Introduction: Obesity is a complex multifactorial disorder that is characterized by excessive accumulation of white adipose tissue and can lead to the development of metabolic diseases such as type 2 diabetes mellitus, non-alcoholic fatty liver disease, cardiovascular disease, and various types of cancer.
Aim: The aim of the present study is to provide a systematic review of scientific publications in the field of obesity and the general mechanisms between inflammation and carcinogenesis. Results: For the period from 1999 to 2022, in the accessible databases Scopus, ScienceDirect, Web of Science, PubMed, UpToDate, by keywords: obesity, inflammation and cancer, were found in 58 508 publications, of which 24 406 were review articles, book chapters, and 25 948 publications, research results, abstracts, posters.
Adipose tissue is a complex dynamic endocrine system that secretes hormones, cytokines, and circulating microribonucleic acids (miRNAs), which regulate metabolic homeostasis, adipocyte differentiation and hypertrophy, infiltration and polarization of macrophages, metainflammation, insulin resistance and tumor microenvironment. miRNAs can act as both oncomirs and tumor suppressor factors.
Conclusion: miRNAs are appropriate markers that can detect adipocyte differentiation, adipogenesis, and hormonal homeostasis disorders associated with metabolic syndrome, obesity, or cancer. Ongoing in-depth analyses in this area are needed.
Alberti KGM, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet (2005) 366:1059–62. doi: 10.1016/S0140-6736 (05)67402-8
Alexander R, Lodish H, Sun L. MicroRNAs in adipogenesis and as therapeutic targets forobesity. Expert Opin Ther Targets (2011) 5:623–36. doi: 10.1517/14728222.2011.561317
Cinti S. Pink Adipocytes. Trends Endocrinol Metab (2018) 29:651–66. doi: 10.1016/j.tem.2018.05.007
Corrê a LH, Heyn GS, Magalhaes KG. The Impact of the Adipose Organ Plasticity on Inflammation and Cancer Progression. Cells (2019) 8:662. doi: 10.3390/cells8070662
De Pergola G, Silvestris F. Obesity as a major risk factor for cancer. J Obes (2013) 2013:291546
Deiuliis JA. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. Int J Obes (2016) 40:88–101. doi: 10.1038/ijo.2015.170
Deshmukh AS, Peijs L, Beaudry JL, Jespersen NZ, Nielsen CH, Ma T, et al. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine. Cell Metab (2019) 30:963–975.e7
Ejarque M, Ceperuelo-Mallafré V, Serena C, Maymo-Masip E, Duran X, Dı́az-Ramos A, et al. Adipose tissue mitochondrial dysfunction in human obesity is linked to a specific DNA methylation signature in adipose-derived stem cells. Int J Obes (2019) 43:1256–68. doi: 10.1038/s41366-018-0219-6
Faria SS, Corrê a LH, Heyn GS, de Sant’Ana LP, Almeida RDN, Magalhães KG. Obesity and breast cancer: The role of crown-like structures in breast adipose tissue in tumor progression, prognosis, and therapy. J Breast Cancer (2020) 23:233–45. doi: 10.4048/jbc.2020.23.e35
Feng YH. The association between obesity and gynecological cancer. Gynecol Minim Invasive Ther (2015) 4:102–5. doi: 10.1016/j.gmit.2015.03.003
Ginsberg HN, MacCallum PR. The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: Part I. Increased cardiovascular disease risk and the importance of atherogenic dyslipidemia in persons with the metabolic syndrome and type 2 diabetes mellitus. J Cardiometab Syndr (2009) 4:113–9
