Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages
Abstract
:1. Introduction
2. Animals and Diets
2.1. Serum Biochemical Analysis
2.2. Gut Microbiota Analysis
2.3. Cell Culture
2.4. Effects of Sphingolipids on LPS Stimulation of RAW264.7 Macrophages
2.5. RNA isolation, cDNA Synthesis, and qRT-PCR
2.6. Statistical Analysis
3. Results
3.1. Dietary Milk SM Reduces Systemic Inflammation and Tends to Lower Circulating LPS
3.2. Gut Microbiota Composition is Mostly Unaffected by 0.1% (w/w) Dietary Milk SM
3.3. Milk SM Inhibits LPS Stimulation of Macrophages
3.4. Ceramides and Sphingosine, but Not Dihydroceramides, Inhibit LPS Stimulation of Macrophages
4. Discussion
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Hotamisligil, G.S. Inflammation and metabolic disorders. Nature 2006, 444, 860–867. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007, 56, 1761–1772. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.C.; Yeh, W.C.; Ohashi, P.S. Lps/tlr4 signal transduction pathway. Cytokine 2008, 42, 145–151. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, T. Regulation of intestinal epithelial permeability by tight junctions. Cell. Mol. Life Sci. 2013, 70, 631–659. [Google Scholar] [CrossRef] [PubMed]
- Neurath, M.F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol. 2014, 14, 329–342. [Google Scholar] [CrossRef] [PubMed]
- Ghoshal, S.; Witta, J.; Zhong, J.; de Villiers, W.; Eckhardt, E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J. Lipid Res. 2009, 50, 90–97. [Google Scholar] [CrossRef] [PubMed]
- Serino, M.; Luche, E.; Gres, S.; Baylac, A.; Berge, M.; Cenac, C.; Waget, A.; Klopp, P.; Iacovoni, J.; Klopp, C.; et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 2012, 61, 543–553. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tilg, H.; Moschen, A.R.; Kaser, A. Obesity and the microbiota. Gastroenterology 2009, 136, 1476–1483. [Google Scholar] [CrossRef] [PubMed]
- Kawano, Y.; Nakae, J.; Watanabe, N.; Kikuchi, T.; Tateya, S.; Tamori, Y.; Kaneko, M.; Abe, T.; Onodera, M.; Itoh, H. Colonic pro-inflammatory macrophages cause insulin resistance in an intestinal ccl2/ccr2-dependent manner. Cell Metab. 2016, 24, 295–310. [Google Scholar] [CrossRef] [PubMed]
- Blesso, C.N. Egg phospholipids and cardiovascular health. Nutrients 2015, 7, 2731–2747. [Google Scholar] [CrossRef] [PubMed]
- Norris, G.H.; Blesso, C.N. Dietary sphingolipids: Potential for management of dyslipidemia and nonalcoholic fatty liver disease. Nutr. Rev. 2017, 75, 274–285. [Google Scholar] [CrossRef] [PubMed]
- Vesper, H.; Schmelz, E.M.; Nikolova-Karakashian, M.N.; Dillehay, D.L.; Lynch, D.V.; Merrill, A.H., Jr. Sphingolipids in food and the emerging importance of sphingolipids to nutrition. J. Nutr. 1999, 129, 1239–1250. [Google Scholar] [PubMed]
- Hannich, J.T.; Umebayashi, K.; Riezman, H. Distribution and functions of sterols and sphingolipids. Cold Spring Harb. Perspect. Biol. 2011, 3, a004762. [Google Scholar] [CrossRef] [PubMed]
- Rombaut, R.; Dewettinck, K. Properties, analysis and purification of milk polar lipids. Int. Dairy J. 2006, 16, 1362–1373. [Google Scholar] [CrossRef]
- Noh, S.K.; Koo, S.I. Egg sphingomyelin lowers the lymphatic absorption of cholesterol and alpha-tocopherol in rats. J. Nutr. 2003, 133, 3571–3576. [Google Scholar] [PubMed]
