Trends in Immunotherapy

Review

Harnessing the crosstalk of adipocytes, autophagy, and immune cells for immunotherapy in obesity

Downloads

https://doi.org/10.24294/ti.v6.i2.1654
G. Guerrero M, G. (2022). Harnessing the crosstalk of adipocytes, autophagy, and immune cells for immunotherapy in obesity. Trends in Immunotherapy, 6(2). https://doi.org/10.24294/ti.v6.i2.1654
Volume 6 Issue 2 (2022)

Copyright

The authors shall retain the copyright of their work but allow the Publisher to publish, copy, distribute, and convey the work.

License

Trends in Immunotherapy (TI)  publishes accepted manuscripts under Creative Commons Attribution 4.0 International (CC BY 4.0). Authors who submit their papers for publication by TI agree to have the CC BY 4.0 license applied to their work, and that anyone is allowed to reuse the article or part of it free of charge for any purpose, including commercial use. As long as the author and original source are properly cited, anyone may copy, redistribute, reuse, and transform the content.

Authors

  • Gloria G. Guerrero M
    University Autonome of Zacatecas, Av Preparatoy S/N Col. Agronomicas Zacatecas, Zac. 98066, Mexico

As a self-degradative and recycling program, autophagy plays an essential role in homeostasis and life. The connection between autophagy and the status of the adipose tissue (white or beige/brown) links to metabolic diseases such as obesity, type two diabetes mellitus (T2DM). Moreover, autophagy and the renin-angiotensin physiological system play a pivotal role in metabolic syndrome, a disease that can disrupt homeostasis in different organs, including adipose tissue. The crosstalk in adipose tissue maintains low inflammation, brown adipocytes, and autophagic machinery under control. The JAK-STAT signalization pathway and the paracrine action of hormones, adipokines, and cytokines play a role in maintaining the status of low inflammation, brown adipocytes, and autophagic machinery to harness the utmost for obesity immunotherapy.

Keywords:

Autophagy Adipocytes Immune System Leptin Obesity Type Two Diabetes Mellitus (T2DM)

