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Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice
Open accessAbstract
We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80⁺) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = -0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.
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“Increased intestinal barrier permeability is related to the metabolic dysfunction of visceral adipose tissue (Lam et al., 2012).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Lam et al., 2012
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“Oscillibacter has been found to be associated with obesity (Xu et al., 2017), and its abundance is negatively correlated with intestinal barrier function (Lam et al., 2012).”
From Akkermansia muciniphila alleviates high‐fat‐diet ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Lam et al., 2012
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MethodInfluentialA core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · cited 1×
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“The increased transcriptional expression of pro-inflammatory factors in the mesenteric fat may be a consequence of the preferential infiltration of macrophages with a pro-inflammatory phenotype [60].”
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“Parameters used to filter sequences for analysis were based upon published studies [33,34].”
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Bäckhed, F., Manchester, J. K., Semenkovich, C. F., & Gordon, J. I. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605374104 · Cited by 2,615 · cited 1×
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Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · cited 1×
“, appears to be causative. The cross-linkage between gut microbiota, metabolic dysfunction and the immune system is best illustrated in Toll-like receptor-5 knockout mice which develop spontaneous colitis, insulin resistance, hyperlipidemia and increased visceral fat deposition”
BackgroundDominant and diet-responsive groups of bacteria within the human colonic microbiota
Walker, A. W., Ince, J., Duncan, S. H., Webster, L. M., Holtrop, G., Ze, X., Brown, D., Stares, M. D., Scott, P., Bergerat, A., et al. (2011) · The ISME Journal · doi:10.1038/ismej.2010.118 · Cited by 1,632 · cited 1×
“diet-responsive in obese individuals [54] but to date little is known”
BackgroundFain, J. N., Madan, A. K., Hiler, M. L., Cheema, P. S., & Bahouth, S. W. (2004) · Endocrinology · doi:10.1210/en.2003-1336 · Cited by 1,619 · cited 1×
“in the stromal-vascular fraction of fat depots [5,6].”
BackgroundMetabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Stockman, J. (2012) · doi:10.1016/j.yped.2010.12.040 · Cited by 1,053
Creely, S. J., McTernan, P. G., Kusminski, C. M., Fisher, F. M., Da Silva, N. F., Khanolkar, M., Evans, M., Harte, A. L., & Kumar, S. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2006 · Cited by 1,043 · cited 1×
“However, the recent report of bacterial translocation into the mesenteric fat of HFD mice [63] and of elevated circulating endotoxin levels in animal models of dietinduced obesity [12] and in obese and type 2 diabetic patients related to insulin resistance [64,65] are consistent with our hypothesized role of the gut i…”
BackgroundExploring Microbial Diversity and Taxonomy Using SSU rRNA Hypervariable Tag Sequencing
Huse, S. M., Dethlefsen, L., Huber, J. A., Welch, D. B. M., Relman, D. A., & Sogin, M. L. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000255 · Cited by 1,020 · cited 1×
“Rarefaction curves at 95% sequence identity, considered to approximate genus level, showed that the rate of sampling was comparable across all samples and demonstrated sampling depth at this taxonomic resolution was comparable to previously reported studies (Figure S1) [35–37].”
ResultClaesson, M. J., O’Sullivan, Ó., Wang, Q., Nikkilä, J., Marchesi, J. R., Smidt, H., de Vos, W. M., Ross, R. P., & O’Toole, P. W. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006669 · Cited by 900 · cited 1×
“consistently detected in the microbial community of humans [52,53].”
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“Impaired gut barrier function, along with gut inflammation, have also been observed in both genetic [11] and dietary [12,13] models of obesity.”
BackgroundAmar, J., Chabo, C., Waget, A., Klopp, P., Vachoux, C., Bermúdez‐Humarán, L. G., Smirnova, N. F., Bergé, M., Sulpice, T., Lahtinen, S. J., et al. (2011) · EMBO Molecular Medicine · doi:10.1002/emmm.201100159 · Cited by 877 · cited 1×
“However, the recent report of bacterial translocation into the mesenteric fat of HFD mice [63] and of elevated circulating endotoxin levels in animal models of dietinduced obesity [12] and in obese and type 2 diabetic patients related to insulin resistance [64,65] are consistent with our hypothesized role of the gut i…”
BackgroundCawthorn, W. P., & Sethi, J. K. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.051 · Cited by 833
Ma, T., Iwamoto, G. K., Hoa, N., Akotia, V., Pedram, A., Boivin, M., & Said, H. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00173.2003 · Cited by 811 · cited 1×
“. In Caco-2 cell cultures, TNF-α reduced transepithelial resistance and ZO-1 protein expression via a NFκB-dependent pathway”
BackgroundDing, S., Chi, M. M., Scull, B. P., Rigby, R., Schwerbrock, N. M. J., Magness, S., Jobin, C., & Lund, P. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012191 · Cited by 713 · cited 1×
“In our study, and others using obesogenic diets, mice in the experimental groups had increased TNF-a mRNA expression [37] in the intestine.”
