Adipose-derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis.

Publisher: Blackwell Publishing Country of Publication: England NLM ID: 100897395 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1467-789X (Electronic) Linking ISSN: 14677881 NLM ISO Abbreviation: Obes Rev Subsets: MEDLINE

Publication: <2002->: Oxford, UK : Blackwell Publishing
Original Publication: Oxford, UK : Blackwell Science, c2000-

Obesity*/genetics ; Obesity*/complications ; MicroRNAs*/metabolism ; Computational Biology* ; Adipose Tissue*/metabolism ; Biomarkers*/blood ; Biomarkers*/metabolism; Humans

Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.
(© 2024 World Obesity Federation.)

Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body‐mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363(23):2211‐2219. doi:10.1056/NEJMoa1000367.
Whitlock G, Lewington S, Sherliker P, et al. Body‐mass index and cause‐specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083‐1096. doi:10.1016/S0140‐6736(09)60318‐4.
Obesity and overweight fact sheet, 2020. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. WHO; 2020.
Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large‐scale association analysis. Nat Genet. 2010;42(7):579‐589. doi:10.1038/ng.609.
Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288‐298. doi:10.1038/s41574‐019‐0176‐8.
Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79(1):351‐379. doi:10.1146/annurev‐biochem‐060308‐103103.
Mori MA, Ludwig RG, Garcia‐Martin R, Brandão BB, Kahn CR. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 2019;30(4):656‐673. doi:10.1016/j.cmet.2019.07.011.
Stern JH, Rutkowski JM, Scherer PE. Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metab. 2016;23(5):770‐784. doi:10.1016/j.cmet.2016.04.011.
Thomou T, Mori MA, Dreyfuss JM, et al. Adipose‐derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017;542(7642):450‐455. doi:10.1038/nature21365.
Brandao BB, Lino M, Kahn CR. Extracellular miRNAs as mediators of obesity‐associated disease. J Physiol. 2022;600(5):1155‐1169. doi:10.1113/JP280910.
Ji C, Guo X. The clinical potential of circulating microRNAs in obesity. Nat Rev Endocrinol. 2019;15(12):731‐743. doi:10.1038/s41574‐019‐0260‐0.
Oses M, Margareto Sanchez J, Portillo MP, Aguilera CM, Labayen I. Circulating miRNAs as biomarkers of obesity and obesity‐associated comorbidities in children and adolescents: a systematic review. Nutrients. 2019;11(12):11. doi:10.3390/nu11122890.
Alfano R, Robinson O, Handakas E, Nawrot TS, Vineis P, Plusquin M. Perspectives and challenges of epigenetic determinants of childhood obesity: a systematic review. Obes Rev. 2022;23(Suppl 1):e13389. doi:10.1111/obr.13389.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.
Lewandowski P, Goławski M, Baron M, Reichman‐Warmusz E, Wojnicz R. A systematic review of miRNA and cfDNA as potential biomarkers for liquid biopsy in myocarditis and inflammatory dilated cardiomyopathy. Biomolecules. 2022;12(10):12. doi:10.3390/biom12101476.
Nunez Lopez YO, Casu A, Kovacova Z, et al. Coordinated regulation of gene expression and microRNA changes in adipose tissue and circulating extracellular vesicles in response to pioglitazone treatment in humans with type 2 diabetes. Front Endocrinol. 2022;13:955593. doi:10.3389/fendo.2022.955593.
Tong Z, Cui Q, Wang J, Zhou Y. TransmiR v2.0: an updated transcription factor‐microRNA regulation database. Nucleic Acids Res. 2019;47(D1):D253‐d58. doi:10.1093/nar/gky1023.
Bu D, Luo H, Huo P, et al. KOBAS‐i: intelligent prioritization and exploratory visualization of biological functions for gene enrichment analysis. Nucleic Acids Res. 2021;49(W1):W317‐w25. doi:10.1093/nar/gkab447.
Lozano‐Bartolome J, Llaurado G, Portero‐Otin M, et al. Altered expression of miR‐181a‐5p and miR‐23a‐3p is associated with obesity and TNF alpha‐induced insulin resistance. J Clin Endocrinol Metab. 2018;103(4):1447‐1458. doi:10.1210/jc.2017‐01909.
Murri M, Insenser M, Fernández‐Durán E, San‐Millán JL, Escobar‐Morreale HF. Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on circulating miRNA‐21, miRNA‐27b, miRNA‐103, and miRNA‐155 expression. J Clin Endocrinol Metab. 2013;98(11):E1835‐E1844. doi:10.1210/jc.2013‐2218.
Cereijo R, Taxerås SD, Piquer‐Garcia I, et al. Elevated levels of circulating miR‐92a are associated with impaired glucose homeostasis in patients with obesity and correlate with metabolic status after bariatric surgery. Obes Surg. 2020;30(1):174‐179. doi:10.1007/s11695‐019‐04104‐y.
