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Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity

  • Lars-Georg Hersoug (a1), Peter Møller (a1) and Steffen Loft (a1)

Abstract

It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.

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Corresponding author

*Corresponding author: Dr Lars-Georg Hersoug, fax +45 35 32 76 29, email hersoug@sund.ku.dk

References

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1. Masters, RK, Reither, EN, Powers, DA, et al. (2013) The impact of obesity on US mortality levels: the importance of age and cohort factors in population estimates. Am J Public Health 103, 18951901.
2. World Health Organization (2014) Global status report on non-communicable diseases 2014. http://apps.who.int/iris/bitstream/10665/148114/1/9789241564854_eng.pdf?ua=1 (accessed December 2017).
3. Holtcamp, W (2012) Obesogens: an environmental link to obesity. Environ Health Perspect 120, a62a68.
4. Kant, AK & Graubard, BI (2013) Family income and education were related with 30-year time trends in dietary and meal behaviors of American children and adolescents. J Nutr 143, 690700.
5. van Vliet-Ostaptchouk, JV, Snieder, H & Lagou, V (2012) Gene–lifestyle interactions in obesity. Curr Nutr Rep 1, 184196.
6. Weisberg, SP, McCann, D, Desai, M, et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112, 17961808.
7. You, T, Yang, R, Lyles, MF, et al. (2005) Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors. Am J Physiol Endocrinol Metab 288, E741E747.
8. Xu, H, Barnes, GT, Yang, Q, et al. (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112, 18211830.
9. Gualillo, O (2010) Mediators of inflammation in obesity and its comorbidities. Mediators Inflamm 2010, 239126.
10. Kahn, SE, Hull, RL & Utzschneider, KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840846.
11. Khandekar, MJ, Cohen, P & Spiegelman, BM (2011) Molecular mechanisms of cancer development in obesity. Nat Rev Cancer 11, 886895.
12. Masuoka, HC & Chalasani, N (2013) Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann N Y Acad Sci 1281, 106122.
13. Rask-Madsen, C & Kahn, CR (2012) Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler Thromb Vasc Biol 32, 20522059.
14. Giordano, A, Murano, I, Mondini, E, et al. (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54, 24232436.
15. Peyrin-Biroulet, L, Chamaillard, M, Gonzalez, F, et al. (2007) Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander? Gut 56, 577583.
16. Zhang, LJ, Guerrero-Juarez, CF, Hata, T, et al. (2015) Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 347, 6771.
17. Hersoug, LG, Moller, P & Loft, S (2016) Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity. Obes Rev 17, 297312.
18. Caesar, R, Tremaroli, V, Kovatcheva-Datchary, P, et al. (2015) Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab 22, 658668.
19. Chakraborti, CK (2015) New-found link between microbiota and obesity. World J Gastrointest Pathophysiol 6, 110119.
20. Galic, S, Oakhill, JS & Steinberg, GR (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316, 129139.
21. Divoux, A & Clement, K (2011) Architecture and the extracellular matrix: the still unappreciated components of the adipose tissue. Obes Rev 12, e494e503.
22. Khan, T, Muise, ES, Iyengar, P, et al. (2009) Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 29, 15751591.
23. Arner, P (2005) Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Metab 19, 471482.
24. Weyer, C, Foley, JE, Bogardus, C, et al. (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43, 14981506.
25. Lundgren, M, Svensson, M, Lindmark, S, et al. (2007) Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia 50, 625633.
26. Krotkiewski, M, Bjorntorp, P, Sjostrom, L, et al. (1983) Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 72, 11501162.
27. Arner, E, Westermark, PO, Spalding, KL, et al. (2010) Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59, 105109.
28. Gao, H, Mejhert, N, Fretz, JA, et al. (2014) Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue. Cell Metab 19, 981992.
29. Lessard, J, Laforest, S, Pelletier, M, et al. (2014) Low abdominal subcutaneous preadipocyte adipogenesis is associated with visceral obesity, visceral adipocyte hypertrophy, and a dysmetabolic state. Adipocyte 3, 197205.
30. Virtue, S & Vidal-Puig, A (2008) It’s not how fat you are, it’s what you do with it that counts. PLoS Biol 6, e237.
