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

Gloria G. Guerrero M

Article ID: 1654
Vol 6, Issue 2, 2022

VIEWS - 408 (Abstract) 134 (PDF)

Abstract


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)

Full Text:

PDF


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




DOI: https://doi.org/10.24294/ti.v6.i2.1654

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 Gloria G. Guerrero M.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

This site is licensed under a Creative Commons Attribution 4.0 International License.