Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

MicroRNA-132 may be associated with blood pressure and liver steatosis—preliminary observations in obese individuals

Journal of Human Hypertension volume 36, pages 911–916 (2022)Cite this article

Subjects

Abstract

Recent findings in experimental models have shown that the microRNA miR-132 (mir-132) is an important regulator of liver homeostasis and lipid metabolism. We aimed to assess miR-132 expression in liver and fat tissues of obese individuals and examine its association with blood pressure (BP) and hepatic steatosis. We examined obese individuals undergoing bariatric surgery for weight loss (n = 19). Clinical and demographic information was obtained. Quantitative PCR was performed to determine tissue expression of miR-132 in liver and subcutaneous and visceral fat biopsies obtained during bariatric surgery. Liver biopsies were read by a single liver pathologist and graded for steatosis, inflammation and fibrosis. Participants (aged 39 ± 8.1 years) had a body mass index (BMI) of 42 ± 4.5 kg/m2 and presented with 2.2 ± 1.2 metabolic abnormalities. Supine BP was 127 ± 16/74 ± 11 mmHg. Hepatic and visceral fat expression of miR-132 were correlated (r = 0.59, P = 0.033). There was no correlation between subcutaneous and visceral expression of miR-132 (r = −0.31, P = 0.20). Hepatic and visceral fat miR-132 expression were associated with BMI (r = 0.62 and r = 0.68, P = 0.049 respectively) and degree of liver steatosis (r = 0.60 and r = 0.55, P < 0.05, respectively). Subcutaneous fat miRNA-132 expression was correlated to office systolic BP (r = 0.46, P < 0.05), several aspects of 24 h BP (24 h systolic BP: r = 0.52; day systolic BP: r = 0.59, P < 0.05 for all), plasma triglycerides (r = 0.51, P < 0.01) and liver enzymes (ALT: r = −0.52; AST: r = −0.48, P < 0.05 for all). We found an association between miR-132 and markers of cardiovascular and metabolic disease. Reduction of miR-132 may be a target for the regulation of liver lipid homeostasis and control of obesity-related blood pressure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Association between body mass index and miRNA-132 expression.

Similar content being viewed by others

References

  1. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–85.

    Article  CAS  Google Scholar 

  2. Mokdad AA, Lopez AD, Shahraz S, Lozano R, Mokdad AH, Stanaway J, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12:145.

    Article  Google Scholar 

  3. Calzadilla Bertot L, Adams LA. The natural course of non-alcoholic fatty liver disease. Int J Mol Sci. 2016;17:774. https://doi.org/10.3390/ijms17050774.

  4. Hanin G, Yayon N, Tzur Y, Haviv R, Bennett ER, Udi S, et al. miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression. Gut. 2018;67:1124–34.

    Article  CAS  Google Scholar 

  5. Jin J, Iakova P, Breaux M, Sullivan E, Jawanmardi N, Chen D, et al. Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis. Cell Rep. 2013;3:831–43.

    Article  CAS  Google Scholar 

  6. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327–38.

    Article  CAS  Google Scholar 

  7. Stiles B, Wang Y, Stahl A, Bassilian S, Lee WP, Kim YJ, et al. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity. Proc Natl Acad Sci USA. 2004;101:2082–7.

    Article  CAS  Google Scholar 

  8. Strum JC, Johnson JH, Ward J, Xie H, Feild J, Hester A, et al. MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1. Mol Endocrinol. 2009;23:1876–84.

    Article  CAS  Google Scholar 

  9. van Zonneveld AJ, Au YW, Stam W, van Gelderen S, Rotmans JI, Deen PMT, et al. MicroRNA-132 regulates salt-dependent steady-state renin levels in mice. Commun Biol. 2020;3:238.

    Article  Google Scholar 

  10. Eskildsen TV, Jeppesen PL, Schneider M, Nossent AY, Sandberg MB, Hansen PB, et al. Angiotensin II regulates microRNA-132/-212 in hypertensive rats and humans. Int J Mol Sci. 2013;14:11190–207.

    Article  Google Scholar 

  11. Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, et al. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat Commun. 2012;3:1078.

