Skip to main content
SpringerLink
Log in

Determination of UCP1 expression in subcutaneous and perirenal adipose tissues of patients with hypertension

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The objective of this study is to determine the property of human perirenal adipose tissue (PAT) and assess the adipose property of PAT in hypertension. Ninety-four patients, including 64 normotensive patients (T-NP) and 30 hypertensive patients (HP), who underwent renal surgery were included. Expression analysis was performed using quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry in PAT and back subcutaneous adipose tissue (bSAT) depots. Compared with bSAT, PAT adipocytes were smaller, and the expressions of uncoupling protein-1 (UCP1) mRNA and protein were markedly higher, while the mRNA expressions of markers for classic beige and white adipocytes were lower in PAT. Immunohistochemistry analysis showed more multilocular UCP1-positive adipocytes in PAT than in bSAT. UCP1 expressions were lower in PAT in HP than in the T-NP or age- and body mass index-matched NP groups. Bigger unilocular adipocytes with less UCP1 staining in PAT were detected in HP than in NP group, although no such difference was observed in bSAT. PAT acts as a brown-like fat. UCP1 expression of PAT was lower in HP than in normotensive patients. UCP1 expression of PAT may serve as a protective indicator for hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. J.M. Friedman, A war on obesity, not the obese. Science 299, 856–858 (2003)

    Article  CAS  PubMed  Google Scholar 

  2. Y. Matsuzawa, T. Funahashi, T. Nakamura, The concept of metabolic syndrome: contribution of visceral fat accumulation and its molecular mechanism. J. Atheroscler. Thromb. 18, 629–639 (2011)

    Article  CAS  PubMed  Google Scholar 

  3. N. Ouchi, J.L. Parker, J.J. Lugus, K. Walsh, Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85–97 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. M.C. Foster, S.J. Hwang, S.A. Porter, J.M. Massaro, U. Hoffmann, C.S. Fox, Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertension 58, 784–790 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. S. Ringholm, J. Grunnet Knudsen, L. Leick, A. Lundgaard, M. Munk Nielsen, H. Pilegaard, PGC-1alpha is required for exercise- and exercise training-induced UCP1 up-regulation in mouse white adipose tissue. PLoS One 8, e64123 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  6. P. Bostrom, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Bostrom, J.H. Choi, J.Z. Long, S. Kajimura, M.C. Zingaretti, B.F. Ving, H. Tu, S. Cinti, K. Hojlund, S.P. Gyqi, B.M. Spiegelman, A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012)

    Article  PubMed Central  PubMed  Google Scholar 

  7. P.A. Svensson, K. Lindberg, J.M. Hoffmann, M. Taube, M.J. Pereira, T. Mohsen-Kanson, A.L. Hafner, M. Rizell, J. Palming, C. Dani, M.K. Svensson, Characterization of brown adipose tissue in the human perirenal depot. Obesity 22, 1830–1837 (2014)

    Article  CAS  PubMed  Google Scholar 

  8. D. Ricquier, Respiration uncoupling and metabolism in the control of energy expenditure. Proc. Nutr. Soc. 64, 47–52 (2005)

    Article  CAS  PubMed  Google Scholar 

  9. L. Chang, L. Villacorta, R. Li, M. Hamblin, W. Xu, C. Dou, J. Zhang, J. Wu, R. Zeng, Y.E. Chen, Loss of perivascular adipose tissue on peroxisome proliferator-activated receptor-gamma deletion in smooth muscle cells impairs intravascular thermoregulation and enhances atherosclerosis. Circulation 126, 1067–1078 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. M. Dong, X. Yang, S. Lim, Z. Cao, J. Honek, H. Lu, C. Zhang, T. Seki, K. Hosaka, E. Wahlberg, J. Yang, L. Zhang, T. Lanne, B. Sun, X. Li, Y. Liu, Y. Zhang, Y. Cao, Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis. Cell Metab. 18, 118–129 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. A.V. Chobanian, G.L. Bakris, H.R. Black, W.C. Cushman, L.A. Green, JLJr Izzo, D.W. Jones, B.J. Materson, S. Oparil, JTJr Wright, E.J. Roccella, The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289, 2560–2572 (2003)

    Article  CAS  PubMed  Google Scholar 

  12. T. Montalcini, G. Gorgone, A. Fava, S. Romeo, C. Gazzaruso, A. Pujia, Carotid and brachial arterial enlargement in postmenopausal women with hypertension. Menopause 19, 145–149 (2012)

    Article  PubMed  Google Scholar 

  13. Z. Wu, P. Puigserver, U. Andersson, C. Zhang, G. Adelmant, V. Mootha, A. Troy, S. Cinti, B. Lowell, R.C. Scarpulla, B.M. Spiegelam, Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115–124 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. P. Seale, B. Bjork, W. Yang, S. Kajimura, S. Chin, S. Kuang, A. Scime, S. Devarakonda, H.M. Conroe, H. Erdjument-Bromage, P. Tempst, M.A. Rudnicki, D.R. Beier, B.M. Spiegelman, PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961–967 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Z. Zhou, S. Yon Toh, Z. Chen, K. Guo, C.P. Ng, S. Ponniah, S.C. Lin, W. Hong, P. Li, Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet. 35, 49–56 (2003)