Giordano A, Smorlesi A, Frontini A, Barbatelli G, Cinti S. MECHANISMS IN ENDOCRINOLOGY: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ. Eur J Endocrinol (2014) 170: R159–71. doi: 10.1530/EJE-13-0945
Gordon S, Martinez FO. Alternative activation of macrophages: Mechanism and functions. Immunity (2010) 32:593–604. doi: 10.1016/j.immuni. 2010.05.007
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and Management of the Metabolic Syndrome. Circulation (2005) 112:2735–52. doi: 10.1161/CIRCULATIONAHA.105.169404
Gual P, Le Marchand-Brustel Y, Tanti JF. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie (2005) 87:99– 109. doi: 10.1016/j.biochi.2004.10.019
Han MS, Jung DY, Morel C, Lakhani SA, Kim JK, Flavell RA, et al. JNK Expression by Macrophages Promotes Obesity-induced Insulin Resistance and Inflammation. Sci (80- ) (2013) 339:218–22. doi: 10.1038/jid.2014.371
Hanahan D, Weinberg R. The Hallmarks of Cancer. Cell (2000) 100:57–70. doi: 10.1016/S0092-8674(00)81683-9
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell (2011) 144:646–74. doi: 10.1016/j.cell.2011.02.013
Heyn GS, Corre a LH and Magalhães KG. The Impact of Adipose Tissue–Derived miRNAs in Metabolic Syndrome, Obesity, and Cancer. Front. Endocrinol. (2020) 11:563816.doi: 10.3389/fendo.2020.56381
Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Rapid Publication Obesity and Insulin Resistance. J Clin Invest (1995) 95:2409–15. doi: 10.1172/JCI117936.Rapid
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature (2017) 542:177–85. doi: 10.1038/nature21363
Howe LR, Subbaramaiah K, Hudis CA, Dannenberg AJ. Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer. Clin Cancer Res (2013) 19:6074–83. doi: 10.1158/1078-0432.CCR- 12-2603
Huang C, Liu XJ, QunZhou, Xie J, Ma TT, Meng XM, et al. MiR-146a modulates macrophage polarization by inhibiting Notch1 pathway in RAW264.7 macrophages. Int Immunopharmacol (2016) 32:46–54. doi: 10.1016/j.intimp.2016.01.009
Ikeda K, Maretich P, Kajimura S. The Common and Distinct Features of Brown and Beige Adipocytes. Trends Endocrinol Metab (2018) 29:191–200
Jung UJ, Choi MS. Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci (2014) 15:6184–223. doi: 10.3390/ijms15046184
Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, et al. The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PloS One (2016) 11:1–14
Koliaki C, Liatis S, Kokkinos A. Obesity and cardiovascular disease: revisiting an old relationship. Metabolism (2019) 92:98–107. doi: 10.1016/j.metabol.2018.10.011
Kulyté A, Kwok KHM, de Hoon M, Carninci P, Hayashizaki Y, Arner P, et al. MicroRNA-27a/b-3p and PPARG regulate SCAMP3 through a feed- forward loop during adipogenesis. Sci Rep (2019) 9:13891. doi: 10.1038/s41598-019-50210-3
Landrier J-F, Derghal A, Mounien L. MicroRNAs in Obesity and Related Metabolic Disorders. Cells (2019) 8:859. doi: 10.3390/cells8080859
Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: A metaanalysis of cohort studies. Br J Cancer (2007) 97:1005–8. doi: 10.1038/ sj.bjc.6603932
Lavalette C, Cénée S, Rebillard X, Lamy P-J, Trétarre B, Menegaux F. Abdominal obesity and prostate cancer risk: epidemiological evidence from the EPICAP study. Rev Epidemiol Sante Publique (2018) 66:S248. doi: 10.1016/j.respe.2018.05.040
Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M, et al. Association of Obesity with Risk of Early-Onset Colorectal Cancer among Women. JAMA Oncol (2019) 5:37–44. doi: 10.1001/jamaoncol.2018.4280