Pescador N, Pérez‐Barba M, Ibarra JM, Corbatón A, Martínez‐Larrad MT, Serrano‐Ríos M. Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS ONE. 2013;8(10):e77251. doi:10.1371/journal.pone.0077251.
Ortega FJ, Mercader JM, Catalán V, et al. Targeting the circulating microRNA signature of obesity. Clin Chem. 2013;59(5):781‐792. doi:10.1373/clinchem.2012.195776.
Bae Y‐U, Kim Y, Lee H, et al. Bariatric surgery alters microRNA content of circulating exosomes in patients with obesity. Obesity. 2019;27(2):264‐271. doi:10.1002/oby.22379.
Choi WH, Ahn J, Um MY, Jung CH, Jung SE, Ha TY. Circulating microRNA expression profiling in young obese Korean women. Nutr Res Pract. 2020;14(4):412‐422. doi:10.4162/nrp.2020.14.4.412.
Kim NH, Ahn J, Choi YM, et al. Differential circulating and visceral fat microRNA expression of non‐obese and obese subjects. Clin Nutr. 2020;39(3):910‐916. doi:10.1016/j.clnu.2019.03.033.
Kim H, Bae YU, Lee H, et al. Effect of diabetes on exosomal miRNA profile in patients with obesity. BMJ Open Diabetes Res Care. 2020;8(1):8. doi:10.1136/bmjdrc‐2020‐001403.
Pek SLT, Sum CF, Lin MX, et al. Circulating and visceral adipose miR‐100 is down‐regulated in patients with obesity and type 2 diabetes. Mol Cell Endocrinol. 2016;427:112‐123. doi:10.1016/j.mce.2016.03.010.
Wang YC, Li Y, Wang XY, et al. Circulating miR‐130b mediates metabolic crosstalk between fat and muscle in overweight/obesity. Diabetologia. 2013;56(10):2275‐2285. doi:10.1007/s00125‐013‐2996‐8.
Chen X, Tian F, Sun Z, Zeng G, Tang P. Elevation of circulating miR‐210 participates in the occurrence and development of type 2 diabetes mellitus and its complications. J Diabetes Res. 2022;2022:9611509. doi:10.1155/2022/9611509.
Yang P, Dong X, Zhang Y. MicroRNA profiles in plasma samples from young metabolically healthy obese patients and miRNA‐21 are associated with diastolic dysfunction via TGF‐beta 1/Smad pathway. J Clin Lab Anal. 2020;34(6):e23246. doi:10.1002/jcla.23246.
Xu Q, Li Y, Shang Y‐F, Wang H‐L, Yao M‐X. miRNA‐103: molecular link between insulin resistance and nonalcoholic fatty liver disease. World J Gastroenterol. 2015;21(2):511‐516. doi:10.3748/wjg.v21.i2.511.
Li F, Zhang K, Xu T, et al. Exosomal microRNA‐29a mediates cardiac dysfunction and mitochondrial inactivity in obesity‐related cardiomyopathy. Endocrine. 2019;63(3):480‐488. doi:10.1007/s12020‐018‐1753‐7.
Bao F, Slusher AL, Whitehurst M, Huang CJ. Circulating microRNAs are upregulated following acute aerobic exercise in obese individuals. Physiol Behav. 2018;197:15‐21. doi:10.1016/j.physbeh.2018.09.011.
Goguet‐Rubio P, Klug RL, Sharma DL, et al. Existence of a strong correlation of biomarkers and miRNA in females with metabolic syndrome and obesity in a population of West Virginia. Int J Med Sci. 2017;14(6):543‐553. doi:10.7150/ijms.18988.
Williams A, Mc Dougal D, Jenkins W, Greene N, Williams‐DeVane C, Kimbro KS. Serum miR‐17 levels are downregulated in obese, African American women with elevated HbA1c. J Diabetes Metab Disord. 2019;18(1):173‐179. doi:10.1007/s40200‐019‐00404‐3.
Benbaibeche H, Hichami A, Oudjit B, et al. Circulating mir‐21 and mir‐146a are associated with increased cytokines and CD36 in Algerian obese male participants. Arch Physiol Biochem. 2022;128(6):1461‐1466. doi:10.1080/13813455.2020.1775655.
Vonhogen IGC, Mohseni Z, Winkens B, et al. Circulating miR‐216a as a biomarker of metabolic alterations and obesity in women. Non‐Coding Rna Res. 2020;5(3):144‐152. doi:10.1016/j.ncrna.2020.08.001.
Li D, Song H, Shuo L, et al. Gonadal white adipose tissue‐derived exosomal MiR‐222 promotes obesity‐associated insulin resistance. Aging. 2020;12(22):22719‐22743. doi:10.18632/aging.103891.