31. Luche, E, Cousin, B, Garidou, L, et al. (2013) Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism. Mol Metab 2, 281291.
32. Zhao, M & Chen, X (2015) Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors. Am J Physiol Endocrinol Metab 309, E334E344.
33. Faust, IM, Johnson, PR, Stern, JS, et al. (1978) Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol 235, E279E286.
34. Spalding, KL, Arner, E, Westermark, PO, et al. (2008) Dynamics of fat cell turnover in humans. Nature 453, 783787.
35. Charriere, G, Cousin, B, Arnaud, E, et al. (2003) Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 278, 98509855.
36. Cousin, B, Munoz, O, Andre, M, et al. (1999) A role for preadipocytes as macrophage-like cells. FASEB J 13, 305312.
37. Goldrick, RB (1967) Morphological changes in the adipocyte during fat deposition and mobilization. Am J Physiol 212, 777782.
38. Meyer, LK, Ciaraldi, TP, Henry, RR, et al. (2013) Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity. Adipocyte 2, 217226.
39. Skurk, T, Alberti-Huber, C, Herder, C, et al. (2007) Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92, 10231033.
40. O’Rourke, RW & Lumeng, CN (2013) Obesity heats up adipose tissue lymphocytes. Gastroenterology 145, 282285.
41. Lee, BC & Lee, J (2014) Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 1842, 446462.
42. Martinez, FO, Sica, A, Mantovani, A, et al. (2008) Macrophage activation and polarization. Front Biosci 13, 453461.
43. Locati, M, Mantovani, A & Sica, A (2013) Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol 120, 163184.
44. Mantovani, A, Biswas, SK, Galdiero, MR, et al. (2013) Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229, 176185.
45. Harford, KA, Reynolds, CM, McGillicuddy, FC, et al. (2011) Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 70, 408417.
46. Fujisaka, S, Usui, I, Bukhari, A, et al. (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58, 25742582.
47. Cinti, S, Mitchell, G, Barbatelli, G, et al. (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46, 23472355.
48. Aki, T, Funakoshi, T & Uemura, K (2015) Regulated necrosis and its implications in toxicology. Toxicology 333, 118126.
49. Schenk, S, Saberi, M & Olefsky, JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118, 29923002.
50. Zhang, J, Wright, W, Bernlohr, DA, et al. (2007) Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance. Am J Physiol Endocrinol Metab 292, E1433E1440.
51. Troseid, M, Nestvold, TK, Rudi, K, et al. (2013) Plasma lipopolysaccharide is closely associated with glycemic control and abdominal obesity: evidence from bariatric surgery. Diabetes Care 36, 36273632.
52. Milinovich, GJ, Burrell, PC, Pollitt, CC, et al. (2008) Microbial ecology of the equine hindgut during oligofructose-induced laminitis. ISME J 2, 10891100.
53. Qin, J, Li, R, Raes, J, et al. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 5965.
54. Xu, J & Gordon, JI (2003) Honor thy symbionts. Proc Natl Acad Sci U S A 100, 1045210459.
55. Devkota, S, Wang, Y, Musch, MW, et al. (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL-10–/– mice. Nature 487, 104108.
56. Lam, V, Su, J, Koprowski, S, et al. (2012) Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J 26, 17271735.
57. Santos, NC, Silva, AC, Castanho, MA, et al. (2003) Evaluation of lipopolysaccharide aggregation by light scattering spectroscopy. Chembiochem 4, 96100.
58. Furet, JP, Kong, LC, Tap, J, et al. (2010) Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 59, 30493057.
59. Louis, S, Tappu, RM, Damms-Machado, A, et al. (2016) Characterization of the gut microbial community of obese patients following a weight-loss intervention using whole metagenome shotgun sequencing. PLOS ONE 11, e0149564.
60. Ley, RE, Turnbaugh, PJ, Klein, S, et al. (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444, 10221023.
61. Duncan, SH, Lobley, GE, Holtrop, G, et al. (2008) Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes (Lond) 32, 17201724.
62. Schwiertz, A, Taras, D, Schafer, K, et al. (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190195.
63. Plichta, DR, Juncker, AS, Bertalan, M, et al. (2016) Transcriptional interactions suggest niche segregation among microorganisms in the human gut. Nat Microbiol 1, 16152.
64. Hardin, G (1960) The competitive exclusion principle. Science 131, 12921297.
65. Medzhitov, R & Horng, T (2009) Transcriptional control of the inflammatory response. Nat Rev Immunol 9, 692703.
66. Taira, R, Yamaguchi, S, Shimizu, K, et al. (2015) Bacterial cell wall components regulate adipokine secretion from visceral adipocytes. J Clin Biochem Nutr 56, 149154.
