Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 310, Issue 5, 2016, Pages G310-G322

  Hartmann, Phillipp ^a   Seebauer, Caroline T ^a   Mazagova, Magdalena ^a   Horvath, Angela ^a   Wang, Lirui ^a,b   Llorente, Cristina ^a,b   Varki, Nissi M ^a,c   Brandl, Katharina ^d   Ho, Samuel B ^a,b   Schnabl, Bernd ^a,b  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

Endotoxin; Metabolic syndrome; Microbiome; Reg3

Indexed keywords

ACYL COENZYME A OXIDASE; ACYL COENZYME A OXIDASE 1; CARBOHYDRATE; F4/80 PROTEIN; FAT; HORMONE SENSITIVE LIPASE; INSULIN; INTERLEUKIN 1BETA; INTERLEUKIN 22; KETONE BODY; MONOCYTE CHEMOTACTIC PROTEIN 1; MUCIN 2; PROTEIN; REG3B PROTEIN; REG3G PROTEIN; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; ENDOTOXIN; INTERLEUKIN DERIVATIVE; INTERLEUKIN-22; PAP PROTEIN, MOUSE; PROTECTIVE AGENT; REG3G PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; DIET INDUCED FATTY LIVER DISEASE; DIET INDUCED OBESITY; ENTERITIS; EXPERIMENTAL FATTY LIVER; FATTY ACID OXIDATION; FATTY LIVER; FEMALE; FOOD INTAKE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; INFLAMMATORY INFILTRATE; INSULIN DEFICIENCY; INSULIN RESISTANCE; INSULIN SENSITIVITY; INTESTINE ABSORPTION; LIPID DIET; LIPOLYSIS; MALABSORPTION; MALE; MITOCHONDRION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; PROTEIN FUNCTION; WEIGHT GAIN; WHITE ADIPOSE TISSUE; ADIPOSE TISSUE; ANIMAL; DEFICIENCY; DISEASE MODEL; IMMUNOLOGY; INFLAMMATION; INTESTINE FLORA; INTESTINE MUCOSA; KNOCKOUT MOUSE; LIVER; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; PATHOLOGY; REGENERATION;

ADIPOSE TISSUE; ANIMALS; DIET, HIGH-FAT; DISEASE MODELS, ANIMAL; ENDOTOXINS; GASTROINTESTINAL MICROBIOME; INFLAMMATION; INTERLEUKINS; INTESTINAL MUCOSA; LIVER; MICE; MICE, KNOCKOUT; MUCIN-2; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; PROTECTIVE AGENTS; PROTEINS; REGENERATION;

EID: 84984643530     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00094.2015     Document Type: Article

References (48)