    Article  PubMed  Google Scholar 

  16. A.M. Cypess, A.P. White, C. Vernochet, T.J. Schulz, R. Xue, C.A. Sass, T.L. Huang, C. Roberts-Toler, L.S. Weiner, C. Sze, A.T. Chacko, L.N. Deschamps, L.M. Herder, N. Truchan, A.L. Glasgow, A.R. Holman, A. Gavrila, P.O. Hasselgren, M.A. Mori, M. Molla, Y.H. Tseng, Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat. Med. 19, 635–639 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. R. Drolet, C. Belanger, M. Fortier, C. Huot, J. Mailloux, D. Legare, A. Tchernof, Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity 17, 424–430 (2009)

    Article  CAS  PubMed  Google Scholar 

  18. O. Osborn, J.M. Olefsky, The cellular and signaling networks linking the immune system and metabolism in disease. Nat. Med. 18, 363–374 (2012)

    Article  CAS  PubMed  Google Scholar 

  19. F. Forner, C. Kumar, C.A. Luber, T. Fromme, M. Klingenspor, M. Mann, Proteome differences between brown and white fat mitochondrial reveal specialized metabolic functions. Cell Metab. 10, 324–335 (2009)

    Article  CAS  PubMed  Google Scholar 

  20. S.J. Yeaman, Hormone-sensitive lipase-new roles for an old enzyme. Biochem. J. 379, 11–22 (2004)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. J. Van de Voorde, B. Pauwels, C. Boydens, K. Decaluwe, Adipocytokines in relation to cardiovascular disease. Metabolism 62, 1513–1521 (2013)

    Article  PubMed  Google Scholar 

  22. K.T. Stepniakowski, T.L. Goodfriend, B.M. Egan, Fatty acids enhance vascular alpha-adrenergic sensitivity. Hypertension 25, 774–778 (1995)

    Article  CAS  PubMed  Google Scholar 

  23. J.E. Hall, A.A. da Silva, J.M. do Carmo, J. Dubinion, S. Hamza, S. Munusamy, G. Smith, D.E. Stec, Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J. Biol. Chem. 285, 17271–17276 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. D. Dicker, E. Atar, R. Kornowski, G.N. Bachar, Increased epicardial adipose tissue thickness as a predictor for hypertension: a cross-sectional observational study. J. Clin. Hypertens. 15, 893–898 (2013)

    Article  CAS  Google Scholar 

  25. J. Wu, P. Bostrom, L.M. Sparks, L. Ye, J.H. Choi, A.H. Giang, M. Khandekar, K.A. Virtanen, P. Nuutila, G. Schaart, K. Huang, H. Tu, W.D. van Marken Lichtenbelt, J. Hoeks, S. Enerback, P. Schrauwen, B.M. Spiegelman, Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. M.E. Lidell, M.J. Betz, O. Dahlqvist Leinhard, M. Heglind, L. Elander, M. Slawik, T. Mussack, D. Nilsson, T. Romu, P. Nuutila, K.A. Virtanen, F. Beuschlein, A. Persson, M. Borga, S. Enerback, Evidence for two types of brown adipose tissue in humans. Nat. Med. 19, 631–634 (2013)

    Article  CAS  PubMed  Google Scholar 

  27. C.S. Tam, V. Lecoultre, E. Ravussin, Brown adipose tissue: mechanisms and potential therapeutic targets. Circulation 125, 2782–2791 (2012)

    Article  PubMed  Google Scholar 

  28. K.I. Stanford, R.J. Middelbeek, K.L. Townsend, D. An, E.B. Nygaard, K.M. Hitchcox, K.R. Markan, K. Nakano, M.F. Hirshman, Y.H. Tseng, L.J. Goodyear, Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J. Clin. Invest. 123, 215–223 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. N. Petrovic, T.B. Walden, I.G. Shabalina, J.A. Timmons, B. Cannon, J. Nedergaard, Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J. Biol. Chem. 285, 7153–7164 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. M. Rosenwald, A. Perdikari, T. Rulicke, C. Wolfrum, Bi-directional interconversion of brite and white adipocytes. Nat. Cell Biol. 15, 659–667 (2013)

    Article  CAS  PubMed  Google Scholar 

  31. A. Gastaldelli, G. Basta, Ectopic fat and cardiovascular disease: what is the link? Nutr. Metab. Cardiovasc. Dis. 20, 481–490 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. F. Ertas, H. Kaya, H. Acet, H. Cil, A. Akyuz, Y. Islamoglu, E. Tekbas, Z. Ariturk, M. Aydin, S. Soydinc, Increased echocardiographic epicardial fat thickness is related to impaired diurnal blood pressure profiles. Blood Press. 21, 202–208 (2012)