    Article  Google Scholar 

  12. Masson S, Batkai S, Beermann J, Bar C, Pfanne A, Thum S, et al. Circulating microRNA-132 levels improve risk prediction for heart failure hospitalization in patients with chronic heart failure. Eur J Heart Fail. 2018;20:78–85.

    Article  CAS  Google Scholar 

  13. Lambert EA, Rice T, Eikelis N, Straznicky NE, Lambert GW, Head GA, et al. Sympathetic activity and markers of cardiovascular risk in nondiabetic severely obese patients: the effect of the initial 10% weight loss. Am J Hypertens. 2014;27:1308–15.

    Article  CAS  Google Scholar 

  14. Dixon JB, Bhathal PS, O’Brien PE. Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg. 2006;16:1278–86.

    Article  Google Scholar 

  15. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–21.

    Article  Google Scholar 

  16. Mangiafico SS. Summary and Analysis of Extension Program Evaluation in R, version 1.18.8. 2016. rcompanion.org/handbook/. (Pdf version: rcompanion.org/documents/RHandbookProgramEvaluation.pdf.

  17. Core Team R. R: a language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria, 2019. https://www.R-project.org.

  18. Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2:231–7.

    Article  CAS  Google Scholar 

  19. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, et al. MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med. 2010;16:909–14.

    Article  CAS  Google Scholar 

  20. Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, et al. MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity. 2009;31:965–73.

  21. Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998;47:913–7.

    Article  Google Scholar 

  22. Eikelis N, Esler M, Barton D, Dawood T, Wiesner G, Lambert G. Reduced brain leptin in patients with major depressive disorder and in suicide victims. Mol Psychiatry. 2006;11:800–1.

    Article  CAS  Google Scholar 

  23. Eikelis N, Lambert G, Wiesner G, Kaye D, Schlaich M, Morris M, et al. Extra-adipocyte leptin release in human obesity and its relation to sympathoadrenal function. Am J Physiol Endocrinol Metab. 2004;286:E744–52.

    Article  CAS  Google Scholar 

  24. Byrne CD. Ectopic fat, insulin resistance and non-alcoholic fatty liver disease. Proc Nutr Soc. 2013;72:412–9.

    Article  CAS  Google Scholar 

  25. Donati G, Stagni B, Piscaglia F, Venturoli N, Morselli-Labate AM, Rasciti L, et al. Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut. 2004;53:1020–3.

    Article  CAS  Google Scholar 

  26. Gutierrez-Buey G, Nunez-Cordoba JM, Llavero-Valero M, Gargallo J, Salvador J, Escalada J. Is HOMA-IR a potential screening test for non-alcoholic fatty liver disease in adults with type 2 diabetes? Eur J Intern Med. 2017;41:74–8.

    Article  CAS  Google Scholar 

  27. Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C. Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol. 2011;17:3082–91.

    PubMed  PubMed Central  Google Scholar 

  28. Ni YG, Berenji K, Wang N, Oh M, Sachan N, Dey A, et al. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation. 2006;114:1159–68.

    Article  CAS  Google Scholar 

  29. Liu X, Tong Z, Chen K, Hu X, Jin H, Hou M. The Role of miRNA-132 against apoptosis and oxidative stress in heart failure. Biomed Res Int. 2018;2018:3452748.

    PubMed  PubMed Central  Google Scholar 

  30. Zhang L, Huang D, Wang Q, Shen D, Wang Y, Chen B, et al. MiR-132 inhibits expression of SIRT1 and induces pro-inflammatory processes of vascular endothelial inflammation through blockade of the SREBP-1c metabolic pathway. Cardiovasc Drugs Ther. 2014;28:303–11.

    Article  CAS  Google Scholar 

  31. Eikelis N, Marques FZ, Hering D, Marusic P, Head GA, Walton AS, et al. A polymorphism in the noradrenaline transporter gene is associated with increased blood pressure in patients with resistant hypertension. J Hypertens. 2018;36:1571–7.

    Article  CAS  Google Scholar 

  32. Marques FZ, Eikelis N, Bayles RG, Lambert EA, Straznicky NE, Hering D, et al. A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism. Mol Psychiatry. 2017;22:134–41.

