol Motil 26:470–481. https://doi.org/10.1111/nmo.12272 CrossRefPubMed

25.

Fichna J, Schicho R, Andrews CN et al (2009) Salvinorin A inhibits colonic transit and neurogenic ion transport in mice by activating κ-opioid and cannabinoid receptors. Neurogastroenterol Motil 21:1326-e128. https://doi.org/10.1111/j.1365-2982.2009.01369.x CrossRefPubMed

26.

Sałaga M, Polepally PR, Sobczak M et al (2014) Novel orally available salvinorin A analog PR-38 inhibits gastrointestinal motility and reduces abdominal pain in mouse models mimicking irritable bowel syndromes. J Pharmacol Exp Ther J Pharmacol Exp Ther 350:69–78. https://doi.org/10.1124/jpet.114.214239 CrossRefPubMed

27.

Fichna J, Sobczak M, Mokrowiecka A et al (2014) Activation of the endogenous nociceptin system by selective nociceptin receptor agonist SCH 221510 produces antitransit and antinociceptive effect: a novel strategy for treatment of diarrhea-predominant IBS. Neurogastroenterol Motil 26:1539–1550. https://doi.org/10.1111/nmo.12390 CrossRefPubMed

28.

Chen C, Lu M, Pan Q et al (2015) Berberine improves intestinal motility and visceral pain in the mouse models mimicking diarrhea-predominant irritable Bowel syndrome (IBS-D) symptoms in an opioid-receptor dependent manner. PLoS One 10:e0145556. https://doi.org/10.1371/journal.pone.0145556 CrossRefPubMedPubMedCentral

29.

Skrzypski M, Pruszyńska-Oszmałek E, Ruciński M et al (2012) Neuropeptide B and W regulate leptin and resistin secretion, and stimulate lipolysis in isolated rat adipocytes. Regul Pept 176:51–56. https://doi.org/10.1016/j.regpep.2012.03.004 CrossRefPubMed

30.

Chatterjee TK, Idelman G, Blanco V et al (2011) Histone deacetylase 9 is a negative regulator of adipogenic differentiation. J Biol Chem 286:27836–27847. https://doi.org/10.1074/jbc.M111.262964 CrossRefPubMedPubMedCentral

31.

Wojciechowicz T, Skrzypski M, Koodziejski PA et al (2015) Obestatin stimulates differentiation and regulates lipolysis and leptin secretion in rat preadipocytes. Mol Med Rep 12:8169–8175. https://doi.org/10.3892/mmr.2015.4470 CrossRefPubMed

32.

Skrzypski M, Kaczmarek P, Le TT et al (2012) Effects of orexin A on proliferation, survival, apoptosis and differentiation of 3T3-L1 preadipocytes into mature adipocytes. FEBS Lett 586:4157–4164. https://doi.org/10.1016/j.febslet.2012.10.013 CrossRefPubMed

33.

Włodarczyk M, Sobolewska-Włodarczyk A, Cygankiewicz AI et al (2017) G protein-coupled receptor 30 (GPR30) expression pattern in inflammatory Bowel disease patients suggests its key role in the inflammatory process. A preliminary study. J Gastrointestin Liver Dis 26:29–35. https://doi.org/10.15403/jgld.2014.1121.261.gpr CrossRefPubMed

34.

Curtis MJ, Bond RA, Spina D et al (2015) Experimental design and analysis and their reporting: new guidance for publication in BJP. Br J Pharmacol 172:3461–3471. https://doi.org/10.1111/bph.12856 CrossRefPubMedPubMedCentral

35.

Khayyatzadeh SS, Kazemi-Bajestani SMR, Mirmousavi SJ et al (2018) Dietary behaviors in relation to prevalence of irritable bowel syndrome in adolescent girls. J Gastroenterol Hepatol 33:404–410. https://doi.org/10.1111/jgh.13908 CrossRefPubMed

36.

El-Salhy M, Gundersen D (2015) Diet in irritable bowel syndrome. Nutr J 14:36. https://doi.org/10.1186/s12937-015-0022-3 CrossRefPubMedPubMedCentral

37.

Reed-Knight B, Squires M, Chitkara DK, Van Tilburg MA (2016) Adolescents with irritable bowel syndrome (IBS) report increased eating associated symptoms, changes in dietary composition, and altered eating behaviors: a pilot comparison study to healthy adolescents. Neurogastroenterol Motil 28(12):1915–1920. https://doi.org/10.1111/nmo.12894 CrossRefPubMedPubMedCentral

38.