BackgroundKarczewski, J., Troost, F. J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R.-J. M., & Wells, J. M. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00327.2009 · Cited by 676 · cited 1×
“affecting their transcriptional levels [49].”
Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Hen, A. B., Bedossa, P., et al. (2006) · Diabetes · doi:10.2337/db06-0133 · Cited by 607 · cited 1×
“sensitivity of obese individuals, whereas no such relationship was observed with subcutaneous fat [7].”
BackgroundAnderson, R. C., Cookson, A. L., McNabb, W. C., Park, Z., McCann, M. J., Kelly, W. J., & Roy, N. C. (2010) · BMC Microbiology · doi:10.1186/1471-2180-10-316 · Cited by 510 · cited 1×
“not entirely clear and appears to be strain-specific [47,48].”
BackgroundGut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice
Membrez, M., Blancher, F., Jaquet, M., Bibiloni, R., Cani, P. D., Burcelin, R. G., Corthesy, I., Macé, K., & Chou, C. J. (2008) · The FASEB Journal · doi:10.1096/fj.07-102723 · Cited by 493 · cited 1×
“Finally, there is an emerging body of literature demonstrating an association between altered gut microbiota profile and obesity in humans (see [14] and [15] for a recent review) which, from pioneering work on rodents [12,16,17], appears to be causative.”
BackgroundLassenius, M. I., Pietiläinen, K. H., Kaartinen, K., Pussinen, P. J., Syrjänen, J., Forsblom, C. M., Pörsti, I. H., Rissanen, A., Kaprio, J. A., Mustonen, J. T., et al. (2011) · Diabetes Care · doi:10.2337/dc10-2197 · Cited by 428 · cited 1×
“However, the recent report of bacterial translocation into the mesenteric fat of HFD mice [63] and of elevated circulating endotoxin levels in animal models of dietinduced obesity [12] and in obese and type 2 diabetic patients related to insulin resistance [64,65] are consistent with our hypothesized role of the gut i…”
BackgroundDowd, S. E., Sun, Y., Wolcott, R. D., Domingo, A., & Carroll, J. A. (2008) · Foodborne Pathogens and Disease · doi:10.1089/fpd.2008.0107 · Cited by 427
Loss of the Tight Junction Protein ZO-1 in Dextran Sulfate Sodium Induced Colitis
Poritz, L. S., Garver, K. I., Green, C., Fitzpatrick, L. R., Ruggiero, F. M., & Koltun, W. A. (2007) · Journal of Surgical Research · doi:10.1016/j.jss.2006.07.050 · Cited by 414 · cited 1×
“In an experimental model of colitis, the progressive increase in colonic permeability is associated with a corresponding reduction in ZO-1 protein expression [38].”
BackgroundForsyth, C. B., Farhadi, A., Jakate, S. M., Tang, Y., Shaikh, M. W., & Keshavarzian, A. (2009) · Alcohol · doi:10.1016/j.alcohol.2008.12.009 · Cited by 404
Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease
Suenaert, P., Bulteel, V., Lemmens, L., Noman, M., Geypens, B. J., Assche, G. V., Geboes, K. J., Ceuppens, J. L., & Rutgeerts, P. J. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05914.x · Cited by 402 · cited 1×
“. There is also some evidence suggesting a direct effect of TNF-α on gut barrier integrity. Anti-TNF-α treatment improves gut barrier function in patients with Crohn's disease”
BackgroundYe, D., Ma, I., & Ma, T. (2006) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00318.2005 · Cited by 395 · cited 1×
“to disorganization of tight-junction proteins at the intestinal barrier [41].”
BackgroundProbiotic lactobacilli and VSL#3 induce enterocyte β‐defensin 2
Schlee, M., Harder, J., Köten, B., Stange, E., Wehkamp, J., & Fellermann, K. (2008) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2007.03587.x · Cited by 393 · cited 1×
“protection [50,51].”
Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2.
Cénac, N., Coelho, A., Nguyen, C., Compton, S., Andrade-Gordon, P., MacNaughton, W., Wallace, J., Hollenberg, M., Bunnett, N., Garcia-Villar, R., et al. (2002) · American Journal of Pathology · doi:10.1016/s0002-9440(10)64466-5 · Cited by 386 · cited 1×
“and is likely to be a consequence of the ‘leakage’ of gut luminal content. Cenac et al”
BackgroundAron‐Wisnewsky, J., Tordjman, J., Poitou, C., Darakhshan, F., Hugol, D., Basdevant, A., Aissat, A., Guerre-Millo, M., & Clément, K. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0925 · Cited by 379 · cited 1×
“F4/80 cells were quantified by counting the number of adipocytes and F4/80 cells in 10 random areas at640 magnification and the abundance of F4/80 cells was normalized to 100 adipocytes [30].”
MethodThe environment within: how gut microbiota may influence metabolism and body composition
Vrieze, A., Holleman, F., Zoetendal, E. G., de Vos, W. M., Hoekstra, J. B. L., & Nieuwdorp, M. (2010) · Diabetologia · doi:10.1007/s00125-010-1662-7 · Cited by 358 · cited 1×
“obesity and metabolic dysfunction [44].”
Youakim, A., & Ahdieh, M. (1999) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.5.g1279 · Cited by 340
Diamant, M., Blaak, E. E., & de Vos, W. M. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2010.00797.x · Cited by 308 · cited 1×
“Finally, there is an emerging body of literature demonstrating an association between altered gut microbiota profile and obesity in humans (see [14] and [15] for a recent review) which, from pioneering work on rodents [12,16,17], appears to be causative.”
BackgroundFain, J. N. (2010) · Mediators of Inflammation · doi:10.1155/2010/513948 · Cited by 301 · cited 2×
“in the stromal-vascular fraction of fat depots [5,6].”
BackgroundHolmes, J. L., Itallie, C. V. V., Rasmussen, J. E., & Anderson, J. (2006) · Gene Expression Patterns · doi:10.1016/j.modgep.2005.12.001 · Cited by 297 · cited 1×
“Primer sequences for sterol regulatory element binding protein (SREBP)-1c [23], peroxisome proliferator-activated receptor (PPAR)-c [23], proglucagon [24], zona occludens (ZO)-1 [25], occludin [26] and IL-10 [27] have been published elsewhere.”
BackgroundHighlighting new phylogenetic specificities of Crohn's disease microbiota
Mondot, S., Kang, S., Furet, J., de Cárcer, D. A., McSweeney, C., Morrison, M., Marteau, P., Doré, J., & Leclerc, M. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21436 · Cited by 283 · cited 1×
“consistently detected in the microbial community of humans [52,53].”
BackgroundKumar, P., Brooker, M. R., Dowd, S. E., & Camerlengo, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020956 · Cited by 255 · cited 1×
“Parameters used to filter sequences for analysis were based upon published studies [33,34].”
MethodAbdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus
Miyazaki, Y., Glass, L. C., Triplitt, C. L., Wajcberg, E., Mandarino, L. J., & DeFronzo, R. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.0327.2001 · Cited by 251 · cited 1×
“Visceral adiposity is strongly related to metabolic dysfunction including insulin resistance and systemic inflammation [1–3].”
BackgroundFunctional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice
Li, P., Lu, M. M., Nguyen, M. T., Bae, E. J., Chapman, J., Feng, D., Hawkins, M. A., Pessin, J. E., Sears, D. D., Nguyen, A.-K., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.100263 · Cited by 249 · cited 3×
“Serum concentrations of interleukin (IL)-1b, IL-10, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-a, IL-6, IL12p40 and plasminogen activator inhibitor (PAI)-1 were determined using commercially available cytokine kits and the xMAPH technology (Luminex Corporation, Austin, TX, USA).”
BackgroundThompson, C. L., Wang, B., & Holmes, A. J. (2008) · The ISME Journal · doi:10.1038/ismej.2008.29 · Cited by 230 · cited 1×
“5 ml of homogenate using a bead beating method as described previously [31] and stored at 220uC.”
MethodSelf-citationAdipose tissue and the immune system.
