Adipsin – summing up large-scale results: A review

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Abstract

Adipsin is one of the first discovered adipokines – hormones produced by adipose tissue. Adipsin performs the function of a regulator of carbohydrate and lipid metabolism and participates in the adaptation of metabolism to the real needs of the body, being a powerful stimulant of anabolic processes. A characteristic feature of adipsin is that it is also a complement factor D, which is necessary for the normal functioning of an alternative pathway of activation of the complement system. Due to this, adipsin is represented in the body as a link between the energy block of the endocrine system and the humoral block of the immune system. Adipsin is known as a regulator of the function of pancreatic beta cells, a stimulator of lipogenesis, a modulator of inflammation processes. Recently, there have been works indicating the effect of adipsin on the microbiota, as well as its role in non-alcoholic fatty liver disease. To date, there are a large number of publications describing the biochemical structure, functions of adipsin, mechanisms of regulation of its synthesis, as well as changes in the level of adipsin in various pathological conditions. Attempts are also described to pharmacologically influence adipsin in order to modulate its functions or use it as a biomarker for the diagnosis of diseases. However, there is currently no structured review that summarizes and systematizes all available information about this adipokine. This is exactly the task we set ourselves in this study. The paper contains the results of all available studies on adipsin. In some cases, they are contradictory in nature, which indicates the need for further research in detecting connections between the body's systems.

About the authors

Vladimir V. Salukhov

Kirov Military Medical Academy

Author for correspondence.
Email: vlasaluk@yandex.ru
ORCID iD: 0000-0003-1851-0941