Refeat MM, Hassan NA‐M, Ahmad IH, Mostafa ERM, Amr KS. Correlation of circulating miRNA‐33a and miRNA‐122 with lipid metabolism among Egyptian patients with metabolic syndrome. J Genet Eng Biotechnol. 2021;19(1):147. doi:10.1186/s43141‐021‐00246‐8.
Abd El‐Jawad AM, Ibrahim IH, Zaki ME, Elias TR, Rasheed WI, Amr KS. The potential role of miR‐27a and miR‐320a in metabolic syndrome in obese Egyptian females. J Genet Eng Biotechnol. 2022;20(1):75. doi:10.1186/s43141‐022‐00348‐x.
Ghorbani S, Mahdavi R, Alipoor B, et al. Decreased serum microRNA‐21 level is associated with obesity in healthy and type 2 diabetic subjects. Arch Physiol Biochem. 2018;124(4):300‐305. doi:10.1080/13813455.2017.1396349.
Heneghan HM, Miller N, McAnena OJ, O'Brien T, Kerin MJ. Differential miRNA expression in omental adipose tissue and in the circulation of obese patients identifies novel metabolic biomarkers. J Clin Endocrinol Metab. 2011;96(5):E846‐E850. doi:10.1210/jc.2010‐2701.
Kilic ID, Dodurga Y, Uludag B, et al. microRNA‐143 and‐223 in obesity. Gene. 2015;560(2):140‐142. doi:10.1016/j.gene.2015.01.048.
Russo A, Bartolini D, Mensà E, et al. Physical activity modulates the overexpression of the inflammatory miR‐146a‐5p in obese patients. IUBMB Life. 2018;70(10):1012‐1022. doi:10.1002/iub.1926.
Abu‐Farha M, Cherian P, Al‐Khairi I, et al. Reduced miR‐181d level in obesity and its role in lipid metabolism via regulation of ANGPTL3. Sci Rep. 2019;9(1):9. doi:10.1038/s41598‐019‐48371‐2.
Bellae Papannarao J, Schwenke DO, Manning P, Katare R. Upregulated miR‐200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity. Int J Obes (Lond). 2022;46(1):238‐241. doi:10.1038/s41366‐021‐00984‐2.
Wen D, Qiao P, Wang L. Circulating microRNA‐223 as a potential biomarker for obesity. Obes Res Clin Pract. 2015;9(4):398‐404. doi:10.1016/j.orcp.2015.01.006.
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Med: J Br Diabetic Assoc. 1998;15(7):539‐553. doi:10.1002/(SICI)1096‐9136(199807)15:7<539::AID‐DIA668>3.0.CO;2‐S.
Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143‐3421. doi:10.1161/circ.106.25.3143.
Zheng Z, Liu L, Zhan Y, Yu S, Kang T. Adipose‐derived stem cell‐derived microvesicle‐released miR‐210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3. Cell Cycle. 2018;17(8):1026‐1033. doi:10.1080/15384101.2018.1480207.
Kang T, Jones TM, Naddell C, et al. Adipose‐derived stem cells induce angiogenesis via microvesicle transport of miRNA‐31. Stem Cells Transl Med. 2016;5(4):440‐450. doi:10.5966/sctm.2015‐0177.
Voynova E, Kulebyakin K, Grigorieva O, et al. Declined adipogenic potential of senescent MSCs due to shift in insulin signaling and altered exosome cargo. Front Cell Dev Biol. 2022;10:10. doi:10.3389/fcell.2022.1050489.
Pi L, Yang L, Fang BR, Meng XX, Qian L. Exosomal microRNA‐125a‐3p from human adipose‐derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN. Mol Cell Biochem. 2022;477(1):115‐127. doi:10.1007/s11010‐021‐04251‐w.
Zhu D, Wang Y, Thomas M, et al. Exosomes from adipose‐derived stem cells alleviate myocardial infarction via microRNA‐31/FIH1/HIF‐1α pathway. J Mol Cell Cardiol. 2022;162:10‐19. doi:10.1016/j.yjmcc.2021.08.010.
Reza AMMT, Choi Y‐J, Yasuda H, Kim J‐H. Human adipose mesenchymal stem cell‐derived exosomal‐miRNAs are critical factors for inducing anti‐proliferation signalling to A2780 and SKOV‐3 ovarian cancer cells. Sci Rep. 2016;6(1):6. doi:10.1038/srep38498.
Heo JS, Kim S, Yang CE, Choi Y, Song SY, Kim HO. Human adipose mesenchymal stem cell‐derived exosomes: a key player in wound healing. Tissue Eng Regener Med. 2021;18(4):537‐548. doi:10.1007/s13770‐020‐00316‐x.
Cao G, Chen B, Zhang X, Chen H. Human adipose‐derived mesenchymal stem cells‐derived Exosomal microRNA‐19b promotes the healing of skin wounds through modulation of the CCL1/TGF‐β signaling Axis. Clin Cosmetic Investigational Dermatol. 2020;13:957‐971. doi:10.2147/CCID.S274370.
