Skip to main content

Advertisement

SpringerLink
Log in

Effects of a High-Fat Diet on Adipose Tissue CD8+ T Cells in Young vs. Adult Mice

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

T cells are involved in chronic inflammation of adipose tissue in obese conditions. However, the impact of age on the adipose T cells remains unknown. In this study, we investigated T cells in the white adipose tissue of young and adult mice. Obesity was induced in the mice using a high-fat diet (HFD) for 14 weeks. The young mice were fed an HFD at 3 weeks old, and adult mice were fed the HFD at 12 weeks old. Relative to adult mice, the young mice gained less fat and exhibited better glucose tolerance. Their adipose tissue contained more CD8+ T cells and higher levels of pro-inflammatory cytokines. Young mice showed a larger increase in CD4+ T cells. The young and adult mice showed similar insulin tolerance. HFD reduced the colon muscle layer, which was more obvious in the young mice. These data suggested that young and adult mice exhibit different responses to an HFD in terms of adipose tissue, glucose tolerance, and the colon muscle layer. The increase in CD8+ T cells and CD4+ T cells, together with higher levels of pro-inflammatory cytokines, suggested elevated inflammation in the presence of less fat gain in the young mice, which was unexpected. The significance of this inflammation remains unknown. We propose that inflammation might inhibit energy storage in the adipose tissue to provide more energy to the lean body mass in favor of growth in the young mice. The present study provides another example of the beneficial effect of inflammation in physiological conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Kopelman, P.G. 2000. Obesity as a medical problem. Nature 404 (6778): 635–643.

    CAS  PubMed  Google Scholar 

  2. Waki, H., and P. Tontonoz. 2007. Endocrine functions of adipose tissue. Annual Review of Pathology 2: 31–56.

    Article  CAS  PubMed  Google Scholar 

  3. Wu, D., Z. Ren, M. Pae, W. Guo, X. Cui, A.H. Merrill, and S.N. Meydani. 2007. Aging up regulates expression of inflammatory. Journal of Immunology 179 (7): 4829–4839.

    Article  CAS  Google Scholar 

  4. Lumeng, C.N., J. Liu, L. Geletka, C. Delaney, J. Delproposto, A. Desai, K. Oatmen, G. Martinez-Santibanez, A. Julius, S. Garg, and R.L. Yung. 2011. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. Journal of Immunology 187 (12): 6208–6216.

    Article  CAS  Google Scholar 

  5. Habbout, A., C. Guenancia, J. Lorin, E. Rigal, C. Fassot, L. Rochette, and C. Vergely. 2013. Postnatal overfeeding causes early shifts in gene expression in the heart and long-term alterations in cardiometabolic and oxidative parameters. PloS One 8 (2): e56981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Liu, Z., C.Y. Lim, M.Y. Su, S.L. Soh, G. Shui, M.R. Wenk, K.L. Grove, G.K. Radda, W. Han, and X. Xiao. 2013. Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic perturbations. The Journal of Endocrinology 219 (2): 131–143.

    Article  CAS  PubMed  Google Scholar 

  7. Rooney, B.L., M.A. Mathiason, and C.W. Schauberger. 2011. Predictors of obesity in childhood, adolescence, and adulthood in a birth cohort. Maternal and Child Health Journal 15 (8): 1166–1175.

    Article  PubMed  Google Scholar 

  8. Wensveen, F.M., V. Jelenčić, S. Valentić, M. Šestan, T.T. Wensveen, S. Theurich, A. Glasner, D. Mendrila, D. Štimac, F.T. Wunderlich, J.C. Brüning, O. Mandelboim, and B. Polić. 2015. NK cells link obesity-induced adipose stress to inflammation and insulin resistance. Nature Immunology 16 (4): 376–385.

    Article  CAS  PubMed  Google Scholar 

  9. Talukdar, S., D.Y. Oh, G. Bandyopadhyay, D. Li, J. Xu, J. McNelis, M. Lu, P. Li, Q. Yan, Y. Zhu, J. Ofrecio, M. Lin, M.B. Brenner, and J.M. Olefsky. 2012. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature Medicine 18 (9): 1407–1412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Elgazar-Carmon, V., A. Rudich, N. Hadad, and R. Levy. 2008. Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. Journal of Lipid Research 49 (9): 1894–1903.

    Article  CAS  PubMed  Google Scholar 

  11. Strissel, K.J., J. DeFuria, M.E. Shaul, G. Bennett, A.S. Greenberg, and M.S. Obin. 2010. T-cell recruitment and Th1 polarization in adipose tissue during diet-induced obesity in C57BL/6 mice. Obesity 18 (10): 1918–1925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Winer, S., G. Paltser, Y. Chan, H. Tsui, E. Engleman, D. Winer, and H.M. Dosch. 2009. Obesity predisposes to Th17 bias. European Journal of Immunology 39 (9): 2629–2635.