References

  1. Caballero B. Human against obesity. Who will win? Advances in Nutrition 2019; 10(suppl_1): S4–S9. doi: 10.1093/advances/nmy055
  2. WHO. Obesity and overweight [Internet]. 2021. Available from: https://www.WHO.Int/es/news-room/fact-sheets/detail/obesity-and-overweight
  3. Gutin B. Child obesity can be reduced with vigorous activity rather than restriction of energy intake. Obesity 2008; 16(10): 2193–2196. doi: 10.1038/oby.2008.348
  4. Hill JO, Wyatt HR, Peters JC. Energy balance and obesity. Circulation 2012; 126(1): 126–132. doi: 10.1161/CIRCULATIONAHA.111.087213
  5. Howell S, Kones R. “Calories in, calories out” and macronutrient intake: The hope, hype, and science of calories. American Journal of Physiology-Endocrinology and Metabolism 2017; 313(5): E608–E612. doi: 10.1152/ajpendo.00156.2017
  6. Namboong S, Cho Ch-S, Semple I, Lee JH. Autophagy dysregulation and obesity-associated pathologies. Molecules and Cells 2018; 41(1): 3–10. doi: 10.14348/molcells.2018.2213
  7. Shao F, Chen Y, Xu H, et al. Metabolic obesity phenotypes and risk of lung cancer: A Prospective cohort study of 450,482 UK biobank participants. Nutrients 2022; 14(16): 3370. doi: 10.3390/nu14163370
  8. Shinjyo N, Kita K. Infection and immunometabolism in the central nervous system: A possible mechanistic link between metabolic imbalance and dementia. Frontiers in Cellular Neuroscience 2021; 15: 765217. doi: 10.3389/fncel.2021.765217
  9. Flores-Cordero JA, Pérez-Pérez A, Jiménez-Cortegana C, et al. Obesity as a risk factor for dementia and Alzheimer’s disease: The role of leptin. International Journal of Molecular Sciences 2022; 23(9): 5202. doi: 10.3390/ijms23095202
  10. Liu J, Zhen D, Hu C, et al. Reconfiguration of gut microbiota and reprogramming of liver metabolism with phycobiliproteins bioactive peptides to rehabilitate obese rats. Nutrients 2022; 14(17): 3635. doi: 10.3390/nu14173635
  11. Wen X, Zhang B, Wu B, et al. Signaling pathways in obesity: Mechanisms and therapeutic interventions. Signal Transduction and Targeted Therapy 2022; 7(1): 298. doi: 10.1038/s41392-022-01149-x
  12. Ghaben AI, Scherer PE. Adipogenesis and metabolic health. Nature Reviews Molecular Cell Biology 2019; 20: 242–258. doi: 10.1038/s41580-018-0093-z
  13. Haider N, Larose L. Harnessing adipogenesis to prevent obesity. Adipocyte 2019; 8(1): 98–104. doi: 10.1080/21623945.2019.1583037
  14. Scheele C, Wofrum Ch. Brown adipose crosstalk in tissue plasticity and human metabolism. Endocrine Reviews 2020; 41: 53–65. doi: 10.1210/endrev/bnz007
  15. Haczeyni F, Bell-Anderson KS, Farrell GC. Cause and mechanism of adipocyte enlargement and adipose expansion. Obesity Reviews 2018; 19(3): 406–420. doi: 10.1111/obr.12646
  16. Longo M, Zatterale F, Naderi J, et al. Adipose tissue dysfunction as determinant of obesity-associated metabolic complications. International Journal of Molecular Sciences 2019; 20(9): 2358. doi: 10.3390/ijms20092358
  17. Jia L, Chen Z, Pan T, et al. TRIM67 deficiency exacerbates hypothalamic inflammation and fat accumulation in obese mice. International Journal of Molecular Sciences 2022; 23(16): 9438. doi: 10.3390/ijms23169438
  18. Ouchi N, Parker JI, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nature Reviews Immunology 2011; 11(2): 85–97. doi: 10.1038/nri2921
  19. Singla P, Bardoloi A, Parkash AA. Metabolic effects of obesity: A review. World Journal of Diabetes 2010; 1(3): 76–88. doi: 10.4239/wjd.v1.i3.76
  20. Caspar-Bauguil S, Cousin B, Bour S, et al. Adipose tissue lymphocytes and roles. Journal of Physiology and Biochemistry 2009; 65: 423–436. doi: 10.1007/BF03185938
  21. Richard AJ, Stephens JM. The role of JAK-STAT signaling in adipose tissue function. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2014; 1842(3): 431–439. doi: 10.1016/j.bbadis.2013.05.030