Huang B, Huang L‐F, Zhao L, et al. Microvesicles (MIVs) secreted from adipose‐derived stem cells (ADSCs) contain multiple microRNAs and promote the migration and invasion of endothelial cells. Genes Dis. 2020;7(2):225‐234. doi:10.1016/j.gendis.2019.04.005.
Ragni E, Orfei CP, De Luca P, et al. miR‐22‐5p and miR‐29a‐5p are reliable reference genes for analyzing extracellular vesicle‐associated miRNAs in adipose‐derived mesenchymal stem cells and are stable under inflammatory priming mimicking osteoarthritis condition. Stem Cell Rev Rep. 2019;15(5):743‐754. doi:10.1007/s12015‐019‐09899‐y.
Liu Y, Tan J, Ou S, Chen J, Chen L. Adipose‐derived exosomes deliver miR‐23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis. J Physiol Biochem. 2019;75(3):391‐401. doi:10.1007/s13105‐019‐00692‐6.
Alicka M, Major P, Wysocki M, Marycz K. Adipose‐derived mesenchymal stem cells isolated from patients with type 2 diabetes show reduced "Stemness" through an altered Secretome profile, impaired anti‐oxidative protection, and mitochondrial dynamics deterioration. J Clin Med. 2019;8(6):765. doi:10.3390/jcm8060765.
Yang Z, Wei Z, Wu X, Yang H. Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: determination of targets for the treatment of obesity and associated metabolic disorders. Mol Med Rep. 2018;18(3):3314‐3324. doi:10.3892/mmr.2018.9312.
Li F, Xu Z, Xie Z, et al. Adipose mesenchymal stem cells‐derived exosomes alleviate osteoarthritis by transporting microRNA ‐376c‐3p and targeting the WNT‐beta‐catenin signaling axis. Apoptosis. 2022;28(3‐4):362‐378. doi:10.1007/s10495‐022‐01787‐0.
Xu F, Xiang Q, Huang J, et al. Exosomal miR‐423‐5p mediates the proangiogenic activity of human adipose‐derived stem cells by targeting Sufu. Stem Cell Res Ther. 2019;10(1):10. doi:10.1186/s13287‐019‐1196‐y.
Li Y, Zhang J, Shi J, et al. Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR‐192‐5p/IL‐17RA/Smad axis. Stem Cell Res Ther. 2021;12(1):12. doi:10.1186/s13287‐021‐02290‐0.
Yang W, Tu H, Tang K, Huang H, Ou S, Wu J. MiR‐3064 in Epicardial adipose‐derived exosomes targets Neuronatin to regulate Adipogenic differentiation of Epicardial adipose stem cells. Front Cardiovasc Med. 2021;8:8. doi:10.3389/fcvm.2021.709079.
Seo M, Kim SM, Woo EY, et al. Stemness‐attenuating miR‐503‐3p as a paracrine factor to regulate growth of cancer stem cells. Stem Cells Int. 2018;2018:4851949. doi:10.1155/2018/4851949.
García‐Contreras M, Vera‐Donoso CD, Hernández‐Andreu JM, García‐Verdugo JM, Oltra E. Therapeutic potential of human adipose‐derived stem cells (ADSCs) from cancer patients: a pilot study. PLoS ONE. 2014;9(11):e113288. doi:10.1371/journal.pone.0113288.
Mahdavi R, Ghorbani S, Alipoor B, et al. Decreased serum level of miR‐155 is associated with obesity and its related metabolic traits. Clin Lab. 2018;64(1):77‐84. doi:10.7754/Clin.Lab.2017.170618.
Sangiao‐Alvarellos S, Theofilatos K, Barwari T, et al. Metabolic recovery after weight loss surgery is reflected in serum microRNAs. BMJ Open Diabetes Res Care. 2020;8(2):8. doi:10.1136/bmjdrc‐2020‐001441.
Lozano‐Bartolomé J, Llauradó G , Portero‐Otin M, et al. Altered expression of miR‐181a‐5p and miR‐23a‐3p is associated with obesity and TNFα‐induced insulin resistance. J Clin Endocrinol Metab. 2018; 103: 1447‐1458. doi: 10.1210/jc.2017‐01909.
Xiong J, Liu Z, Wu M, Sun M, Xia Y, Wang Y. Comparison of proangiogenic effects of adipose‐derived stem cells and foreskin fibroblast exosomes on artificial dermis prefabricated flaps. Stem Cells Int. 2020;2020:5293850. doi:10.1155/2020/5293850.
Fu J, Niu H, Gao G, et al. Naringenin promotes angiogenesis of ischemic myocardium after myocardial infarction through miR‐223‐3p/IGF1R axis. Regener Ther. 2022;21:362‐371. doi:10.1016/j.reth.2022.07.008.