    Article  CAS  PubMed  Google Scholar 

  13. Mehta, P., A.M. Nuotio-Antar, and C.W. Smith. 2015. Gammadelta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice. Journal of Leukocyte Biology 97 (1): 121–134.

    Article  PubMed  Google Scholar 

  14. Liu, J., A. Divoux, J. Sun, J. Zhang, K. Clément, J.N. Glickman, G.K. Sukhova, P.J. Wolters, J. Du, C.Z. Gorgun, A. Doria, P. Libby, R.S. Blumberg, B.B. Kahn, G.S. Hotamisligil, and G.P. Shi. 2009. Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nature Medicine 15 (8): 940–945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nishimura, S., I. Manabe, M. Nagasaki, K. Eto, H. Yamashita, M. Ohsugi, M. Otsu, K. Hara, K. Ueki, S. Sugiura, and K. Yoshimura. 2009. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nature Medicine 15 (8): 914–920.

    Article  CAS  PubMed  Google Scholar 

  16. Lumeng, C.N., J.L. Bodzin, and A.R. Saltiel. 2007. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. The Journal of Clinical Investigation 117 (1): 175–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Weisberg, S.P., D. McCann, M. Desai, M. Rosenbaum, R.L. Leibel, and A.W. Ferrante. 2003. Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112 (12): 1796–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lumeng, C.N., and A.R. Saltiel. 2011. Inflammatory links between obesity and metabolic disease. The Journal of Clinical Investigation 121 (6): 2111–2117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xu, H., G.T. Barnes, Q. Yang, G. Tan, D. Yang, C.J. Chou, J. Sole, A. Nichols, J.S. Ross, L.A. Tartaglia, and H. Chen. 2003. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation 112 (12): 1821–1830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Osborn, O., and J.M. Olefsky. 2012. The cellular and signaling networks linking the immune system and metabolism in disease. Nature Medicine 18 (3): 363–374.

    Article  CAS  PubMed  Google Scholar 

  21. Mathis, D. 2013. Immunological goings-on in visceral adipose tissue. Cell Metabolism 17 (6): 851–859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ferrante, A.W., Jr. 2013. Macrophages, fat, and the emergence of immunometabolism. The Journal of Clinical Investigation 123 (12): 4992–4993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lumeng, C.N., S.M. Deyoung, J.L. Bodzin, and A.R. Saltiel. 2007. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 56 (1): 16–23.

    Article  CAS  PubMed  Google Scholar 

  24. Strissel, K.J., Z. Stancheva, H. Miyoshi, J.W. Perfield 2nd, J. DeFuria, Z. Jick, A.S. Greenberg, and M.S. Obin. 2007. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56 (12): 2910–2918.

    Article  CAS  PubMed  Google Scholar 

  25. Kayser, B.D., M.I. Goran, and S.G. Bouret. 2015. Perinatal overnutrition exacerbates adipose tissue inflammation caused by high-fat feeding in C57BL/6J mice. PloS One 10 (3): e0121954.

    Article  PubMed  PubMed Central  Google Scholar 

  26. López, M., S. Tovar, M.J. Vázquez, R. Nogueiras, L.M. Seoane, M. García, R.M. Señarís, and C. Diéguez. 2007. Perinatal overfeeding in rats results in increased levels of plasma leptin but unchanged cerebrospinal leptin in adulthood. International Journal of Obesity 31 (2): 371–377.

    Article  PubMed  Google Scholar 

  27. Lépinay, A.L., T. Larrieu, C. Joffre, N. Acar, I. Gárate, N. Castanon, G. Ferreira, B. Langelier, P. Guesnet, L. Brétillon, P. Parnet, S. Layé, and M. Darnaudéry. 2015. Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding. Psychoneuroendocrinology 53: 82–93.

    Article  PubMed  Google Scholar 

  28. Sasaki, A., W.C. de Vega, S. St-Cyr, P. Pan, and P.O. McGowan. 2013. Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood. Neuroscience 240: 1–12.

    Article  CAS  PubMed  Google Scholar 

  29. Guay, C., S.R. Madiraju, A. Aumais, E. Joly, and M. Prentki. 2007. A role for ATP citrate lyase, malic enzyme, and pyruvate/citrate cycling in glucose-induced insulin secretion. The Journal of Biological Chemistry 282 (49): 35657–35665.

    Article  CAS  PubMed  Google Scholar 

  30. Epstein, F.H., E.H. Choy, and G.S. Panayi. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. The New England Journal of Medicine 344: 907–916.

    Article  Google Scholar 

  31. Evans, J.L., I.D. Goldfine, B.A. Maddux, and Grodsky. 2002. Oxidative stress and stressactivated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrine Reviews 23: 599–622.