  22. Matsuzawa Y. Adiponectin: A key player in obesity related disorders. Current Pharmaceutical Design 2010; 16(17): 1896–1901. doi: 10.2174/138161210791208893
  23. Yamawaki H, Kuramoto J, Kameshima S, et al. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endotelial cells. Biochemical and Biophysical Research Communications 2011; 408: 339–343. doi: 10.1016/j.bbrc.2011.04.039
  24. AL-Suhaimi AE, Shehzad A. Leptin, resistin, and visfatin: The missing link between endocrine metabolic disorders and immunity. European Journal of Medical Research 2013; 18(1): 12. doi: 10.1186/2047-783X-18-12
  25. Kern L, Mittenbühler MJ, Vesting AJ, et al. Obesity-induced TNFα and IL-6 signaling: The missing link between obesity and inflammation-driven liver and colorectal cancers. Cancers 2018; 11(1): 24. doi: 10.3390/cancers11010024
  26. Freff J, Schwarte K, Bröker L, et al. Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa. Scientific Reports 2021; 11(1): 1125. doi: 10.1038/s41598-020-80693-4
  27. Herz CT, Kiefer FW. Adipose tissue browning in mice and humans. Journal of Endocrinology 2019; 241(3): R97–R109. doi: 10.1530/JOE.18-0598
  28. Ingelfinger F, De Feo D, Becher B. GM-CSF: Master regulator of the T cell-phagocyte interface during inflammation. Seminars in Immunology 2021; 54: 101518. doi: 10.1016/j.smim.2021.101518
  29. Ro S-H, Jang Y, Bae J, et al. Autophagy in adipocyte browning: Emerging drug target for intervention in obesity. Frontiers in Physiology 2019; 10: 22. doi: 10.3389/fphys.2019.00022
  30. Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, aging, and disease. Nature Reviews Molecular Cell Biology 2020; 21(4): 183–203. doi: 10.1038/s41580-019-0199-y
  31. Morishita H, Mizushima N. Diverse cellular roles of autophagy. Annual Review of Cell and Developmental Biology 2019; 35: 3.1–3.23. doi: 10.1146/annual-cellbio-100818-125300
  32. Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity 2021; 54(3): 437–453. doi: 10.1016/j.immuni.2021.01.018
  33. Wang J, Liao B, Wang C, et al. Effects of antioxidant supplementation on metabolic disorders in obese patients from randomized clinical controls: A meta-analysis and systematic review. Oxidative Medicine and Cellular Longevity 2022; 2022: 7255413. doi: 10.1155/2022/7255413
  34. Zhang Y, Goldman S, Baerga R, et al. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis. Proceedings of the National Academy of Sciences 2009; 106(47): 19860–19865. doi: 10.1073/pnas.0906048106
  35. Quan W, Lee MS. Role of autophagy in the control of body metabolism. Endocrinology and Metabolism 2013; 28(1): 6–11. doi: 10.3803/EnM.2013.28.1.6
  36. Kovsan J, Bluher M, Tarnovscki T, et al. Altered autophagy in human adipose tissues in Obesity. The Journal of Clinical Endocrinology and Metabolism 2011; 96(2): E268–E277. doi: 10.1210/jc.2010-1681
  37. Boya P, Reggiori F, Codogno P. Emerging regulation and functions of autophagy. Nature Cell Biology 2013; 15(7): 713–720. doi: 10.1038/ncb2788
  38. Zheng ZG, Zhu ST, Cheng HM, et al. Discovery of a potent SCAP degrader that ameliorates HFD-induced obesity, hyperlipidemia and insulin resistance via an autophagy-independent lysosomal pathway. Autophagy 2021; 17(7): 1592–1613. doi: 10.1080/15548627.2020.1757955
  39. Menikdiwela KR, Ramalingam L, Rasha F, et al. Autophagy in metabolic syndrome: Breaking the wheel by targeting the renin-angiotensin system. Cell Death & Disease 2020; 11: 87–94. doi: 10.1038/s41419-020-2275
  40. Park HS, Song JW, Park JH, et al. TXNIP/VDUP1 attenuates steatohepatitis via autophagy and fatty acid oxidation. Autophagy 2021; 17(9): 2549–2564. doi: 10.1080/15548627.2020.1834711
  41. Yang H, Wen Y, Zhang M, et al. MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint. Autophagy 2020; 16(2): 271–288. doi: 10.1080/15548627.2019.1606647