1. Brenner DA, Paik YH, Schnabl B. Role of gut microbiota in liver disease. J Clin Gastroenterol 49, Suppl 1: S25–S27, 2015.
2. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D, Coussieu C, Basdevant A, Bar Hen A, Bedossa P, Guerre-Millo M, Clément K. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 55: 1554–1561, 2006.
3. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R. Changes in gut microbiota control metabolic endotoxemiainduced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57: 1470–1481, 2008.
4. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58: 1091–1103, 2009.
5. Chen P, Starkel P, Turner JR, Ho SB, Schnabl B. Dysbiosis-induced intestinal inflammation activates tumor necrosis factor receptor I and mediates alcoholic liver disease in mice. Hepatology 61: 883–894, 2015.
6. Chen P, Torralba M, Tan J, Embree M, Zengler K, Starkel P, van Pijkeren JP, DePew J, Loomba R, Ho SB, Bajaj JS, Mutlu EA, Keshavarzian A, Tsukamoto H, Nelson KE, Fouts DE, Schnabl B. Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice. Gastroenterology 148: 203–214.e216, 2015.
7. Collado MC, Derrien M, Isolauri E, de Vos WM, Salminen S. Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly. Appl Environ Microbiol 73: 7767–7770, 2007.
8. Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NM, Magness S, Jobin C, Lund PK. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5: e12191, 2010.
9. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 110: 9066– 9071, 2013.
10. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky JM, Saltiel AR, Downes M, Evans RM. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 21: 159–165, 2015.
11. Ganz M, Csak T, Szabo G. High fat diet feeding results in gender specific steatohepatitis and inflammasome activation. World J Gastroenterol 20: 8525–8534, 2014.
12. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 29: 415–445, 2011.
13. Guo X, Xia X, Tang R, Zhou J, Zhao H, Wang K. Development of a real-time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs. Lett Appl Microbiol 47: 367–373, 2008.
14. Hall SE, Wastney ME, Bolton TM, Braaten JT, Berman M. Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation. J Lipid Res 25: 1184–1194, 1984.
15. Hartmann P, Chen P, Wang HJ, Wang L, McCole DF, Brandl K, Starkel P, Belzer C, Hellerbrand C, Tsukamoto H, Ho SB, Schnabl B. Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice. Hepatology 58: 108–119, 2013.
16. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482: 179–185, 2012.
17. Horz HP, Vianna ME, Gomes BP, Conrads G. Evaluation of universal probes and primer sets for assessing total bacterial load in clinical samples: general implications and practical use in endodontic antimicrobial therapy. J Clin Microbiol 43: 5332–5337, 2005.
18. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95: 2409–2415, 1995.
19. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87–91, 1993.
20. Ki SH, Park O, Zheng M, Morales-Ibanez O, Kolls JK, Bataller R, Gao B. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology 52: 1291–1300, 2010.
21. Kuo SM. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr 4: 16–28, 2013.
22. Lu P, Bar-Yoseph F, Levi L, Lifshitz Y, Witte-Bouma J, de Bruijn AC, Korteland-van Male AM, van Goudoever JB, Renes IB. High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice. PLoS One 8: e65878, 2013.
23. McGuckin MA, Linden SK, Sutton P, Florin TH. Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9: 265–278, 2011.
24. McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity 41: 36–48, 2014.
25. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289: 76–79, 2003.
26. Nakanishi Y, Murashima K, Ohara H, Suzuki T, Hayashi H, Sakamoto M, Fukasawa T, Kubota H, Hosono A, Kono T, Kaminogawa S, Benno Y. Increase in terminal restriction fragments of Bacteroidetesderived 16S rRNA genes after administration of short-chain fructooligosaccharides. Appl Environ Microbiol 72: 6271–6276, 2006.
27. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA 311: 806–814, 2014.
28. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72: 219–246, 2010.
29. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18: 363–374, 2012.
30. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29: 71–109, 2011.
31. Pischon T, Nothlings U, Boeing H. Obesity and cancer. Proc Nutr Soc 67: 128–145, 2008.
32. Radaeva S, Sun R, Pan HN, Hong F, Gao B. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39: 1332–1342, 2004.
33. Rinttila T, Kassinen A, Malinen E, Krogius L, Palva A. Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. J Appl Microbiol 97: 1166–1177, 2004.
34. Sakamoto T, Takahashi N, Sawaragi Y, Naknukool S, Yu R, Goto T, Kawada T. Inflammation induced by RAW macrophages suppresses UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes. Am J Physiol Cell Physiol 304: C729–C738, 2013.
35. Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146: 1513–1524, 2014.
36. Tacke F, Gabele E, Bataille F, Schwabe RF, Hellerbrand C, Klebl F, Straub RH, Luedde T, Manns MP, Trautwein C, Brenner DA, Scholmerich J, Schnabl B. Bone morphogenetic protein 7 is elevated in patients with chronic liver disease and exerts fibrogenic effects on human hepatic stellate cells. Dig Dis Sci 52: 3404–3415, 2007.
37. Tajiri Y, Mimura K, Umeda F. High-sensitivity C-reactive protein in Japanese patients with type 2 diabetes. Obes Res 13: 1810–1816, 2005.
38. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027–1031, 2006.
39. Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K, Augenlicht L. Colorectal cancer in mice genetically deficient in the mucin Muc 2. Science 295: 1726–1729, 2002.
40. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328: 228–231, 2010.
41. Wang L, Hartmann P, Haimerl M, Bathena SP, Sjowall C, Almer S, Alnouti Y, Hofmann AF, Schnabl B. Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids. J Hepatol 60: 1259–1267, 2014.
42. Wang X, Ota N, Manzanillo P, Kates L, Zavala-Solorio J, Eidenschenk C, Zhang J, Lesch J, Lee WP, Ross J, Diehl L, van Bruggen N, Kolumam G, Ouyang W. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature 514: 237–241, 2014.
43. Wang Z, Yang L, Jiang Y, Ling ZQ, Li Z, Cheng Y, Huang H, Wang L, Pan Y, Yan X, Chen Y. High fat diet induces formation of spontaneous liposarcoma in mouse adipose tissue with overexpression of interleukin 22. PLoS One 6: e23737, 2011.
44. Wu H, Ballantyne CM. Inflammation versus host defense in obesity. Cell Metab 20: 708–709, 2014.
45. Wueest S, Rapold RA, Schumann DM, Rytka JM, Schildknecht A, Nov O, Chervonsky AV, Rudich A, Schoenle EJ, Donath MY, Konrad D. Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice. J Clin Invest 120: 191–202, 2010.
46. Xing WW, Zou MJ, Liu S, Xu T, Gao J, Wang JX, Xu DG. Hepatoprotective effects of IL-22 on fulminant hepatic failure induced by dgalactosamine and lipopolysaccharide in mice. Cytokine 56: 174–179, 2011.
47. Zarepour M, Bhullar K, Montero M, Ma C, Huang T, Velcich A, Xia L, Vallance BA. The mucin Muc2 limits pathogen burdens and epithelial barrier dysfunction during Salmonella enterica serovar Typhimurium colitis. Infect Immun 81: 3672–3683, 2013.
48. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29: 947–957, 2008.