- Nyberg, L.; Duan, R.D.; Nilsson, A. A mutual inhibitory effect on absorption of sphingomyelin and cholesterol. J. Nutr. Biochem. 2000, 11, 244–249. [Google Scholar] [CrossRef]
- Duivenvoorden, I.; Voshol, P.J.; Rensen, P.C.; van Duyvenvoorde, W.; Romijn, J.A.; Emeis, J.J.; Havekes, L.M.; Nieuwenhuizen, W.F. Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis in apoe*3leiden mice. Am. J. Clin. Nutr. 2006, 84, 312–321. [Google Scholar] [PubMed]
- Noh, S.K.; Koo, S.I. Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting intestinal absorption of cholesterol and fat in rats. J. Nutr. 2004, 134, 2611–2616. [Google Scholar] [PubMed]
- Garmy, N.; Taieb, N.; Yahi, N.; Fantini, J. Interaction of cholesterol with sphingosine: Physicochemical characterization and impact on intestinal absorption. J. Lipid Res. 2005, 46, 36–45. [Google Scholar] [CrossRef] [PubMed]
- Eckhardt, E.R.; Wang, D.Q.; Donovan, J.M.; Carey, M.C. Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers. Gastroenterology 2002, 122, 948–956. [Google Scholar] [CrossRef] [PubMed]
- Chung, R.W.; Kamili, A.; Tandy, S.; Weir, J.M.; Gaire, R.; Wong, G.; Meikle, P.J.; Cohn, J.S.; Rye, K.A. Dietary sphingomyelin lowers hepatic lipid levels and inhibits intestinal cholesterol absorption in high-fat-fed mice. PLoS ONE 2013, 8, e55949. [Google Scholar] [CrossRef] [PubMed]
- Mazzei, J.C.; Zhou, H.; Brayfield, B.P.; Hontecillas, R.; Bassaganya-Riera, J.; Schmelz, E.M. Suppression of intestinal inflammation and inflammation-driven colon cancer in mice by dietary sphingomyelin: Importance of peroxisome proliferator-activated receptor gamma expression. J. Nutr. Biochem. 2011, 22, 1160–1171. [Google Scholar] [CrossRef] [PubMed]
- Fischbeck, A.; Leucht, K.; Frey-Wagner, I.; Bentz, S.; Pesch, T.; Kellermeier, S.; Krebs, M.; Fried, M.; Rogler, G.; Hausmann, M.; Humpf, H.U. Sphingomyelin induces cathepsin D-mediated apoptosis in intestinal epithelial cells and increases inflammation in DSS colitis. Gut 2011, 60, 55–65. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leucht, K.; Fischbeck, A.; Caj, M.; Liebisch, G.; Hartlieb, E.; Benes, P.; Fried, M.; Humpf, H.U.; Rogler, G.; Hausmann, M. Sphingomyelin and phosphatidylcholine contrarily affect the induction of apoptosis in intestinal epithelial cells. Mol. Nutr. Food Res. 2014, 58, 782–798. [Google Scholar] [CrossRef] [PubMed]
- Wurfel, M.M.; Wright, S.D. Lipopolysaccharide-binding protein and soluble cd14 transfer lipopolysaccharide to phospholipid bilayers: Preferential interaction with particular classes of lipid. J. Immunol. 1997, 158, 3925–3934. [Google Scholar] [PubMed]
- Parker, T.S.; Levine, D.M.; Chang, J.C.; Laxer, J.; Coffin, C.C.; Rubin, A.L. Reconstituted high-density lipoprotein neutralizes gram-negative bacterial lipopolysaccharides in human whole blood. Infect. Immun. 1995, 63, 253–258. [Google Scholar] [PubMed]
- Memon, R.A.; Holleran, W.M.; Moser, A.H.; Seki, T.; Uchida, Y.; Fuller, J.; Shigenaga, J.K.; Grunfeld, C.; Feingold, K.R. Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin. Arterioscler. Thromb. Vasc. Biol. 1998, 18, 1257–1265. [Google Scholar] [CrossRef] [PubMed]