    Article  CAS  Google Scholar 

  33. Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3:87–98.

    Article  CAS  Google Scholar 

  34. Rottiers V, Naar AM. MicroRNAs in metabolism and metabolic disorders. Nat Rev Mol Cell Biol. 2012;13:239–50.

    Article  CAS  Google Scholar 

  35. Winkle M, El-Daly SM, Fabbri M, Calin GA. Noncoding RNA therapeutics—challenges and potential solutions. Nat Rev Drug Discov. 2021;20:629–65.

Download references

Acknowledgements

Supported in part by funding from the National Health and Medical Research Council of Australia (NHMRC), Swinburne Research at Swinburne University of Technology, the Victorian Government’s Operational Infrastructure Support Program and The Israeli Ministry of Economy and Industry. Professor Schlaich is supported by a career fellowship from the NHMRC. Associate Professor Marques is supported by a National Heart Foundation Future Leader Fellowship. Professor Head is supported by National Health and Medical Research Council of Australia fellowship.

Author information

Authors and Affiliations

  1. Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Melbourne, VIC, Australia

    Nina Eikelis, John B. Dixon, Elisabeth A. Lambert, Michael T. Fahey & Gavin W. Lambert

  2. Baker Heart & Diabetes Institute, Melbourne, VIC, Australia

    Nina Eikelis, John B. Dixon, Elisabeth A. Lambert, Geoffrey A. Head, Markus P. Schlaich & Gavin W. Lambert

  3. Department of Genetics, University of Cambridge, Cambridge, UK

    Geula Hanin

  4. The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

    Geula Hanin, Yonat Tzur, David S. Greenberg & Hermona Soreq

  5. Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Melbourne, VIC, Australia

    Francine Z. Marques

  6. Department of Pharmacology, Monash University, Melbourne, VIC, Australia

    Geoffrey A. Head

  7. Dobney Hypertension Centre, School of Medicine-Royal Perth Hospital Unit, University of Western Australia, Perth, WA, Australia

    Markus P. Schlaich

Authors
  1. Nina Eikelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John B. Dixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabeth A. Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geula Hanin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yonat Tzur
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David S. Greenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hermona Soreq
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Francine Z. Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael T. Fahey
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Geoffrey A. Head
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Markus P. Schlaich
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gavin W. Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NE, JBD, EAL, MPS, and GWL were involved in all aspects of the study. They conceived and designed the protocol, were involved in participant recruitment and acquisition of data and drafting of the paper. JBD and MPS were involved in clinical aspects of the study, EAL coordinated physiological testing and NE oversaw biochemical and molecular methodologies. FZM provided expert advice around detection of microRNAs, acquired data and drafted and revised the paper. HG, YT, DSG, and HS provided insight into the relationship between microRNA-132 and fatty liver disease, were involved in data acquisition and interpretation and revised the paper. GAH was involved in protocol design, BP data acquisition, and interpretation and revised the paper. MTF was involved in data analysis and interpretation and revised the paper. NE and GWL are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Gavin W. Lambert.

Ethics declarations

Competing interests

There is no competing interests for any of the authors. GL and MPS are investigators in recent studies sponsored by Medtronic. GL has acted as a consultant for Medtronic and has received honoraria or travel support for presentations from Pfizer, Wyeth Pharmaceuticals, Servier, and Medtronic. Professor Schlaich serves on scientific advisory boards for Abbott (formerly Solvay) Pharmaceuticals, BI, Novartis Pharmaceuticals, and Medtronic and has received honoraria and travel support from Abbott, BI, Servier, Novartis, and Medtronic. JBD is a board member of Nestlé Australia and has received payment for consultancy from Apollo Endosurgery, Bariatric Advantage, iNova Pharmaceuticals, and Novo Nordisk. Professor Head has had grant support from Boehringer Ingelheim.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Eikelis, N., Dixon, J.B., Lambert, E.A. et al. MicroRNA-132 may be associated with blood pressure and liver steatosis—preliminary observations in obese individuals. J Hum Hypertens 36, 911–916 (2022). https://doi.org/10.1038/s41371-021-00597-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-021-00597-2

This article is cited by

Search

Advanced search

Quick links