Williams EA, Nai X, Corfe BM (2011) Dietary intakes in people with irritable bowel syndrome. BMC Gastroenterol 3(11):9. https://doi.org/10.1186/1471-230X-11-9 CrossRef

39.

Saito YA, Locke GR, Weaver AL et al (2005) Diet and functional gastrointestinal disorders: a population-based case–control study. Am J Gastroenterol 100:2743–2748. https://doi.org/10.4321/S0004-05922011000300032 CrossRefPubMed

40.

Simrén M, Månsson A, Langkilde AM et al (2001) Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 63:108–15. https://doi.org/10.1159/000051878 CrossRefPubMed

41.

Hayes P, Corish C, O’Mahony E, Quigley EMM (2014) A dietary survey of patients with irritable bowel syndrome. J Hum Nutr Diet 27:36–47. https://doi.org/10.1111/jhn.12114 CrossRefPubMed

42.

Turner N, Hariharan K, TidAng J et al (2009) Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species dependent: potent tissue-specific effects of medium-chain fatty acids. Diabetes 58:2547–2554. https://doi.org/10.2337/db09-0784 CrossRefPubMedPubMedCentral

43.

Takeuchi H, Sekine S, Kojima K, Aoyama T (2008) The application of medium-chain fatty acids: edible oil with a suppressing effect on body fat accumulation. Asia Pac J Clin Nutr 17(Suppl 1):320–323PubMed

44.

Žáček P, Bukowski M, Mehus A et al (2019) Dietary saturated fatty acid type impacts obesity-induced metabolic dysfunction and plasma lipidomic signatures in mice. J Nutr Biochem 64:32–44. https://doi.org/10.1016/j.jnutbio.2018.10.005 CrossRefPubMed

45.

Nurul-Iman BS, Kamisah Y, Jaarin K, Qodriyah HMS (2013) Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil. Evid Based Complement Altern Med 2013:629329. https://doi.org/10.1155/2013/629329 CrossRef

46.

Lee Y-Y, Tang T-K, Phuah E-T et al (2018) Structural difference of palm based medium- and long-chain triacylglycerol (MLCT) further reduces body fat accumulation in DIO C57BL/6J mice when consumed in low fat diet for a mid-term period. Food Res Int 103:200–207. https://doi.org/10.1016/j.foodres.2017.10.022 CrossRefPubMed

47.

Zhou S, Wang Y, Jiang Y et al (2017) Dietary intake of structured lipids with different contents of medium-chain fatty acids on obesity prevention in C57BL/6J mice. J Food Sci 82:1968–1977. https://doi.org/10.1111/1750-3841.13789 CrossRefPubMed

48.

DeLany JP, West DB (2000) Changes in body composition with conjugated linoleic acid. J Am Coll Nutr 19:487S–493SCrossRef

49.

West DB, Blohm FY, Truett AA, DeLany JP (2000) Conjugated linoleic acid persistently increases total energy expenditure in AKR/J mice without increasing uncoupling protein gene expression. J Nutr 130:2471–2477. https://doi.org/10.1093/jn/130.10.2471 CrossRefPubMed

50.

Park Y, Park Y (2012) Conjugated fatty acids increase energy expenditure in part by increasing voluntary movement in mice. Food Chem 133:400–409. https://doi.org/10.1016/j.foodchem.2012.01.051 CrossRefPubMed

51.

Lee S-R, Khamoui AV, Jo E et al (2017) Effect of conjugated linoleic acids and omega-3 fatty acids with or without resistance training on muscle mass in high-fat diet-fed middle-aged mice. Exp Physiol 102:1500–1512. https://doi.org/10.1113/EP086317 CrossRefPubMed

52.

Takada R, Saitoh M, Mori T (1994) Dietary γ-linolenic acid-enriched oil reduces body fat content and induces liver enzyme activities relating to fatty acid β-oxidation in rats. J Nutr 124:469–474. https://doi.org/10.1093/jn/124.4.469 CrossRefPubMed

53.

Javadi M, Everts H, Hovenier R et al (2018) The effect of six different C18 fatty acids on body fat and energy metabolism in mice. Br J Nutr 92(3):391–399. https://doi.org/10.1079/BJN20041217 CrossRef

54.