67. Cani, PD, Amar, J, Iglesias, MA, et al. (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 17611772.
68. Cani, PD, Possemiers, S, Van de Wiele, T, et al. (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58, 10911103.
69. Li, J, Lin, S, Vanhoutte, PM, et al. (2016) Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe –/– mice. Circulation 133, 24342446.
70. Lefebvre, P, Cariou, B, Lien, F, et al. (2009) Role of bile acids and bile acid receptors in metabolic regulation. Physiol Rev 89, 147191.
71. Islam, KB, 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, 17731781.
72. Kurdi, P, Kawanishi, K, Mizutani, K, et al. (2006) Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J Bacteriol 188, 19791986.
73. Hylemon, PB, Zhou, H, Pandak, WM, et al. (2009) Bile acids as regulatory molecules. J Lipid Res 50, 15091520.
74. Laugerette, F, Vors, C, Geloen, A, et al. (2011) Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation. J Nutr Biochem 22, 5359.
75. Erridge, C, Attina, T, Spickett, CM, et al. (2007) A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr 86, 12861292.
76. Ghoshal, S, Witta, J, Zhong, J, et al. (2009) Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 50, 9097.
77. Amar, J, Burcelin, R, Ruidavets, JB, et al. (2008) Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr 87, 12191223.
78. Laugerette, F, Furet, JP, Debard, C, et al. (2012) Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice. Am J Physiol Endocrinol Metab 302, E374E386.
79. Kallio, KA, Buhlin, K, Jauhiainen, M, et al. (2008) Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients. Innate Immun 14, 247253.
80. Levels, JH, Abraham, PR, van den Ende, A, et al. (2001) Distribution and kinetics of lipoprotein-bound endotoxin. Infect Immun 69, 28212828.
81. Wurfel, MM, Kunitake, ST, Lichenstein, H, et al. (1994) Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS. J Exp Med 180, 10251035.
82. Kong, LC, Holmes, BA, Cotillard, A, et al. (2014) Dietary patterns differently associate with inflammation and gut microbiota in overweight and obese subjects. PLOS ONE 9, e109434.
83. Wurfel, MM & Wright, SD (1997) Lipopolysaccharide-binding protein and soluble CD14 transfer lipopolysaccharide to phospholipid bilayers: preferential interaction with particular classes of lipid. J Immunol 158, 39253934.
84. Laugerette, F, Alligier, M, Bastard, JP, et al. (2014) Overfeeding increases postprandial endotoxemia in men: inflammatory outcome may depend on LPS transporters LBP and sCD14. Mol Nutr Food Res 58, 15131518.
85. Hailman, E, Albers, JJ, Wolfbauer, G, et al. (1996) Neutralization and transfer of lipopolysaccharide by phospholipid transfer protein. J Biol Chem 271, 1217212178.
86. Levels, JH, Marquart, JA, Abraham, PR, et al. (2005) Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein. Infect Immun 73, 23212326.
87. Park, BS, Song, DH, Kim, HM, et al. (2009) The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex. Nature 458, 11911195.
88. Triantafilou, M, Triantafilou, K & Fernandez, N (2000) Rough and smooth forms of fluorescein-labelled bacterial endotoxin exhibit CD14/LBP dependent and independent binding that is influencedby endotoxin concentration. Eur J Biochem 267, 22182226.
89. Everard, A, Geurts, L, Caesar, R, et al. (2014) Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status. Nat Commun 5, 5648.
90. Cai, L, Wang, Z, Ji, A, et al. (2012) Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity. PLOS ONE 7, e36785.
91. Zanoni, I, Ostuni, R, Marek, LR, et al. (2011) CD14 controls the LPS-induced endocytosis of toll-like receptor 4. Cell 147, 868880.
92. Hansen, LA, Poulsen, OM & Wurtz, H (1999) Endotoxin potency in the A549 lung epithelial cell bioassay and the limulus amebocyte lysate assay. J Immunol Methods 226, 4958.
93. Marshall, JC (2005) Lipopolysaccharide: an endotoxin or an exogenous hormone? Clin Infect Dis 41, Suppl. 7, S470S480.
94. Vishnyakova, TG, Bocharov, AV, Baranova, IN, et al. (2003) Binding and internalization of lipopolysaccharide by Cla-1, a human orthologue of rodent scavenger receptor B1. J Biol Chem 278, 2277122780.
95. Connelly, MA, Klein, SM, Azhar, S, et al. (1999) Comparison of class B scavenger receptors, CD36 and scavenger receptor BI (SR-BI), shows that both receptors mediate high density lipoprotein-cholesteryl ester selective uptake but SR-BI exhibits a unique enhancement of cholesteryl ester uptake. J Biol Chem 274, 4147.