Pond, C. (2005) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2005.04.005 · Cited by 210 · cited 1×
“Equally, the presence of lymph nodes in mesenteric [61], but not epididymal, fat implies that immune cells other than macrophages, e.”
BackgroundThe obese healthy paradox: is inflammation the answer?
Barbarroja, N., López-Pedrera, C., Mayas, M. D., García‐Fuentes, E., Garrido‐Sánchez, L., Macías‐González, M., Bekay, R. E., Vidal‐Puig, A., & Tinahones, F. J. (2010) · Biochemical Journal · doi:10.1042/bj20100285 · Cited by 177 · cited 1×
“Visceral adiposity is strongly related to metabolic dysfunction including insulin resistance and systemic inflammation [1–3].”
BackgroundTerra, X., Pallarès, V., Ardèvol, A., Bladé, C., Fernández-Larrea, J., Pujadas, G., Salvadó, M. J., Arola, L., & Blay, M. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.03.006 · Cited by 171 · cited 1×
“HFD mice had increased expression of TNF-a and IL6 and macrophage infiltration in mesenteric fat [13,56] and the role of TNF-a in the systemic dysmetabolism may be particularly critical [57].”
BackgroundAkt Mediates the Effect of Insulin on Epithelial Sodium Channels by Inhibiting Nedd4-2
Lee, I., Dinudom, A., Sánchez-Pérez, Á., Kumar, S., & Cook, D. I. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701923200 · Cited by 148 · cited 1×
“Experiments were carried out under current-clamp (open-circuit) conditions as described previously [22].”
MethodSelf-citationIntestinal permeability is reduced and IL-10 levels are increased in septic IL-6 knockout mice.
Wang, Q., Fang, C.-H., & Hasselgren, P. (2001) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.2001.281.3.r1013 · Cited by 136 · cited 1×
“Assessment of gut permeability Gut permeability was measured as described by Wang et al [21] with minor modifications.”
MethodBifidobacterium exopolysaccharides fermented by human microbiota
Salazar, N., Fernández, M., Hernández-Barranco, A., Ruas-Madiedo, P., & Reyes-Gavilán, C. D. L. (2008) · Applied and Environmental Microbiology · doi:10.1128/aem.00325-08 · Cited by 134 · cited 14×
“HFD reduced Lactobacillus (75%; P,0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota.”
BackgroundInfluentialImmunomodulatory effects of Lactobacillus plantarum on human colon cancer cells
Paolillo, R., Carratelli, C. R., Sorrentino, S., Mazzola, N., & Rizzo, A. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.07.008 · Cited by 126 · cited 1×
“protection [50,51].”
Relation of Abdominal Fat Depots to Systemic Markers of Inflammation in Type 2 Diabetes
Sam, S., Haffner, S., Davidson, M., D'Agostino, R., Feinstein, S., Kondos, G., Perez, A. T., & Mazzone, T. (2009) · Diabetes Care · doi:10.2337/dc08-1856 · Cited by 120 · cited 1×
“Visceral adiposity is strongly related to metabolic dysfunction including insulin resistance and systemic inflammation [1–3].”
BackgroundZeyda, M., Gollinger, K., Kriehuber, E., Kiefer, F. W., Neuhofer, A., & Stulnig, T. M. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.103 · Cited by 114 · cited 2×
“Fluorescence data were analyzed using the Rotor-Gene 6 software (version 6.0, Qiagen). mRNA expression was normalized to RPL-19 [24], UBC [28] and 18S rRNA [29] for colon, adipose tissue and liver respectively and reported as arbitrary units.”
MethodInfluentialIntestinal, adipose, and liver inflammation in diet-induced obese mice
Li, H., Lelliott, C. J., Håkansson, P., Ploj, K., Tuneld, A., Verolin-Johansson, M., Benthem, L., Carlsson, B., Storlien, L. H., & Michaëlsson, E. (2008) · Metabolism · doi:10.1016/j.metabol.2008.07.029 · Cited by 109 · cited 2×
“HFD mice had increased expression of TNF-a and IL6 and macrophage infiltration in mesenteric fat [13,56] and the role of TNF-a in the systemic dysmetabolism may be particularly critical [57].”