D. Sci. (Med.), Kirov Military Medical Academy

Russian Federation, Saint Petersburg

Yaroslav R. Lopatin

Kirov Military Medical Academy

Email: vlasaluk@yandex.ru
ORCID iD: 0000-0002-7008-3054

Cadet, Kirov Military Medical Academy

Russian Federation, Saint Petersburg

Alexey A. Minakov

Kirov Military Medical Academy

Email: minakom@mai.ru
ORCID iD: 0000-0003-1525-3601

Adjunct, Kirov Military Medical Academy

Russian Federation, Saint Petersburg

References

  1. El Husseny MW, Mamdouh M, Shaban S, et al. Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity. J Diabetes Res. 2017;2017:8095926. doi: 10.1155/2017/8095926
  2. Cohen P, Spiegelman BM. Cell biology of fat storage. Mol Biol Cell. 2016;27(16):2523-7. doi: 10.1091/mbc.E15-10-0749
  3. Sivakumar K, Bari MF, Adaikalakoteswari A, et al. Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy: novel placental secretion via Hofbauer cells. J Clin Endocrinol Metab. 2013;98(10):4113-22. doi: 10.1210/jc.2012-4293
  4. Ezure T, Sugahara M, Amano S. Senescent dermal fibroblasts negatively influence fibroblast extracellular matrix-related gene expression partly via secretion of complement factor D. Biofactors. 2019;45(4):556-62. doi: 10.1002/biof.1512
  5. Su X, Yan H, Huang Y, et al. Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus. Sci Rep. 2015;5:18588. doi: 10.1038/srep18588
  6. Pascual M, Catana E, White T, et al. Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D. Eur J Immunol. 1993;23(6):1389-92. doi: 10.1002/eji.1830230632
  7. Cianflone K, Xia Z, Chen LY. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta. 2003;1609(2):127-43. doi: 10.1016/s0005-2736(02)00686-7
  8. Lines SW, Richardson VR, Thomas B, et al. Complement and Cardiovascular Disease – The Missing Link in Haemodialysis Patients. Nephron. 2016;132(1):5-14. doi: 10.1159/000442426
  9. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-97. doi: 10.1038/ni.1923
  10. Ling M, Murali M. Analysis of the Complement System in the Clinical Immunology Laboratory. Clin Lab Med. 2019;39(4):579-90. doi: 10.1016/j.cll.2019.07.006
  11. Xu Y, Ma M, Ippolito GC, et al. Complement activation in factor D-deficient mice. Proc Natl Acad Sci U S A. 2001;98(25):14577-82. doi: 10.1073/pnas.261428398
  12. Irmscher S, Döring N, Halder LD, et al. Kallikrein Cleaves C3 and Activates Complement. J Innate Immun. 2018;10(2):94-105. doi: 10.1159/000484257
  13. Song NJ, Kim S, Jang BH, et al. Small Molecule-Induced Complement Factor D (Adipsin) Promotes Lipid Accumulation and Adipocyte Differentiation. PLoS One. 2016;11(9):e0162228. doi: 10.1371/journal.pone.0162228
  14. Hayashi M, Machida T, Ishida Y, et al. Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway. J Immunol. 2019;203(6):1411-6. doi: 10.4049/jimmunol.1900605
  15. Wiles JA, Galvan MD, Podos SD, et al. Discovery and Development of the Oral Complement Factor D Inhibitor Danicopan (ACH-4471). Curr Med Chem. 2020;27(25):4165-80. doi: 10.2174/0929867326666191001130342
  16. Tafere GG, Wondafrash DZ, Zewdie KA, et al. Plasma Adipsin as a Biomarker and Its Implication in Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes. 2020;13:1855-61. doi: 10.2147/DMSO.S253967
  17. Ohtsuki T, Satoh K, Shimizu T, et al. Identification of Adipsin as a Novel Prognostic Biomarker in Patients With Coronary Artery Disease. J Am Heart Assoc. 2019;8(23):e013716. doi: 10.1161/JAHA.119.013716
  18. Leivo-Korpela S, Lehtimäki L, Nieminen R, et al. Adipokine adipsin is associated with the degree of lung fibrosis in asbestos-exposed workers. Respir Med. 2012;106(10):1435-40. doi: 10.1016/j.rmed.2012.07.003
  19. Aradottir SS, Kristoffersson AC, Roumenina LT, et al. Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis. Front Immunol. 2021;12:690821. doi: 10.3389/fimmu.2021.690821
  20. Miner JL, Byatt JC, Baile CA, Krivi GG. Adipsin expression and growth in rats as influenced by insulin and somatotropin. Physiol Behav. 1993;54(2):207-12. doi: 10.1016/0031-9384(93)90100-t
  21. Flier JS, Cook KS, Usher P, Spiegelman BM. Severely impaired adipsin expression in genetic and acquired obesity. Science. 1987;237(4813):405-8. doi: 10.1126/science.3299706
  22. Lowell BB, Flier JS. Differentiation dependent biphasic regulation of adipsin gene expression by insulin and insulin-like growth factor-1 in 3T3-F442A adipocytes. Endocrinology. 1990;127(6):2898-906. doi: 10.1210/endo-127-6-2898
  23. Millar CA, Meerloo T, Martin S, et al. Adipsin and the glucose transporter GLUT4 traffic to the cell surface via independent pathways in adipocytes. Traffic. 2000;1(2):141-51. doi: 10.1034/j.1600-0854.2000.010206.x