Liu X, Sun Q, Hou H, Zhu K, Wang Q, Liu H, et al. The association between BMI and kidney cancer risk. Med (Balt) (2018) 97:e12860. doi: 10.1097/ md.0000000000012860
Liu Y-C, Zou X-B, Chai Y-F, Yao Y-M. Macrophage Polarization in Inflammatory Diseases. Int J Biol Sci (2014) 10:520–9. doi: 10.7150/ijbs.8879
Lumeng CN, Delproposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes (2008) 57:3239–46. doi: 10.2337/db08-0872
Ogawa R, Tanaka C, Sato M, Nagasaki H, Sugimura K, Okumura K, et al. Adipocyte-derived microvesicles contain RNA that is transported into macrophages and might be secreted into blood circulation. Biochem Biophys Res Commun (2010) 398:723–9. doi: 10.1016/j.bbrc.2010.07.008
Olefsky JM, Glass CK. Macrophages, Inflammation, and Insulin Resistance. Annu Rev Physiol (2010) 72:219–46. doi: 10.1146/annurev-physiol-021909-135846
Peirce V, Carobbio S, Vidal-Puig A. The different shades of fat. Nature (2014) 510:76–83. doi: 10.1038/nature13477
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther (2016) 1:15004. doi: 10.1038/sigtrans.2015.4
Raggi F, Pelassa S, Pierobon D, Penco F, Gattorno M, Novelli F, et al. Regulation of human Macrophage M1-M2 Polarization Balance by hypoxia and the Triggering receptor expressed on Myeloid cells-1. Front Immunol (2017) 8:1097. doi: 10.3389/fimmu.2017.01097
Sergentanis TN, Zagouri F, Tsilimidos G, Tsagianni A, Tseliou M, Dimopoulos MA, et al. Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses. Clin Lymphoma Myeloma Leuk (2015) 15:563– 577.e3. doi: 10.1016/j.clml.2015.06.003
Shao C, Bai LP, Qi ZY, Hui GZ, Wang Z. Overweight, obesity and meningioma risk: Ameta-analysis. PloS One (2014) 9:1–7. doi: 10.1371/ journal.pone.0090167
Sharma P. Inflammation and the Metabolic Syndrome. Indian J Biochem (2011) 26:317–8. doi: 10.1155/2010/289645.123
Svoronos AA, Engelman DM, Slack FJ. OncomiR or Tumor Suppressor? The Duplicity of MicroRNAs in Cancer. Cancer Res (2016) 76:3666–70. doi: 10.1158/0008-5472.CAN-16-0359
Turati F, Tramacere I, La Vecchia C, Negri E. A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Ann Oncol (2013) 24:609–17. doi: 10.1093/annonc/mds244
Villarroya J, Cereijo R, Gavaldà-Navarro A, Peyrou M, Giralt M, Villarroya F. New insights into the secretory functions of brown adipose tissue. J Endocrinol (2019) 243:R19–27. doi: 10.1530/JOE-19-0295
Weisberg SP, Mccann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation. J Clin Invest (2003) 12:112. doi: 10.1172/JCI200319246
Withers SB, Dewhurst T, Hammond C, Topham CH. MiRNAs as novel adipokines: Obesity-related circulating MiRNAsinfluence chemosensitivity in cancer patients. Non Cod RNA (2020) 6:1–29. doi: 10.3390/ncrna6010005
Xu X, Grijalva A, Skowronski A, van Eijk M, Serlie MJ, Ferrante AW. Obesity Activates a Program of Lysosomal-Dependent Lipid Metabolism in Adipose Tissue Macrophages Independently of Classic Activation. Cell Metab (2013) 18:816–30. doi: 10.1016/j.cmet.2013.11.001
Yang P, Zhou Y, Chen B, Wan HW, Jia GQ, Bai HL, et al. Overweight, obesity and gastric cancer risk: Results from a meta-analysis of cohort studies. Eur J Cancer (2009) 45:2867–73. doi: 10.1016/j.ejca.2009.04.019
Zhao ZG, Guo XG, Ba CX, Wang W, Yang YY, Wang J, et al. Overweight, obesity and thyroid cancer risk: A meta-analysis of cohort studies. J Int Med Res (2012) 40:2041–50. doi: 10.1177/03000605120400060