    Article  CAS  PubMed  Google Scholar 

  32. Suganami, T., J. Nishida, and Y. Ogawa. 2005. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes role of free fatty acids and tumor necrosis factor alpha. Arteriosclerosis, Thrombosis, and Vascular Biology 25: 2062–2068.

    Article  CAS  PubMed  Google Scholar 

  33. Suganami, T., K. Tanimoto-Koyama, J. Nishida, M. Itoh, X. Yuan, S. Mizuarai, H. Kotani, S. Yamaoka, K. Miyake, and S. Aoe. 2007. Role of the toll-like receptor 4/NF-κB pathway in saturated fatty acid induced inflammatory changes in the interaction between adipocytes and macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology 27: 84–91.

    Article  CAS  PubMed  Google Scholar 

  34. Hotamisligil, Gokhan S., Narinder S. Shargill, and B.M. Spiegelman. 1993. Adipose expression of tumor necrosis factor alpha: direct role in obesity-linked insulin resistance. Science 259 (2091): 87–91.

    Article  CAS  PubMed  Google Scholar 

  35. Teoman Uysal, K., Sarah M. Wiesbrock, M.W. Marino, and GkS Hotamisligil. 1997. Protection from obesity induced insulin resistance in mice lacking TNF-a function. Nature 389 (6651): 610–614.

  36. Yu, Lili, Guoyan Liu, Can Yang, Xiangfeng Song, and Hui Wang. 2016. Polyinosinic-polycytidylic acid inhibits the differentiation of mouse preadipocytes through pattern recognition receptor-mediated secretion of tumor necrosis factor-α. Immunology and Cell Biology 94 (9): 875–885.

    Article  CAS  PubMed  Google Scholar 

  37. Wisse, Brent E. 2004. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. Journal of the American Society of Nephrology 15: 2792–2800.

    Article  CAS  PubMed  Google Scholar 

  38. Wang, H., and J. Ye. 2015. Regulation of energy balance by inflammation: common theme in physiology and pathology. Reviews in Endocrine & Metabolic Disorders 16 (1): 47–54.

    Article  CAS  Google Scholar 

  39. Li, P., M. Lu, M.T. Nguyen, E.J. Bae, J. Chapman, D. Feng, M. Hawkins, J.E. Pessin, D.D. Sears, A.K. Nguyen, A. Amidi, S.M. Watkins, U. Nguyen, and J.M. Olefsky. 2010. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice. The Journal of Biological Chemistry 285: 15333–15345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li, P., M. Lu, M.T. Nguyen, E.J. Bae, J. Chapman, D. Feng, M. Hawkins, J.E. Pessin, D.D. Sears, A.K. Nguyen, A. Amidi, S.M. Watkins, U. Nguyen, and J.M. Olefsky. 2014. Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metabolism 20: 614–625.

    Article  Google Scholar 

  41. Xu, X., A. Grijalva, A. Skowronski, M. van Eijk, M.J. Serlie, and A.W. Ferrante Jr. 2013. Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation. Cell Metabolism 18: 816–830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zamarron, Brian F., Taleen A. Mergian, Kae Won Cho, Gabriel Martinez-Santibanez, Danny Luan, Kanakadurga Singer, Jennifer L. Del Proposto, Lynn M. Geletka, Lindsey A. Muir, and Carey N. Lumeng. 2017. Macrophage proliferation sustains adipose tissue inflammation in formerly obese mice. Diabetes 66 (2): 392–406.

    CAS  PubMed  Google Scholar 

  43. Qiao, L., B. Kinney, J. Schaack, and J. Shao. 2011. Adiponectin inhibits lipolysis in mouse adipocytes. Diabetes 60 (5): 1519–1527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kim, J.Y., E. van de Wall, M. Laplante, A. Azzara, M.E. Trujillo, S.M. Hofmann, T. Schraw, J.L. Durand, H. Li, G. Li, L.A. Jelicks, M.F. Mehler, D.Y. Hui, Y. Deshaies, G.I. Shulman, G.J. Schwartz, and P.E. Scherer. 2007. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. The Journal of Clinical Investigation 117 (9): 2621–2637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Park, P.H., H. Huang, M.R. McMullen, K. Bryan, and L.E. Nagy. 2008. Activation of cyclic-AMP response element binding protein contributes to adiponectin stimulated interleukin-10 expression in RAW 264.7 macrophages. Journal of Leukocyte Biology 83 (5): 1258–1266.

    Article  CAS  PubMed  Google Scholar 

  46. Folco, E.J., V.Z. Rocha, M. López-Ilasaca, and P. Libby. 2009. Adiponectin inhibits proinflammatory signaling in human macrophages independent of interleukin-10. The Journal of Biological Chemistry 284 (38): 25569–25575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jager, S., E.F. Stange, and J. Wehkamp. 2013. Inflammatory bowel disease: an impaired barrier disease. Langenbeck's Archives of Surgery / Deutsche Gesellschaft fur Chirurgie 398 (1): 1–12.