  24. Ryu KY, Jeon EJ, Leem J, et al. Regulation of Adipsin Expression by Endoplasmic Reticulum Stress in Adipocytes. Biomolecules. 2020;10(2):314. doi: 10.3390/biom10020314
  25. Spiegelman BM, Lowell B, Napolitano A, et al. Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice. J Biol Chem. 1989;264(3):1811-5.
  26. Lenz M, Schönbauer R, Stojkovic S, et al. Long-term physical activity modulates adipsin and ANGPTL4 serum levels, a potential link to exercise-induced metabolic changes. Panminerva Med. 2021;15(11): e0239526. doi: 10.23736/S0031-0808.21.04382-2
  27. Wang Y, Zheng X, Xie X, et al. Body fat distribution and circulating adipsin are related to metabolic risks in adult patients with newly diagnosed growth hormone deficiency and improve after treatment. Biomed Pharmacother. 2020;132:110875. doi: 10.1016/j.biopha.2020.110875
  28. Napolitano A, Lowell BB, Flier JS. Alterations in sympathetic nervous system activity do not regulate adipsin gene expression in mice. Int J Obes. 1991;15(3):227-35.
  29. Lo JC, Ljubicic S, Leibiger B, et al. Adipsin is an adipokine that improves β cell function in diabetes. Cell. 2014;158(1):41-53. doi: 10.1016/j.cell.2014.06.005
  30. Wang JS, Lee WJ, Lee IT, et al. Association Between Serum Adipsin Levels and Insulin Resistance in Subjects With Various Degrees of Glucose Intolerance. J Endocr Soc. 2018;3(2):403-10. doi: 10.1210/js.2018-00359
  31. Gómez-Banoy N, Guseh JS, Li G, et al. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nat Med. 2019;25(11):1739-47. doi: 10.1038/s41591-019-0610-4
  32. Vasilenko MA, Kirienkova EV, Skuratovskaia DA, et al. The role of production of adipsin and leptin in the development of insulin resistance in patients with abdominal obesity. Dokl Biochem Biophys. 2017;475(1):271-6. doi: 10.1134/S160767291704010X
  33. Gursoy Calan O, Calan M, Yesil Senses P, et al. Increased adipsin is associated with carotid intima media thickness and metabolic disturbances in polycystic ovary syndrome. Clin Endocrinol (Oxf). 2016;85(6):910-7. doi: 10.1111/cen.13157
  34. Cianflone K, Maslowska M, Sniderman AD. Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Semin Cell Dev Biol. 1999;10(1):31-41. doi: 10.1006/scdb.1998.0272
  35. Cianflone K, Roncari DA, Maslowska M, et al. Adipsin/acylation stimulating protein system in human adipocytes: regulation of triacylglycerol synthesis. Biochemistry. 1994;33(32):9489-95. doi: 10.1021/bi00198a014
  36. Baldo A, Sniderman AD, St-Luce S, et al. The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis. J Clin Invest. 1993;92(3):1543-7. doi: 10.1172/JCI116733
  37. Rato Q, Cianflone K, Sniderman A. Sistema da adipsina – proteína estimuladora da acilação (ASP) e hiperapoB. Rev Port Cardiol. 1996;15(5):433-66.
  38. Goto H, Shimono Y, Funakoshi Y, et al. Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin. Oncogene. 2019;38(6):767-79. doi: 10.1038/s41388-018-0477-8
  39. Martínez-García MÁ, Moncayo S, Insenser M, et al. Metabolic Cytokines at Fasting and During Macronutrient Challenges: Influence of Obesity, Female Androgen Excess and Sex. Nutrients. 2019;11(11):2566. doi: 10.3390/nu11112566
  40. Schadt EE, Lamb J, Yang X, et al. An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet. 2005;37(7):710-7. doi: 10.1038/ng1589
  41. Liu L, Chan M, Yu L, et al. Adipsin deficiency does not impact atherosclerosis development in Ldlr-/-mice. Am J Physiol Endocrinol Metab. 2021;320(1):E87-92. doi: 10.1152/ajpendo.00440.2020
  42. Jones JR, Barrick C, Kim KA, et al. Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci U S A. 2005;102(17):6207-12. doi: 10.1073/pnas.0306743102
  43. Saleh J, Al-Maqbali M, Abdel-Hadi D. Role of Complement and Complement-Related Adipokines in Regulation of Energy Metabolism and Fat Storage. Compr Physiol. 2019;9(4):1411-29. doi: 10.1002/cphy.c170037
  44. Wang ZV, Scherer PE. Adiponectin, the past two decades. J Mol Cell Biol. 2016;8(2):93-100. doi: 10.1093/jmcb/mjw011
  45. Dahlke K, Wrann CD, Sommerfeld O, et al. Distinct different contributions of the alternative and classical complement activation pathway for the innate host response during sepsis. J Immunol. 2011;186(5):3066-75. doi: 10.4049/jimmunol.1002741
  46. Yu J, Yuan X, Chen H, et al. Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition. Blood. 2020;136(18):2080-9. doi: 10.1182/blood.2020008248
  47. Zhou T, Huang X, Zhou Y, et al. Associations between Th17-related inflammatory cytokines and asthma in adults: A Case-Control Study. Sci Rep. 2017;7(1):15502. doi: 10.1038/s41598-017-15570-8
  48. Korman BD, Marangoni RG, Hinchcliff M, et al. Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis. Arthritis Rheumatol. 2017;69(10):2062-8. doi: 10.1002/art.40193