BackgroundSelf-citationSachithanandan, N., Fam, B. C., Fynch, S., Dzamko, N. L., Watt, M. J., Wormald, S., Honeyman, J. E., Galić, S., Proietto, J., Andrikopoulos, S., et al. (2010) · Hepatology · doi:10.1002/hep.23861 · Cited by 107
Role of the gut in visceral fat inflammation and metabolic disorders
Lam, Y. Y., Mitchell, A. J., Holmes, A. J., Denyer, G. S., Gummesson, A., Caterson, I. D., Hunt, N. H., & Storlien, L. H. (2011) · Obesity · doi:10.1038/oby.2011.68 · Cited by 97 · cited 2×
“Taken together the case can be made, see [19], that obesogenic diets induce gut dysfunction, which may lead to the stimulation of contiguous fat by an adverse microbial load and subsequently results in visceral fat inflammation and systemic metabolic dysregulation.”
BackgroundSelf-citationObesity, visceral fat and Crohnʼs disease
Bertin, B., Desreumaux, P., & Dubuquoy, L. (2010) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32833cf0f4 · Cited by 91 · cited 1×
“an expanded mesenteric fat depot characterized by an increased infiltration of immune cells [8].”
BackgroundMast cells and histamine contribute to bile acid-stimulated secretion in the mouse colon.
Gelbmann, C. M., Schteingart, C. D., Thompson, S. M., Hofmann, A. F., & Barrett, K. E. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117988 · Cited by 74 · cited 2×
“After flushing with ice-cold bicarbonate buffer [20], segments of proximal colon (immediately below the cecum) were taken for assessment of gut permeability and gene expression (see below).”
MethodKim, O. Y., Lee, S.-M., Do, H., Moon, J., Lee, K.-H., Cha, Y., & Shin, M.-J. (2012) · Phytotherapy Research · doi:10.1002/ptr.3570 · Cited by 70
Mesenteric adipose tissue alterations resulting from experimental reactivated colitis
Gambero, A., Maróstica, M., Saad, M. A., & Pedrazzoli, J. (2007) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20222 · Cited by 65 · cited 1×
“A causal relationship between gut inflammation and mesenteric fat dysfunction (notably a relative expansion in size and an increase in expression of macrophages and immune factors) has been demonstrated in animal models of experimental colitis [9,10].”
BackgroundAntimicrobial Aspects of Inflammatory Resolution in the Mucosa: A Role for Proresolving Mediators
Campbell, E. L., Serhan, C. N., & Colgan, S. P. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100150 · Cited by 57 · cited 1×
“pro-resolving mediators that are critical in maintaining immunological homeostasis of mucosal surface [66]) and manipulation of microbiota (e.”
BackgroundProtective effect of bile acids on the onset of fructose-induced hepatic steatosis in mice
Volynets, V., Spruss, A., Kanuri, G., Wagnerberger, S., Bischoff, S. C., & Bergheim, I. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m007179 · Cited by 51 · cited 1×
“Primer sequences for sterol regulatory element binding protein (SREBP)-1c [23], peroxisome proliferator-activated receptor (PPAR)-c [23], proglucagon [24], zona occludens (ZO)-1 [25], occludin [26] and IL-10 [27] have been published elsewhere.”
BackgroundPachikian, B., Neyrinck, A., Cani, P. D., Portois, L., Deldicque, L., de Backer, F. D., Bindels, L., Sohet, F., Malaisse, W., Francaux, M., et al. (2008) · BMC Physiology · doi:10.1186/1472-6793-8-21 · Cited by 49 · cited 1×
“Primer sequences for sterol regulatory element binding protein (SREBP)-1c [23], peroxisome proliferator-activated receptor (PPAR)-c [23], proglucagon [24], zona occludens (ZO)-1 [25], occludin [26] and IL-10 [27] have been published elsewhere.”
BackgroundOliveira, M., Bosco, N., Perruisseau, G., Nicolas, J., Segura-Roggero, I., Duboux, S., Briand, M., Blum, S., & Benyacoub, J. (2011) · Clinical and Developmental Immunology · doi:10.1155/2011/807483 · Cited by 42 · cited 1×
“not entirely clear and appears to be strain-specific [47,48].”
BackgroundEffect of Lactobacillus plantarum LP‐Onlly on gut flora and colitis in interleukin‐10 knockout mice
Xia, Y., Chen, H.-Q., Zhang, M., Jiang, Y.-Q., Hang, X., & Qin, H. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2010.06498.x · Cited by 36 · cited 1×
“ameliorate gut inflammation [45] and enhance barrier function”
BackgroundNovel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet
Adapala, V. J. K., Buhman, K. K., & Ajuwon, K. M. (2011) · Journal of Inflammation · doi:10.1186/1476-9255-8-5 · Cited by 22 · cited 1×
“Similar trends of depot-specific differences in the expression of pro-inflammatory cytokines have been reported previously in animal models of high-fat feeding [58,59].”