Rui L, Liu R, Jiang H, Liu K. Sox9 promotes cardiomyocyte apoptosis after acute myocardial infarction by promoting miR‐223‐3p and inhibiting MEF2C. Mol Biotechnol. 2022;64(8):902‐913. doi:10.1007/s12033‐022‐00471‐7.
Chen C, Cai S, Wu M, et al. Role of cardiomyocyte‐derived Exosomal MicroRNA‐146a‐5p in macrophage polarization and activation. Dis Markers. 2022;2022:2948578. doi:10.1155/2022/2948578.
Song S, Seo HH, Lee SY, et al. MicroRNA‐17‐mediated down‐regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes. Biochem Biophys Res Commun. 2015;465(2):299‐304. doi:10.1016/j.bbrc.2015.08.028.
Li J, Tong Y, Zhou Y, et al. LncRNA KCNQ1OT1 as a miR‐26a‐5p sponge regulates ATG12‐mediated cardiomyocyte autophagy and aggravates myocardial infarction. Int J Cardiol. 2021;338:14‐23. doi:10.1016/j.ijcard.2021.05.053.
Xin H, Li C, Cai T, Cao J, Wang M. LncRNA KCNQ1OT1 contributes to hydrogen peroxide‐induced apoptosis, inflammation, and oxidative stress of cardiomyocytes via miR‐130a‐3p/ZNF791 axis. Cell Biol Int. 2022;46(12):2018‐2027. doi:10.1002/cbin.11873.
Zhou T, Qin G, Yang L, Xiang D, Li S. LncRNA XIST regulates myocardial infarction by targeting miR‐130a‐3p. J Cell Physiol. 2019;234(6):8659‐8667. doi:10.1002/jcp.26327.
Liu R, Zhang H, Wang X, et al. The miR‐24‐Bim pathway promotes tumor growth and angiogenesis in pancreatic carcinoma. Oncotarget. 2015;6:43831‐42. doi: 10.18632/oncotarget.6257.
Izarra A, Moscoso I, Levent E, et al. miR‐133a enhances the protective capacity of cardiac progenitors cells after myocardial infarction. Stem Cell Rrep. 2014;3(6):1029‐1042. doi:10.1016/j.stemcr.2014.10.010.
Chen HY, Lu J, Wang ZK, et al. Hsa‐miR‐199a‐5p protect cell injury in hypoxia induces myocardial cells via targeting HIF1α. Mol Biotechnol. 2022;64(5):482‐492. doi:10.1007/s12033‐021‐00423‐7.
Li Q, Xie J, Li R, et al. Overexpression of microRNA‐99a attenuates heart remodelling and improves cardiac performance after myocardial infarction. J Cell Mol Med. 2014;18(5):919‐928. doi:10.1111/jcmm.12242.
Wu L, Chen Y, Chen Y, et al. Effect of HIF‐1α/miR‐10b‐5p/PTEN on hypoxia‐induced cardiomyocyte apoptosis. J am Heart Assoc. 2019;8(18):e011948. doi:10.1161/JAHA.119.011948.
Gao ZF, Ji XL, Gu J, Wang XY, Ding L, Zhang H. microRNA‐107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1‐dependent notch signaling pathway in a mouse model of coronary atherosclerosis. J Cell Physiol. 2019;234(7):12029‐12041. doi:10.1002/jcp.27864.
Zhang Y, Zhang C, Chen Z, Wang M. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis. Open Life Sci. 2021;16(1):419‐430. doi:10.1515/biol‐2021‐0044.
Feng Z, Zhu Y, Zhang J, Yang W, Chen Z, Li B. Hsa‐circ_0010283 regulates oxidized low‐density lipoprotein‐induced proliferation and migration of vascular smooth muscle cells by targeting the miR‐133a‐3p/pregnancy‐associated plasma protein a Axis. Circulation J. 2020;84(12):2259‐2269. doi:10.1253/circj.CJ‐20‐0345.
Zhou Y, Ma W, Bian H, et al. Long non‐coding RNA MIAT/miR‐148b/PAPPA axis modifies cell proliferation and migration in ox‐LDL‐induced human aorta vascular smooth muscle cells. Life Sci. 2020;256:117852. doi:10.1016/j.lfs.2020.117852.
Wang J, Xu X, Li P, Zhang B, Zhang J. HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA‐19b/PPARγ/NF‐κB axis. Atherosclerosis. 2021;323:1‐12. doi:10.1016/j.atherosclerosis.2021.02.013.
Zhang Y, Wang L, Xu J, Kong X, Zou L. Up‐regulated miR‐106b inhibits ox‐LDL‐induced endothelial cell apoptosis in atherosclerosis. Braz J Med Biol Res = Revista brasileira de pesquisas medicas e biologicas. 2020;53(3):e8960. doi:10.1590/1414‐431x20198960.