- Norris, G.H.; Jiang, C.; Ryan, J.; Porter, C.M.; Blesso, C.N. Milk sphingomyelin improves lipid metabolism and alters gut microbiota in high fat diet-fed mice. J. Nutr. Biochem. 2016, 30, 93–101. [Google Scholar] [CrossRef] [PubMed]
- Norris, G.H.; Porter, C.M.; Jiang, C.; Millar, C.L.; Blesso, C.N. Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice. J. Nutr. Biochem. 2017, 40, 36–43. [Google Scholar] [CrossRef] [PubMed]
- Nair, A.B.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 2016, 7, 27–31. [Google Scholar] [CrossRef] [PubMed]
- Caporaso, J.G.; Lauber, C.L.; Walters, W.A.; Berg-Lyons, D.; Huntley, J.; Fierer, N.; Owens, S.M.; Betley, J.; Fraser, L.; Bauer, M.; et al. Ultra-high-throughput microbial community analysis on the illumina hiseq and miseq platforms. ISME J. 2012, 6, 1621–1624. [Google Scholar] [CrossRef] [PubMed]
- Kozich, J.J.; Westcott, S.L.; Baxter, N.T.; Highlander, S.K.; Schloss, P.D. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the miseq illumina sequencing platform. Appl. Environ. Microbiol. 2013, 79, 5112–5120. [Google Scholar] [CrossRef] [PubMed]
- Bioinformatics/mothur.batch. Available online: https://github.com/krmaas/bioinformatics/blob/master/mothur.batch (accessed on 18 July 2017).
- Quast, C.; Pruesse, E.; Yilmaz, P.; Gerken, J.; Schweer, T.; Yarza, P.; Peplies, J.; Glockner, F.O. The silva ribosomal rna gene database project: Improved data processing and web-based tools. Nucleic Acids Res. 2013, 41, D590–596. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Garrity, G.M.; Tiedje, J.M.; Cole, J.R. Naive bayesian classifier for rapid assignment of rrna sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 2007, 73, 5261–5267. [Google Scholar] [CrossRef] [PubMed]
- Hurwitz, R.; Ferlinz, K.; Sandhoff, K. The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts. Biol. Chem. Hoppe Seyler 1994, 375, 447–450. [Google Scholar] [CrossRef] [PubMed]
- De Caceres, M.; Legendre, P. Associations between species and groups of sites: Indices and statistical inference. Ecology 2009, 90, 3566–3574. [Google Scholar] [CrossRef] [PubMed]
- Alrefai, W.A.; Annaba, F.; Sarwar, Z.; Dwivedi, A.; Saksena, S.; Singla, A.; Dudeja, P.K.; Gill, R.K. Modulation of human niemann-pick c1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 292, G369–G376. [Google Scholar] [CrossRef] [PubMed]
- Baker, R.G.; Hayden, M.S.; Ghosh, S. Nf-kappab, inflammation, and metabolic disease. Cell Metab. 2011, 13, 11–22. [Google Scholar] [CrossRef] [PubMed]
- Wouters, K.; van Gorp, P.J.; Bieghs, V.; Gijbels, M.J.; Duimel, H.; Lutjohann, D.; Kerksiek, A.; van Kruchten, R.; Maeda, N.; Staels, B.; et al. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology 2008, 48, 474–486. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Qian, Y.; Fang, Q.; Zhong, P.; Li, W.; Wang, L.; Fu, W.; Zhang, Y.; Xu, Z.; Li, X.; et al. Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to tlr4 accessory protein md2. Nat. Commun. 2017, 8, 13997. [Google Scholar] [CrossRef] [PubMed]
- Cani, P.D.; Bibiloni, R.; Knauf, C.; Waget, A.; Neyrinck, A.M.; Delzenne, N.M.; Burcelin, R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008, 57, 1470–1481. [Google Scholar] [CrossRef] [PubMed]