BackgroundThomaz, M. A., Acedo, S. C., de Oliveira, C. C., Pereira, J. A., Priolli, D. G., Saad, M. J. A., Pedrazzoli, J., & Gambero, A. (2009) · Pharmacological Research · doi:10.1016/j.phrs.2009.05.003 · Cited by 20 · cited 2×
“The increased macrophage infiltration and TNF-a expression in mesenteric fat of our HFD mice is consistent with results in rats with induced gut inflammation [9] and is likely to be a consequence of the ‘leakage’ of gut luminal content.”
BackgroundResultLam, Y. Y., Janovská, A., McAinch, A. J., Belobrajdic, D. P., Hatzinikolas, G., Game, P. A., & Wittert, G. (2011) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2010.12.002 · Cited by 20 · cited 1×
“[4].”
Self-citation
Flagged first, then by citations
6 of the 72 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- R Al-Sadi, 2010, IL-1[beta]-Induced Increase in Intestinal Epithelial Tight Junction Permeability Is Mediated by MEKK-1 Activation of Canonical NF-[kappa]B Pathway., The American Journal of Pathology, 177, 2310, 10.2353/ajpath.2010.100371 · DOI
Cited by
Sorted by citations
Intestinal permeability – a new target for disease prevention and therapy
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755
“Also in peripheral blood and in adipose tissue bacteria or bacterial products can be observed following feeding with energy-rich Western style diet, an observation that might enable to define new bacterial biomarkers of intestinal barrier dysfunction in metabolic diseases [89,214].”
BackgroundAnhê, F. F., Roy, D., Pilon, G., Dudonné, S., Matamoros, S., Varin, T. V., Garofalo, C., Moine, Q., Desjardins, Y., Levy, E., et al. (2015) · Gut · doi:10.1136/gutjnl-2014-307142 · Cited by 1,137
Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota
Chang, C., Lin, C.-S., Lu, C., Martel, J., Ko, Y., Ojcius, D. M., Tseng, S., Wu, T.-R., Chen, Y. M., Young, J. D., et al. (2015) · Nature Communications · doi:10.1038/ncomms8489 · Cited by 1,254
Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance
Zhang, X., Shen, D., Fang, Z., Jie, Z., Qiu, X., Zhang, C., Chen, Y., & Ji, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071108 · Cited by 946
“It has frequently been reported that the fat and fiber content of diets can affect gut microbiota composition [22–24].”
BackgroundGut Microbiome: Profound Implications for Diet and Disease
Hills, R. D., Pontefract, B., Mishcon, H. R., Black, C. A., Sutton, S. C., & Theberge, C. R. (2022) · Kompass Nutrition & Dietetics · doi:10.1159/000523712 · Cited by 79
“Populations of Lactobacillus are reduced in alcohol consumption and in high fat diet-induced obesity [55,195].”
Background
Metadata
- Authors
- Lam, Y. Y., Ha, C. W. Y., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., & Storlien, L. H.
- Affiliations
- The University of Sydney (AU)
- Corresponding author
- Lam, Yan Y.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-23
- Volume
- 7
- Issue
- 3
- Pages
- e34233
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3311621
- OpenAlex
- W2000450805
- Cited by
- 604
- References
- 72
- Citations by year
- 2026: 24 · 2025: 33 · 2024: 39 · 2023: 58 · 2022: 62 · 2021: 59 · 2020: 58 · 2019: 53 · 2018: 44 · 2017: 41 · 2016: 41 · 2015: 34 · 2014: 29 · 2013: 21 · 2012: 8
- FWCI
- 11.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Medical Research Council
- National Health and Medical Research Council (633240)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- diet-induced obesity, high saturated fat diet, intestinal permeability, gut microbiota, mesenteric fat inflammation, visceral adipose tissue, metabolic dysfunction, tight junctions, ZO-1, TNF-α, interleukin-6, adipose tissue macrophages, Lactobacillus, Oscillibacter, adiponectin, serum amyloid A
- MeSH terms
- Animals, Diet, Female, Inflammation, Intestinal Mucosa, Intestines, Mesentery, Mice, Inbred C57BL, Permeability, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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