Liang W, Chen J, Zheng H, et al. MiR‐199a‐5p‐containing macrophage‐derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis. Cell Biol Toxicol. 2022;39(3):591‐605. doi:10.1007/s10565‐022‐09732‐2.
Hu Y, Peng X, Du G, et al. MicroRNA‐122‐5p inhibition improves inflammation and oxidative stress damage in dietary‐induced non‐alcoholic fatty liver disease through targeting FOXO3. Front Physiol. 2022;13:803445. doi:10.3389/fphys.2022.803445.
Wang X, Ma Y, Yang LY, Zhao D. MicroRNA‐20a‐5p ameliorates non‐alcoholic fatty liver disease via inhibiting the expression of CD36. Front Cell Dev Biol. 2020;8:596329. doi:10.3389/fcell.2020.596329.
Du X, Li H, Han X, Ma W. Mesenchymal stem cells‐derived exosomal miR‐24‐3p ameliorates non‐alcohol fatty liver disease by targeting Keap‐1. Biochem Biophys Res Commun. 2022;637:331‐340. doi:10.1016/j.bbrc.2022.11.012.
Singh R, Ha SE, Wei L, et al. miR‐10b‐5p rescues diabetes and gastrointestinal Dysmotility. Gastroenterology. 2021;160(5):1662‐78.e18. doi:10.1053/j.gastro.2020.12.062.
Song J, He Q, Guo X, et al. Mesenchymal stem cell‐conditioned medium alleviates high fat‐induced hyperglucagonemia via miR‐181a‐5p and its target PTEN/AKT signaling. Mol Cell Endocrinol. 2021;537:111445. doi:10.1016/j.mce.2021.111445.
Zhang S, Liu X, Wang J, Yuan F, Liu Y. Targeting ferroptosis with miR‐144‐3p to attenuate pancreatic β cells dysfunction via regulating USP22/SIRT1 in type 2 diabetes. Diabetol Metab Syndr. 2022;14(1):89. doi:10.1186/s13098‐022‐00852‐7.
Chen Z, Pan X, Sheng Z, Yan G, Chen L, Ma G. miR‐17 regulates the proliferation and apoptosis of endothelial cells in coronary heart disease via targeting insulin‐like‐growth factor 1. Pathol Res Pract. 2019;215(9):152512. doi:10.1016/j.prp.2019.152512.
Guo Y, Liu Z, Wang M. NFKB1‐mediated downregulation of microRNA‐106a promotes oxidative stress injury and insulin resistance in mice with gestational hypertension. Cytotechnology. 2021;73(1):115‐126. doi:10.1007/s10616‐020‐00448‐x.
Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100(10):1134‐1146. doi:10.1161/01.CIR.100.10.1134.
Lo CH, Li LC, Yang SF, et al. MicroRNA let‐7a, −7e and ‐133a attenuate hypoxia‐induced atrial fibrosis via targeting collagen expression and the JNK pathway in HL1 cardiomyocytes. Int J Mol Sci. 2022;23(17):23. doi:10.3390/ijms23179636.
Samuel VT, Shulman GI. Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases. Cell Metab. 2018;27(1):22‐41. doi:10.1016/j.cmet.2017.08.002.
Gjorgjieva M, Sobolewski C, Dolicka D, Correia de Sousa M, Foti M. miRNAs and NAFLD: from pathophysiology to therapy. Gut. 2019;68(11):2065‐2079. doi:10.1136/gutjnl‐2018‐318146.
Li J, Qi J, Tang Y, et al. A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR‐106a‐5p/miR‐320a and ABCA1/CPT1 axis. J Nanobiotechnol. 2021;19(1):363. doi:10.1186/s12951‐021‐01108‐8.
Niu Q, Wang T, Wang Z, et al. Adipose‐derived mesenchymal stem cell‐secreted extracellular vesicles alleviate non‐alcoholic fatty liver disease via delivering miR‐223‐3p. Adipocyte. 2022;11(1):572‐587. doi:10.1080/21623945.2022.2098583.
Wang Y, Du J, Niu X, et al. MiR‐130a‐3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2. Cell Death Dis. 2017;8(5):e2792. doi:10.1038/cddis.2017.10.
Du J, Niu X, Wang Y, et al. MiR‐146a‐5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a. Sci Rep. 2015;5(1):16163. doi:10.1038/srep16163.
Jampoka K, Muangpaisarn P, Khongnomnan K, Treeprasertsuk S, Tangkijvanich P, Payungporn S. Serum miR‐29a and miR‐122 as potential biomarkers for non‐alcoholic fatty liver disease (NAFLD). MicroRNA (Shariqah, United Arab Emirates). 2018;7(3):215‐222. doi:10.2174/2211536607666180531093302.
Ye D, Zhang T, Lou G, et al. Plasma miR‐17, miR‐20a, miR‐20b and miR‐122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients. Life Sci. 2018;208:201‐207. doi:10.1016/j.lfs.2018.07.029.