    Article  PubMed  Google Scholar 

  33. P. Lee, M.M. Swarbrick, K.K. Ho, Brown adipose tissue in adult humans: a metabolic renaissance. Endocr. Rev. 34, 413–438 (2013)

    Article  CAS  PubMed  Google Scholar 

  34. V. Ouellet, A. Routhier-Labadie, W. Bellemare, L. Lakhal-Chaieb, E. Turcotte, A.C. Carpentier, D. Richard, Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J. Clin. Endocrinol. Metab. 96, 192–199 (2011)

    Article  CAS  PubMed  Google Scholar 

  35. T. Szasz, R.C. Webb, Perivascular adipose tissue: more than just structural support. Clin. Sci. 122, 1–12 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. G. Iacobellis, C. Di Gioia, L. Petramala, C. Chiappetta, V. Serra, L. Zinnamosca, C. Marinelli, A. Ciardi, G. De Toma, C. Letizia, Brown fat expresses adiponectin in humans. Int. J. Endocrinol. 2013, 126751 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  37. C. Letizia, L. Petramala, C.R. Di Gioia, C. Chiappetta, L. Zinnamosca, C. Marinelli, G. Iannucci, A. Ciardi, G. De Toma, G. Iacobellis, Leptin and adiponectin mRNA expression from the adipose tissue surrounding the adrenal neoplasia. J. Clin. Endocrinol. Metab. 100, E101–E104 (2015)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

X Li, J Liu, C Yin, and G Ding conceived and designed the experiments. X Li, J Liu, and G Wang performed the experiments and analyzed data. J Yu, Y Sheng, C Wang, Y Lv, S Lv, H Qi, and W Di contributed reagents/materials/analysis tools. X Li and J Liu wrote the paper. This work was supported by Grants from the National Natural Science Foundation of China (81170796 and 81370950), the Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU (20113012) and also by the Priority Academic Program Development of Jiangsu Higher Education Institutions to Guoxian Ding, and Grants from the National Natural Science Youth Foundation of China (30900504) to Juan Liu.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the research committee of Nanjing Medical University. All participants gave written informed consent before taking part in the study.

Conflict of interest

There are no conflict of interest to declare.

Author information

Author notes

    Authors and Affiliations

    1. Department of Geratology, The First Hospital Affiliated to Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China

      Xueqin Li, Juan Liu, Jing Yu, Yunlu Sheng, Chen Wang, Yifan Lv, Shan Lv, Hanmei Qi, Wenjuan Di & Guoxian Ding

    2. Department of Geratology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, Jiangsu, People’s Republic of China

      Xueqin Li

    3. Departments of Urology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, Jiangsu, People’s Republic of China

      Gongcheng Wang

    4. Department of Urology, The First Hospital Affiliated to Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China

      Changjun Yin

    Authors
    1. Xueqin Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Juan Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Gongcheng Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jing Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Yunlu Sheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Chen Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Yifan Lv
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Shan Lv
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hanmei Qi
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Wenjuan Di
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Changjun Yin
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Guoxian Ding
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Changjun Yin or Guoxian Ding.

    Additional information

    Xueqin Li and Juan Liu have contributed equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOC 24 kb)

    12020_2015_572_MOESM2_ESM.doc

    Supplementary material 2 Other genes expressions in bSAT between HP and T-NP group. (A, B, C, D and E) The expressions of beige adipocyte genes, white adipocyte genes, mitochondrial function genes and adipocyte metabolism-related genes in the samples of bSAT between HP and T-NP group were measured by quantitative RT-PCR (n = 94). (DOC 510 kb)

    12020_2015_572_MOESM3_ESM.doc

    Supplementary material 3 UCP1 and other genes expressions in bSAT between HP and NP group. (A, B, C, D, E and F) The expressions of UCP1 and other BAT genes, beige adipocyte genes, white adipocyte genes, mitochondrial function genes and adipocyte metabolism-related genes in the samples of PAT between the HP and NP groups were measured by quantitative RT-PCR (n = 60). (DOC 630 kb)

    12020_2015_572_MOESM4_ESM.doc

    Supplementary material 4 ADIPOQ and LEP mRNA expressions in PAT between RCC and non-RCC group. The expressions of ADIPOQ and LEP genes in the samples of PAT between RCC and non-RCC group were measured by quantitative RT-PCR (n = 94). (DOC 74 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, X., Liu, J., Wang, G. et al. Determination of UCP1 expression in subcutaneous and perirenal adipose tissues of patients with hypertension. Endocrine 50, 413–423 (2015). https://doi.org/10.1007/s12020-015-0572-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12020-015-0572-3

    Keywords

    Search

    Navigation