- Ding, S.; Chi, M.M.; Scull, B.P.; Rigby, R.; Schwerbrock, N.M.; Magness, S.; Jobin, C.; Lund, P.K. High-fat diet: Bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS ONE 2010, 5, e12191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pendyala, S.; Walker, J.M.; Holt, P.R. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 2012, 142, 1100–1101. [Google Scholar] [CrossRef] [PubMed]
- Erridge, C.; Attina, T.; Spickett, C.M.; Webb, D.J. A high-fat meal induces low-grade endotoxemia: Evidence of a novel mechanism of postprandial inflammation. Am. J. Clin. Nutr. 2007, 86, 1286–1292. [Google Scholar] [PubMed]
- Zhang, Y.; Cheng, Y.; Hansen, G.H.; Niels-Christiansen, L.L.; Koentgen, F.; Ohlsson, L.; Nilsson, A.; Duan, R.D. Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: A study on enzyme knockout mice. J. Lipid Res. 2011, 52, 771–781. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Ohlsson, L.; Duan, R.D. Psyllium and fat in diets differentially affect the activities and expressions of colonic sphingomyelinases and caspase in mice. Br. J. Nutr. 2004, 91, 715–723. [Google Scholar] [CrossRef] [PubMed]
- Nagahashi, M.; Hait, N.C.; Maceyka, M.; Avni, D.; Takabe, K.; Milstien, S.; Spiegel, S. Sphingosine-1-phosphate in chronic intestinal inflammation and cancer. Adv. Biol. Regul. 2014, 54, 112–120. [Google Scholar] [CrossRef] [PubMed]
- Nilsson, Å. Role of sphingolipids in infant gut health and immunity. J. Pediatr. 2016, 173, S53–S59. [Google Scholar] [CrossRef] [PubMed]
- Murphy, E.F.; Cotter, P.D.; Healy, S.; Marques, T.M.; O’Sullivan, O.; Fouhy, F.; Clarke, S.F.; O’Toole, P.W.; Quigley, E.M.; Stanton, C.; et al. Composition and energy harvesting capacity of the gut microbiota: Relationship to diet, obesity and time in mouse models. Gut 2010, 59, 1635–1642. [Google Scholar] [CrossRef] [PubMed]
- Henao-Mejia, J.; Elinav, E.; Jin, C.; Hao, L.; Mehal, W.Z.; Strowig, T.; Thaiss, C.A.; Kau, A.L.; Eisenbarth, S.C.; Jurczak, M.J.; et al. Inflammasome-mediated dysbiosis regulates progression of nafld and obesity. Nature 2012, 482, 179–185. [Google Scholar] [CrossRef] [PubMed]
- De Minicis, S.; Rychlicki, C.; Agostinelli, L.; Saccomanno, S.; Candelaresi, C.; Trozzi, L.; Mingarelli, E.; Facinelli, B.; Magi, G.; Palmieri, C.; et al. Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice. Hepatology 2014, 59, 1738–1749. [Google Scholar] [CrossRef] [PubMed]
- Sprong, R.C.; Hulstein, M.F.; Van der Meer, R. Bactericidal activities of milk lipids. Antimicrob. Agents Chemother. 2001, 45, 1298–1301. [Google Scholar] [CrossRef] [PubMed]
- Pfeiffer, N.; Desmarchelier, C.; Blaut, M.; Daniel, H.; Haller, D.; Clavel, T. Acetatifactor muris gen. Nov., sp. Nov., a novel bacterium isolated from the intestine of an obese mouse. Arch. Microbiol. 2012, 194, 901–907. [Google Scholar] [CrossRef] [PubMed]
- Kubeck, R.; Bonet-Ripoll, C.; Hoffmann, C.; Walker, A.; Muller, V.M.; Schuppel, V.L.; Lagkouvardos, I.; Scholz, B.; Engel, K.H.; Daniel, H.; et al. Dietary fat and gut microbiota interactions determine diet-induced obesity in mice. Mol. Metab. 2016, 5, 1162–1174. [Google Scholar] [CrossRef] [PubMed]
- Zeidan, Y.H.; Pettus, B.J.; Elojeimy, S.; Taha, T.; Obeid, L.M.; Kawamori, T.; Norris, J.S.; Hannun, Y.A. Acid ceramidase but not acid sphingomyelinase is required for tumor necrosis factor-{alpha}-induced pge2 production. J. Biol. Chem. 2006, 281, 24695–24703. [Google Scholar] [CrossRef] [PubMed]