Hattori Y, Yamada H, Munetsuna E, et al. The ratio of miR‐122 to miR‐20a (miR‐122/miR‐20a) is a useful minimally invasive biomarker for non‐alcoholic fatty liver disease detection. Genet Test Mol Biomarkers. 2023;27(8):239‐247. doi:10.1089/gtmb.2022.0155.
Ju C, Wang M, Tak E, et al. Hypoxia‐inducible factor‐1α‐dependent induction of miR122 enhances hepatic ischemia tolerance. J Clin Invest. 2021;131(7):e140300. doi:10.1172/JCI140300.
Hochreuter MY, Dall M, Treebak JT, Barrès R. MicroRNAs in non‐alcoholic fatty liver disease: Progress and perspectives. Mol Metab. 2022;65:101581. doi:10.1016/j.molmet.2022.101581.
Yang L, Liu Q, Zhang H, et al. Silibinin improves nonalcoholic fatty liver by regulating the expression of miR‐122: an in vitro and in vivo study. Mol Med Rep. 2021;23. doi: 10.3892/mmr.2021.11974.
Karimi‐Sales E, Jeddi S, Ebrahimi‐Kalan A, Alipour MR. Protective role of trans‐Chalcone against the progression from simple steatosis to non‐alcoholic steatohepatitis: regulation of miR‐122, 21, 34a, and 451. Adv Pharm Bull. 2022;12(1):200‐205. doi:10.34172/apb.2022.022.
Liu H, Wang X, Wang ZY, Li L. Circ_0080425 inhibits cell proliferation and fibrosis in diabetic nephropathy via sponging miR‐24‐3p and targeting fibroblast growth factor 11. J Cell Physiol. 2020;235(5):4520‐4529. doi:10.1002/jcp.29329.
He X, Zeng X. LncRNA SNHG16 aggravates high glucose‐induced podocytes injury in diabetic nephropathy through targeting miR‐106a and thereby up‐regulating KLF9. Diabetes Metab Syndr Obes: Targets Ther. 2020;13:3551‐3560. doi:10.2147/DMSO.S271290.
Feng F, Yang J, Wang G, Huang P, Li Y, Zhou B. Circ_0068087 promotes high glucose‐induced human renal tubular cell injury through regulating miR‐106a‐5p/ROCK2 pathway. Nephron. 2022;1‐11(3‐4):212‐222. doi:10.1159/000525440.
Yuan Y, Li X, Li M. Overexpression of miR‐17‐5p protects against high glucose‐induced endothelial cell injury by targeting E2F1‐mediated suppression of autophagy and promotion of apoptosis. Int J Mol Med. 2018;42(3):1559‐1568. doi:10.3892/ijmm.2018.3697.
Cui YX, Hua YZ, Wang N, et al. miR‐24 suppression of POZ/BTB and AT‐hook‐containing zinc finger protein 1 (PATZ1) protects endothelial cell from diabetic damage. Biochem Biophys Res Commun. 2016;480(4):682‐689. doi:10.1016/j.bbrc.2016.10.116.
Tong M, Saito T, Zhai P, et al. Mitophagy is essential for maintaining cardiac function during high fat diet‐induced diabetic cardiomyopathy. Circ Res. 2019;124(9):1360‐1371. doi:10.1161/CIRCRESAHA.118.314607.
Kuma A, Komatsu M, Mizushima N. Autophagy‐monitoring and autophagy‐deficient mice. Autophagy. 2017;13(10):1619‐1628. doi:10.1080/15548627.2017.1343770.
Lim YM, Lim H, Hur KY, et al. Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes. Nat Commun. 2014;5(1):4934. doi:10.1038/ncomms5934.
Settembre C, De Cegli R, Mansueto G, et al. TFEB controls cellular lipid metabolism through a starvation‐induced autoregulatory loop. Nat Cell Biol. 2013;15(6):647‐658. doi:10.1038/ncb2718.
Yang L, Li P, Fu S, Calay ES, Hotamisligil GS. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab. 2010;11(6):467‐478. doi:10.1016/j.cmet.2010.04.005.
Kim KH, Jeong YT, Oh H, et al. Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine. Nat Med. 2013;19(1):83‐92. doi:10.1038/nm.3014.
Jiang P, Du W, Wang X, et al. p53 regulates biosynthesis through direct inactivation of glucose‐6‐phosphate dehydrogenase. Nat Cell Biol. 2011;13(3):310‐316. doi:10.1038/ncb2172.
Bensaad K, Tsuruta A, Selak MA, et al. TIGAR, a p53‐inducible regulator of glycolysis and apoptosis. Cell. 2006;126(1):107‐120. doi:10.1016/j.cell.2006.05.036.
Park JY, Wang PY, Matsumoto T, et al. p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res. 2009;105(7):705‐712, 11 p following 12. doi:10.1161/CIRCRESAHA.109.205310.