  49. Leelahagul P, Bovornkitti S. Plasma adipokine levels in Thais. Asian Pac J Allergy Immunol. 2015;33(1):59-64. doi: 10.12932/AP0501.33.1.2015
  50. Qi H, Wei J, Gao Y, et al. Reg4 and complement factor D prevent the overgrowth of E. coli in the mouse gut. Commun Biol. 2020;3(1):483. doi: 10.1038/s42003-020-01219-2
  51. Dekker Nitert M, Mousa A, Barrett HL, et al. Altered Gut Microbiota Composition Is Associated With Back Pain in Overweight and Obese Individuals. Front Endocrinol (Lausanne). 2020;11:605. doi: 10.3389/fendo.2020.00605
  52. Tsuru H, Osaka M, Hiraoka Y, Yoshida M. HFD-induced hepatic lipid accumulation and inflammation are decreased in Factor D deficient mouse. Sci Rep. 2020;10(1):17593. doi: 10.1038/s41598-020-74617-5
  53. Qiu Y, Wang SF, Yu C, et al. Association of Circulating Adipsin, Visfatin, and Adiponectin with Nonalcoholic Fatty Liver Disease in Adults: A Case-Control Study. Ann Nutr Metab. 2019;74(1):44-52. doi: 10.1159/000495215
  54. Zhang J, Li K, Pan L, et al. Association of circulating adipsin with nonalcoholic fatty liver disease in obese adults: a cross-sectional study. BMC Gastroenterol. 2021;21(1):131. doi: 10.1186/s12876-021-01721-9
  55. Yilmaz Y, Yonal O, Kurt R, et al. Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease. Scand J Gastroenterol. 2011;46(1):91-7. doi: 10.3109/00365521.2010.516452
  56. Wuertz BR, Darrah L, Wudel J, Ondrey FG. Thiazolidinediones abrogate cervical cancer growth. Exp Cell Res. 2017;353(2):63-71. doi: 10.1016/j.yexcr.2017.02.020
  57. Tian Y, Kijlstra A, Webers CAB, Berendschot TTJM. Lutein and Factor D: two intriguing players in the field of age-related macular degeneration. Arch Biochem Biophys. 2015;572:49-53. doi: 10.1016/j.abb.2015.01.019
  58. Kassa E, Ciulla TA, Hussain RM, Dugel PU. Complement inhibition as a therapeutic strategy in retinal disorders. Expert Opin Biol Ther. 2019;19(4):335-42. doi: 10.1080/14712598.2019.1575358
  59. Heier JS, Pieramici D, Chakravarthy U, et al. Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials. Ophthalmol Retina. 2020;4(7):673-88. doi: 10.1016/j.oret.2020.01.019
  60. Loyet KM, Hass PE, Sandoval WN, et al. In Vivo Stability Profiles of Anti-factor D Molecules Support Long-Acting Delivery Approaches. Mol Pharm. 2019;16(1):86-95. doi: 10.1021/acs.molpharmaceut.8b00871
  61. Martel-Pelletier J, Raynauld JP, Dorais M, et al. The levels of the adipokines adipsin and leptin are associated with knee osteoarthritis progression as assessed by MRI and incidence of total knee replacement in symptomatic osteoarthritis patients: a post hoc analysis. Rheumatology (Oxford). 2016;55(4):680-8. doi: 10.1093/rheumatology/kev408
  62. Li Y, Zou W, Brestoff JR, et al. Fat-Produced Adipsin Regulates Inflammatory Arthritis. Cell Rep. 2019;27(10):2809-16.e3. doi: 10.1016/j.celrep.2019.05.032
  63. Gonzalez-Garza MT, Martinez HR, Cruz-Vega DE, et al. Adipsin, MIP-1b, and IL-8 as CSF Biomarker Panels for ALS Diagnosis. Dis Markers. 2018;2018:3023826. doi: 10.1155/2018/3023826
  64. Hietaharju A, Kuusisto H, Nieminen R, et al. Elevated cerebrospinal fluid adiponectin and adipsin levels in patients with multiple sclerosis: a Finnish co-twin study. Eur J Neurol. 2010;17(2):332-4. doi: 10.1111/j.1468-1331.2009.02701.x
  65. Vaňková M, Vacínová G, Včelák J, et al. Plasma levels of adipokines in patients with Alzheimer's disease – where is the "breaking point" in Alzheimer's disease pathogenesis?. Physiol Res. 2020;69(Suppl. 2):S339-49. doi: 10.33549/physiolres.934536
  66. Yang L, Qiu Y, Ling W, et al. Anthocyanins regulate serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes: a randomized controlled trial. Eur J Nutr. 2021;60(4):1935-44. doi: 10.1007/s00394-020-02379-x
  67. Lowell BB, Napolitano A, Usher P, et al. Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Endocrinology. 1990;126(3):1514-20. doi: 10.1210/endo-126-3-1514
  68. Diepvens K, Westerterp KR, Westerterp-Plantenga MS. Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R77-85. doi: 10.1152/ajpregu.00832.2005
  69. Antras J, Lasnier F, Pairault J. Adipsin gene expression in 3T3-F442A adipocytes is posttranscriptionally down-regulated by retinoic acid. J Biol Chem. 1991;266(2):1157-61.
  70. Lee M, Wathier M, Love JA, et al. Inhibition of aberrant complement activation by a dimer of acetylsalicylic acid. Neurobiol Aging. 2015;36(10):2748-56. doi: 10.1016/j.neurobiolaging.2015.06.018

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2. Fig. 1. Role of factor D (adipsin) in an alternative pathway of complement system activation.

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3. Fig. 2. Scheme of mutual influence of adipsin, insulin and adipose tissue.

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