- Pfeiffer, A.; Bottcher, A.; Orso, E.; Kapinsky, M.; Nagy, P.; Bodnar, A.; Spreitzer, I.; Liebisch, G.; Drobnik, W.; Gempel, K.; et al. Lipopolysaccharide and ceramide docking to cd14 provokes ligand-specific receptor clustering in rafts. Eur. J. Immunol. 2001, 31, 3153–3164. [Google Scholar] [CrossRef]
- Grosch, S.; Schiffmann, S.; Geisslinger, G. Chain length-specific properties of ceramides. Prog. Lipid Res. 2012, 51, 50–62. [Google Scholar] [CrossRef] [PubMed]
- Bielawska, A.; Crane, H.M.; Liotta, D.; Obeid, L.M.; Hannun, Y.A. Selectivity of ceramide-mediated biology. Lack of activity of erythro-dihydroceramide. J. Biol. Chem. 1993, 268, 26226–26232. [Google Scholar] [PubMed]
- Stiban, J.; Fistere, D.; Colombini, M. Dihydroceramide hinders ceramide channel formation: Implications on apoptosis. Apoptosis 2006, 11, 773–780. [Google Scholar] [CrossRef] [PubMed]
- Stiban, J.; Perera, M. Very long chain ceramides interfere with c16-ceramide-induced channel formation: A plausible mechanism for regulating the initiation of intrinsic apoptosis. Biochim. Biophys. Acta 2015, 1848, 561–567. [Google Scholar] [CrossRef] [PubMed]
- Shabbits, J.A.; Mayer, L.D. Intracellular delivery of ceramide lipids via liposomes enhances apoptosis in vitro. Biochim. Biophys. Acta 2003, 1612, 98–106. [Google Scholar] [CrossRef]
- Jozefowski, S.; Czerkies, M.; Lukasik, A.; Bielawska, A.; Bielawski, J.; Kwiatkowska, K.; Sobota, A. Ceramide and ceramide 1-phosphate are negative regulators of tnf-alpha production induced by lipopolysaccharide. J. Immunol. 2010, 185, 6960–6973. [Google Scholar] [CrossRef] [PubMed]
- Rozenova, K.A.; Deevska, G.M.; Karakashian, A.A.; Nikolova-Karakashian, M.N. Studies on the role of acid sphingomyelinase and ceramide in the regulation of tumor necrosis factor alpha (tnfalpha)-converting enzyme activity and tnfalpha secretion in macrophages. J. Biol. Chem. 2010, 285, 21103–21113. [Google Scholar] [CrossRef] [PubMed]
Diet Component (g/kg of Diet) | High-Fat Diet | 0.1% Milk Sphingomyelin High-Fat Diet |
---|---|---|
Casein | 265 | 265 |
l-Cystine | 4 | 4 |
Corn Starch | 0 | 0 |
Maltodextrin | 0 | 0 |
Sucrose | 253.5 | 253.5 |
Lard | 310 | 309 |
Soybean Oil | 30 | 30 |
Cellulose | 64 | 64 |
Mineral Mix, AIN-93G-MX (94046) | 48 | 48 |
Vitamin Mix, AIN-93-VX (94047) | 21 | 21 |
Choline Bitartrate | 3 | 3 |
Cholesterol | 1.5 | 1.5 |
Milk Sphingomyelin | 0 | 1 |
© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Norris, G.H.; Porter, C.M.; Jiang, C.; Blesso, C.N. Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages. Beverages 2017, 3, 37. https://doi.org/10.3390/beverages3030037
Norris GH, Porter CM, Jiang C, Blesso CN. Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages. Beverages. 2017; 3(3):37. https://doi.org/10.3390/beverages3030037
Chicago/Turabian StyleNorris, Gregory H., Caitlin M. Porter, Christina Jiang, and Christopher N. Blesso. 2017. "Dietary Milk Sphingomyelin Reduces Systemic Inflammation in Diet-Induced Obese Mice and Inhibits LPS Activity in Macrophages" Beverages 3, no. 3: 37. https://doi.org/10.3390/beverages3030037