Nazari M, Saberi A, Karandish M, Jalali M (2018) Adipose tissue miRNA level variation through conjugated linoleic acid supplementation in diet-induced obese rats. Adv Clin Exp Med 27:1477–1482. https://doi.org/10.17219/acem/93728 CrossRefPubMed

55.

Uysal KT, Scheja L, Wiesbrock SM et al (2000) Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 141:3388–3396. https://doi.org/10.1210/endo.141.9.7637 CrossRefPubMed

56.

Maeda K, Cao H, Kono K et al (2005) Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 1:107–119. https://doi.org/10.1016/j.cmet.2004.12.008 CrossRefPubMed

57.

Mosińska P, Martin-Ruiz M, Gonzalez A et al (2019) Changes in the diet composition of fatty acids and fibre affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: in vivo and in vitro studies. Neurogastroenterol Motil 30:e13651. https://doi.org/10.1111/nmo.13651 CrossRef

58.

Feltrin KL, Little TJ, Meyer JH et al (2004) Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length. Am J Physiol Integr Comp Physiol 287:R524–R533. https://doi.org/10.1152/ajpregu.00039.2004 CrossRef

59.

Feltrin KL, Little TJ, Meyer JH et al (2008) Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men. Am J Clin Nutr 87(5):1181–1187. https://doi.org/10.1093/ajcn/87.5.1181 CrossRefPubMed

60.

Tadesse WT, Hailu AE, Gurmu AE, Mechesso AF (2014) Experimental assessment of antidiarrheal and antisecretory activity of 80% methanolic leaf extract of Zehneria scabra in mice. BMC Complement Altern Med 14:460. https://doi.org/10.1186/1472-6882-14-460 CrossRefPubMedPubMedCentral

61.

Accarino AM, Azpiroz F, Malagelada J-R (2002) Gut perception in humans is modulated by interacting gut stimuli. Am J Physiol Gastrointest Liver Physiol 282:220–225. https://doi.org/10.1152/ajpgi.00161.2001.-Digestive CrossRef

62.

Hammer J, Führer M (2007) Intestinal chemo- and mechano-sensitivity: selective modification of small intestinal sensitivity by lipids. Aliment Pharmacol Ther 26:117–124. https://doi.org/10.1111/j.1365-2036.2007.03352.x CrossRefPubMed

63.

Feinle-Bisset C, Azpiroz F (2013) Dietary lipids and functional gastrointestinal disorders. Am J Gastroenterol 108:737–747. https://doi.org/10.1038/ajg.2013.76 CrossRefPubMed

64.

Azain MJ (2004) Role of fatty acids in adipocyte growth and development. J Anim Sci 82:916–924. https://doi.org/10.2527/2004.823916x CrossRefPubMed

65.

Furuhashi M, Hiramitsu S, Mita T et al (2016) Reduction of circulating FABP4 level by treatment with omega-3 fatty acid ethyl esters. Lipids Health Dis 15:1–9. https://doi.org/10.1186/s12944-016-0177-8 CrossRef

66.

Prostek A, Gajewska M, Bałasińska B (2016) The influence of eicosapentaenoic acid and docosahexaenoic acid on expression of genes connected with metabolism and secretory functions of ageing 3T3–L1 adipocytes. Prostaglandins Other Lipid Mediat 125:48–56. https://doi.org/10.1016/j.prostaglandins.2016.04.002 CrossRefPubMed

67.

Rabalert J, Munkong N, Parklak W et al (2016) Effects of coconut oil on lipid accumulation in 3T3–L1 cells. Planta Med 82(S01):S1–S381. https://doi.org/10.1055/s-0036-1596845 CrossRef

68.

Satory DL, Smith SB (1999) Conjugated linoleic acid inhibits proliferation but stimulates lipid filling of murine 3T3–L1 preadipocytes. J Nutr 129:92–97. https://doi.org/10.1093/jn/129.1.92 CrossRefPubMed

69.

Li Y, Rong Y, Bao L et al (2017) Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid (SDA) in 3T3–L1 cells. Lipids Health Dis 16(1):181. https://doi.org/10.1186/s12944-017-0574-7 CrossRefPubMedPubMedCentral

Title: Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner
Authors: Paula Mosińska
Adrian Szczepaniak
Tatiana Wojciechowicz
Marek Skrzypski
Krzysztof Nowak
Jakub Fichna
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Irritable Bowel Syndrome
Diarrhea
Diarrhea
Published in: European Journal of Nutrition / Issue 6/2020
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-019-02094-2

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Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

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Methods

Results

Conclusion

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