96. Brundert, M, Heeren, J, Merkel, M, et al. (2011) Scavenger receptor CD36 mediates uptake of high density lipoproteins in mice and by cultured cells. J Lipid Res 52, 745758.
97. Moreira, AP, Texeira, TF, Ferreira, AB, et al. (2012) Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr 108, 801809.
98. Gazzano-Santoro, H, Meszaros, K, Birr, C, et al. (1994) Competition between rBPI23, a recombinant fragment of bactericidal/permeability-increasing protein, and lipopolysaccharide (LPS)-binding protein for binding to LPS and Gram-negative bacteria. Infect Immun 62, 11851191.
99. Takeuchi, O & Akira, S (2010) Pattern recognition receptors and inflammation. Cell 140, 805820.
100. Eldridge, MJ & Shenoy, AR (2015) Antimicrobial inflammasomes: unified signalling against diverse bacterial pathogens. Curr Opin Microbiol 23C, 3241.
101. Lu, A, Magupalli, VG, Ruan, J, et al. (2014) Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 156, 11931206.
102. Bauernfeind, F & Hornung, V (2013) Of inflammasomes and pathogens – sensing of microbes by the inflammasome. EMBO Mol Med 5, 814826.
103. Hagar, JA, Powell, DA, Aachoui, Y, et al. (2013) Cytoplasmic LPS activates caspase-11, implications in TLR4-independent endotoxic shock. Science 341, 12501253.
104. Kayagaki, N, Wong, MT, Stowe, IB, et al. (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341, 12461249.
105. Shi, J, Zhao, Y, Wang, Y, et al. (2014) Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187192.
106. Smith, C, Wang, X & Yin, H (2015) Caspases come together over LPS. Trends Immunol 36, 5961.
107. Halberg, N, Khan, T, Trujillo, ME, et al. (2009) Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29, 44674483.
108. Laforest, S, Labrecque, J, Michaud, A, et al. (2015) Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction. Crit Rev Clin Lab Sci 52, 301313.
109. Henning, MF, Sanchez, S & Bakas, L (2009) Visualization and analysis of lipopolysaccharide distribution in binary phospholipid bilayers. Biochem Biophys Res Commun 383, 2226.
110. Murano, I, Rutkowski, JM, Wang, QA, et al. (2013) Time course of histomorphological changes in adipose tissue upon acute lipoatrophy. Nutr Metab Cardiovasc Dis 23, 723731.
111. Lackey, DE & Olefsky, JM (2016) Regulation of metabolism by the innate immune system. Nat Rev Endocrinol 12, 1528.
112. Ilievski, V, Cho, Y, Katwala, P, et al. (2015) TLR4 expression by liver resident cells mediates the development of glucose intolerance and insulin resistance in experimental periodontitis. PLOS ONE 10, e0136502.
113. Shepherd, ML, Ponder, MA, Burk, AO, et al. (2014) Fibre digestibility, abundance of faecal bacteria and plasma acetate concentrations in overweight adult mares. J Nutr Sci 3, e10.
114. Turnbaugh, PJ, Ley, RE, Mahowald, MA, et al. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 10271031.
115. Fernandes, J, Su, W, Rahat-Rozenbloom, S, et al. (2014) Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes 4, e121.
116. Li, M, Gu, D, Xu, N, et al. (2014) Gut carbohydrate metabolism instead of fat metabolism regulated by gut microbes mediates high-fat diet-induced obesity. Benef Microbes 5, 335344.
117. Rahat-Rozenbloom, S, Fernandes, J, Gloor, GB, et al. (2014) Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes (Lond) 38, 15251531.
118. Murphy, EF, Cotter, PD, Healy, S, et al. (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59, 16351642.
119. Murugesan, S, Ulloa-Martinez, M, Martinez-Rojano, H, et al. (2015) Study of the diversity and short-chain fatty acids production by the bacterial community in overweight and obese Mexican children. Eur J Clin Microbiol Infect Dis 34, 13371346.
120. Perry, RJ, Peng, L, Barry, NA, et al. (2016) Acetate mediates a microbiome–brain–β cell axis to promote metabolic syndrome. Nature 534, 213217.
121. Kreier, F & Buijs, RM (2007) Evidence for parasympathetic innervation of white adipose tissue, clearing up some vagaries. Am J Physiol Regul Integr Comp Physiol 293, R548R549.
122. Kreier, F, Fliers, E, Voshol, PJ, et al. (2002) Selective parasympathetic innervation of subcutaneous and intra-abdominal fat – functional implications. J Clin Invest 110, 12431250.
123. Bartness, TJ, Liu, Y, Shrestha, YB, et al. (2014) Neural innervation of white adipose tissue and the control of lipolysis. Front Neuroendocrinol 35, 473493.
124. Vandanmagsar, B, Youm, YH, Ravussin, A, et al. (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17, 179188.

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