  42. Karampela I, Christodoulatos GS, Dalamaga M. The role of adipose tissue and adipokines in sepsis: Inflammatory and metabolic considerations, and the obesity paradox. Current Obesity Reports 2019; 8(4): 434–457. doi: 10.1007/s13679-019-00360-2
  43. Mizushima N. Autophagy: Process and function. Genes & Development 2017; 21(22): 2861–2873.
  44. Cristancho AG, Lazar MA. Forming functional fat: A growing understanding of adipocyte differentiation. Nature Reviews Molecular Cell Biology 2011; 12: 722–734. doi: 10.1038/nrm3198
  45. Sarjeant K, Stephens JM. Adipogenesis. Cold Spring Harbor Perspectives in Biology 2012; 4: a008417–a008436.
  46. Chun Y, Kim K. Autophagy: An essential degradation program for cellular homeostasis and life. Cells 2018; 7(12): 278–304. doi: 10.3390/cells7120278
  47. Qian M, Fang X, Wang X. Autophagy and inflammation. Clinical and Translational Medicine 2017; 6(1): e24. doi: 10.1186/s40169-017-0154-5
  48. Yuan ML, Wang T. The new mechanism of Ghrelin/GHSR-1a on autophagy regulation. Peptides 2020; 126: 170264. doi: 10.1016/j.peptides.2020.170264
  49. Tao T, Xu H. Autophagy and obesity and diabetes. In: Le W (editor). Autophagy: Biology and diseases. Advances in experimental medicine and biology, vol 1207. Singapore: Springer; 2020. p. 445–461. doi: 10.1007/978-981-15-4272-5_32
  50. Delgado MA, Elmaoued RA, David AS, et al. Toll-like receptors control autophagy. The EMBO Journal 2008; 27(7): 1110–1121. doi: 10.1038/emboj.2008.31
  51. Levine RI, Hubbard SR. Unlocking the secrets to Janus kinase activation. Science 2022; 376(6589): 139–140. doi: 10.1126/Science.Abo7788
  52. Deretic V, Levine B. Autophagy balance inflammation in innate immunity. Autophagy 2018; 14: 243–251.
  53. Hu Y, Reggiori F. Molecular regulation of autophagosome formation. Biochemical Society Transactions 2022; 50(1): 55–69. doi: 10.1042/BST20210819.
  54. Mizushima N, Levine B. Autophagy in human diseases. New England Journal of Medicine 2020; 383(16): 1564–1576. doi: 10.1056/NEJMra2022774
  55. Zhao YG, Zhang H. Formation and maturation of autophagosomes in higher eukaryotes: A social network. Current Opinion in Cell Biology 2018; 53: 29–36. doi: 10.1016/j.ceb.2018.04.003
  56. Wang Z, Nakayama T. Inflammation, a link between obesity and cardiovascular disease. Mediators of Inflammation 2010; 2010: 535918. doi: 10.1155/2010/535918
  57. Singh R, Xiang Y, Wang Y, et al. Autophagy regulates adipose mass and differentiation in mice. The Journal of Clinical Investigation 2009; 119(11): 3329–3339. doi: 10.1172/JCI39228
  58. Farkhondeh T, Llorens S, Pourbagher-Shahri AM, et al. An overview of the role of adipokines in cardiometabolic diseases. Molecules 2020; 25(21): 5218. doi: 10.3390/molecules25215218
  59. Miller BC, Zhan Z, Stephenson LM, et al. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 2008; 4(3): 309–314. doi: 10.4161/auto.5474
  60. Clarke AJ, Simon AK. Autophagy in the renewal differentiation and homeostasis of immune cells. Nature Reviews Immunology 2019; 19(3): 170–183. doi: 10.1038/s41577-018-0095-2
  61. Mills EL, Kelly B, O’Neill LAJ. Mitochondria are the powerhouses of immunity. Nature Immunology 2017; 18; 488–498. doi: 10.1038/ni.3704
  62. Villarino A, Laurence A, Robinson GW, et al. Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions. eLife 2016; 5: e08384. doi: 10.7554/eLife.08384
  63. Gonciarz M, Pawlak-Bus, Leszczynski P, Owczarek W. TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases. Immunotherapy 2021; 13(13): 1135–1150. doi: 10.2217/imt-2021-0096
  64. Kumar S, Jain A, Choi SW, et al. Mammalian Atg8-family proteins are upstream regulators of the lysosomal system by controlling mTOR and TFEB. Autophagy 2020; 16: 2305–2306. doi: 10.1080/15548627.2020.1837423
  65. Khan IM, Dai Perrard XY, Perrard JL, et al. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. Atherosclerosis 2014; 233(2): 419–428. doi: 10.1016/j.atherosclerosis.2014.01.011