    Article  Google Scholar 

  48. Vaarala, O. 2012. Is the origin of type 1 diabetes in the gut? Immunology and Cell Biology 90 (3): 271–276.

    Article  CAS  PubMed  Google Scholar 

  49. Chia, L., and H. Yu. 2009. The epithelial gatekeeper against food allergy. Pediatrics and Neonatology 50 (6): 247–254.

    Article  Google Scholar 

  50. Agostini, L., F. Martinon, K. Burns, M.F. McDermott, P.N. Hawkins, and J T. 2004. NALP3 forms an IL-1β-processing inflammasome with increased activity in muckle-wells autoinflammatory disorder. Immunity 20 (3): 319–325.

    Article  CAS  PubMed  Google Scholar 

  51. Ohman, L., and M. Simren. 2010. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nature Reviews Gastroenterology & Hepatology 7 (3): 163–173.

    Article  Google Scholar 

  52. Bosi, E., L. Molteni, M.G. Radaelli, L. Folini, I. Fermo, E. Bazzigaluppi, L. Piemonti, M.R. Pastore, and R. Paroni. 2006. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia 49 (12): 2824–2827.

    Article  CAS  PubMed  Google Scholar 

  53. Ding, S., M.M. Chi, B.P. Scull, R. Rigby, N.M. Schwerbrock, S. Magness, C. Jobin, and P.K. Lund. 2010. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PloS One 5 (8): e12191.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kim, K.A., W. Gu, I.A. Lee, E.H. Joh, and D.H. Kim. 2012. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PloS One 7 (10): e47713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cani, P.D., R. Bibiloni, C. Knauf, A. Waget, A.M. Neyrinck, N.M. Delzenne, and R. Burcelin. 2008. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57 (6): 1470–1481.

    Article  CAS  PubMed  Google Scholar 

  56. Liou, A.P., M. Paziuk, J.M. Luevano Jr., S. Machineni, P.J. Turnbaugh, and L.M. Kaplan. 2013. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Science Translational Medicine 5 (178): 178ra41.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Tremaroli, V., and F. Backhed. 2012. Functional interactions between the gut microbiota and host metabolism. Nature 489 (7415): 242–249.

    Article  CAS  PubMed  Google Scholar 

  58. Koren, O., J.K. Goodrich, T.C. Cullender, A. Spor, K. Laitinen, H.K. Bäckhed, A. Gonzalez, J.J. Werner, and L.T. Angenent. 2012. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150 (3): 470–480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bäckhed, F., H. Ding, T. Wang, L.V. Hooper, G.Y. Koh, A. Nagy, C.F. Semenkovich, and J.I. Gordon. 2004. The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America 101 (44): 15718–15723.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hwang, I., Y.J. Park, Y.R. Kim, Y.N. Kim, S. Ka, H.Y. Lee, J.K. Seong, Y.J. Seok, and J.B. Kim. 2015. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity. FASEB Journal 29 (6): 2397–2411.

    Article  CAS  PubMed  Google Scholar 

  61. Suárez-Zamorano, N., S. Fabbiano, C. Chevalier, O. Stojanović, D.J. Colin, A. Stevanović, C. Veyrat-Durebex, V. Tarallo, D. Rigo, S. Germain, M. Ilievska, X. Montet, Y. Seimbille, S. Hapfelmeier, and M. Trajkovski. 2015. Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nature Medicine 21 (12): 1497–1501.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant numbers 81370915 and 81471559) and the Program for Innovative Research Team (in Science and Technology) at University of Henan Province (grant number 15IRTSTHN025). The authors are grateful to Dr. Yinming Liang for analysis of flow cytometry. We thank Ms. Wen Zhang and Mr. Zhitao Gao for their technical support. We also thank Professor Xianzhang Hu for his critical reading of the manuscript and suggestions.

Author information

Authors and Affiliations

  1. Research Center for Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, 453003, China

    Lijun Dong, Guoyan Liu & Hui Wang

  2. Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, Xinxiang Medical University, Xinxiang, Henan Province, 453003, China

    Yao Zhang & Hui Wang

  3. Department of Laboratory Medicine, Qindao Women and Children’s Hospital, Qindao, Shandong Province, 266034, China

    Li Yang

  4. Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, 70808, USA

    Jianping Ye

Authors
  1. Lijun Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guoyan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianping Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hui Wang.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest..

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dong, L., Zhang, Y., Yang, L. et al. Effects of a High-Fat Diet on Adipose Tissue CD8+ T Cells in Young vs. Adult Mice. Inflammation 40, 1944–1958 (2017). https://doi.org/10.1007/s10753-017-0635-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-017-0635-0

KEY WORDS

Search

Navigation