Kitamura N, Nakamura Y, Miyamoto Y, et al. Mieap, a p53‐inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. PLoS ONE. 2011;6(1):e16060. doi:10.1371/journal.pone.0016060.
Yahagi N, Shimano H, Matsuzaka T, et al. p53 involvement in the pathogenesis of fatty liver disease. J Biol Chem. 2004;279(20):20571‐20575. doi:10.1074/jbc.M400884200.
Shimizu I, Yoshida Y, Katsuno T, et al. p53‐induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab. 2012;15(1):51‐64. doi:10.1016/j.cmet.2011.12.006.
Minamino T, Orimo M, Shimizu I, et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009;15(9):1082‐1087. doi:10.1038/nm.2014.
Chu DT, Tao Y. Molecular connections of obesity and aging: a focus on adipose protein 53 and retinoblastoma protein. Biogerontology. 2017;18(3):321‐332. doi:10.1007/s10522‐017‐9698‐4.
Lee YS, Li P, Huh JY, et al. Inflammation is necessary for long‐term but not short‐term high‐fat diet‐induced insulin resistance. Diabetes. 2011;60(10):2474‐2483. doi:10.2337/db11‐0194.
Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72(1):219‐246. doi:10.1146/annurev‐physiol‐021909‐135846.
Schwartz C, Schmidt V, Deinzer A, et al. Innate PD‐L1 limits T cell‐mediated adipose tissue inflammation and ameliorates diet‐induced obesity. Sci Transl Med. 2022;14(635):eabj6879. doi:10.1126/scitranslmed.abj6879.
Turbitt WJ, Buchta Rosean C, Weber KS, Norian LA. Obesity and CD8 T cell metabolism: implications for anti‐tumor immunity and cancer immunotherapy outcomes. Immunol Rev. 2020;295(1):203‐219. doi:10.1111/imr.12849.
Karshovska E, Wei Y, Subramanian P, et al. HIF‐1α (hypoxia‐inducible factor‐1α) promotes macrophage necroptosis by regulating miR‐210 and miR‐383. Arterioscler Thromb Vasc Biol. 2020;40(3):583‐596. doi:10.1161/ATVBAHA.119.313290.
Moszyńska A, Jaśkiewicz M, Serocki M, et al. The hypoxia‐induced changes in miRNA‐mRNA in RNA‐induced silencing complexes and HIF‐2 induced miRNAs in human endothelial cells. FASEB j. 2022;36(7):e22412. doi:10.1096/fj.202101987R.
Wu R, Zeng J, Yuan J, et al. MicroRNA‐210 overexpression promotes psoriasis‐like inflammation by inducing Th1 and Th17 cell differentiation. J Clin Invest. 2018;128(6):2551‐2568. doi:10.1172/JCI97426.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796‐1808. doi:10.1172/JCI200319246.
Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity‐related insulin resistance. J Clin Invest. 2003;112(12):1821‐1830. doi:10.1172/JCI200319451.
Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nat Rev Mol Cell Biol. 2019;20(4):242‐258. doi:10.1038/s41580‐018‐0093‐z.
John E, Wienecke‐Baldacchino A, Liivrand M, Heinäniemi M, Carlberg C, Sinkkonen L. Dataset integration identifies transcriptional regulation of microRNA genes by PPARγ in differentiating mouse 3T3‐L1 adipocytes. Nucleic Acids Res. 2012;40(10):4446‐4460. doi:10.1093/nar/gks025.
Ouyang D, Xu L, Zhang L, et al. MiR‐181a‐5p regulates 3T3‐L1 cell adipogenesis by targeting Smad7 and Tcf7l2. Acta Biochim Biophys Sin. 2016;48(11):1034‐1041. doi:10.1093/abbs/gmw100.
Pan JA, Lin H, Yu JY, et al. MiR‐21‐3p inhibits adipose Browning by targeting FGFR1 and aggravates atrial fibrosis in diabetes. Oxid Med Cell Longev. 2021;2021:9987219. doi:10.1155/2021/9987219.
McClure C, McPeak MB, Youssef D, Yao ZQ, McCall CE, El Gazzar M. Stat3 and C/EBPβ synergize to induce miR‐21 and miR‐181b expression during sepsis. Immunol Cell Biol. 2017;95(1):42‐55. doi:10.1038/icb.2016.63.

2023JH2/101600009 Application Foundation Plan of Liaoning Science and Technology Department; 2022JH1/10400001 "Announce the List and Take Charge" Major Scientific and Technological Projects of Liaoning Province; 82000827 National Natural Science Foundation of China; 82204025 National Natural Science Foundation of China

Keywords: adipose tissue; circulating miRNAs; comorbidity; obesity

0 (MicroRNAs)
0 (Biomarkers)

Date Created: 20240409 Date Completed: 20240607 Latest Revision: 20240613

20240613

10.1111/obr.13748

38590187