Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi

4 Issues per year


CiteScore 2017: 2.48

SCImago Journal Rank (SJR) 2017: 1.021
Source Normalized Impact per Paper (SNIP) 2017: 0.830

Online
ISSN
1868-1891
See all formats and pricing
More options …
Volume 33, Issue 2

Issues

White and beige adipocytes: are they metabolically distinct?

Diane M. Sepa-Kishi
  • Muscle Health Research Center, School of Kinesiology and Health Science, York University, Toronto, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rolando B. Ceddia
  • Corresponding author
  • Muscle Health Research Centre, School of Kinesiology and Health Science, York University, 4700 Keele St., North York, Ontario, M3J 13P, Canada, Phone: 416-736-2100 (Ext. 77204), Fax: 416-736-5774
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-21 | DOI: https://doi.org/10.1515/hmbci-2018-0003

Abstract

The white adipose tissue (WAT) exhibits great plasticity and can undergo “browning” and acquire features of the brown adipose tissue (BAT), which takes place following cold exposure, chronic endurance exercise or β3-adrenergic stimulation. WAT that underwent browning is characterized by the presence of “beige” adipocytes, which are morphologically similar to brown adipocytes, express uncoupling protein 1 (UCP1) and are considered thermogenically competent. Thus, inducing a BAT-like phenotype in the WAT could promote energy dissipation within this depot, reducing the availability of substrate that would otherwise be stored in the WAT. Importantly, BAT in humans only represents a small proportion of total body mass, which limits the thermogenic capacity of this tissue. Therefore, browning of the WAT could significantly expand the energy-dissipating capacity of the organism and be of therapeutic value in the treatment of metabolic diseases. However, the question remains as to whether WAT indeed changes its metabolic profile from an essentially fat storage/release compartment to an energy dissipating compartment that functions much like BAT. Here, we discuss the differences with respect to thermogenic capacity and metabolic characteristics between white and beige adipocytes to determine whether the latter cells indeed significantly enhance their capacity to dissipate energy through UCP1-mediated mitochondrial uncoupling or by the activation of alternative UCP1-independent futile cycles.

Keywords: adipose tissue plasticity; beige adipocytes; brown adipose tissue; energy dissipation; fat oxidation; futile cycles; lipolysis; thermogenesis; UCP1; white adipose tissue

References

  • [1]

    Choi CH, Cohen P. Adipose crosstalk with other cell types in health and disease. Exp Cell Res. 2017;360:6–11.PubMedCrossrefGoogle Scholar

  • [2]

    Trayhurn P. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand. 2005;184:285–93.PubMedCrossrefGoogle Scholar

  • [3]

    Cuthbertson DJ, Steele T, Wilding JP, Halford JC, Harrold JA, Hamer M, et al. What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications? Int J Obes. 2017;41:853–65.CrossrefGoogle Scholar

  • [4]

    Merlotti C, Ceriani V, Morabito A, Pontiroli AE. Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis. Int J Obes. 2017;41:672–82.CrossrefGoogle Scholar

  • [5]

    Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21:697–738.PubMedCrossrefGoogle Scholar

  • [6]

    Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Pénicaud L, et al. Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci. 1992;103:931–42.PubMedGoogle Scholar

  • [7]

    Cousin B, Casteilla L, Dani C, Muzzin P, Revelli JP, Penicaud L. Adipose tissues from various anatomical sites are characterized by different patterns of gene expression and regulation. Biochem J. 1993;292:873–6.PubMedCrossrefGoogle Scholar

  • [8]

    Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab. 2010;298:E1244–53.CrossrefGoogle Scholar

  • [9]

    Wu MV, Bikopoulos G, Ceddia RB, Wu MV, Bikopoulos G, Hung S, et al. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. J Biol Chem. 2014;289:34129–40.CrossrefGoogle Scholar

  • [10]

    De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, et al. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis. 2013;23:582–90.CrossrefPubMedGoogle Scholar

  • [11]

    Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.PubMedCrossrefGoogle Scholar

  • [12]

    Sepa-Kishi DM, Ceddia RB. Exercise-mediated effects on white and brown adipose tissue plasticity and metabolism. Exerc Sport Sci Rev. 2016;44:37–44.CrossrefGoogle Scholar

  • [13]

    Park JW, Jung K-H, Lee JH, Quach CH, Moon S-H, Cho YS, et al. 18F-FDG PET/CT monitoring of beta3 agonist-stimulated brown adipocyte recruitment in white adipose tissue. J Nucl Med. 2015;56:153–8.PubMedCrossrefGoogle Scholar

  • [14]

    Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.CrossrefPubMedGoogle Scholar

  • [15]

    Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, et al. Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci USA. 2017;114:8649–54.CrossrefGoogle Scholar

  • [16]

    Fruhbeck G. Overview of adipose tissue and its role in obesity and metabolic disorders. In: Yang K, editor. Adipose tissue protocols. 2nd ed. London, ON: Humana Press Inc.; 2008. p. 1–22.Google Scholar

  • [17]

    Lee M-J, Wu Y, Fried SK. Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med. 2013;34:1–11.PubMedCrossrefGoogle Scholar

  • [18]

    Cinti S. Transdifferentiation properties of adipocytes in the adipose organ. Am J Physiol Endocrinol Metab. 2009;297:E977–86.CrossrefPubMedGoogle Scholar

  • [19]

    Barneda D, Frontini A, Cinti S, Christian M. Dynamic changes in lipid droplet-associated proteins in the “browning” of white adipose tissues. Biochim Biophys Acta. 2013;1831:924–33.CrossrefPubMedGoogle Scholar

  • [20]

    Shabalina I, Petrovic N, DeJong JA, Kalinovich A, Cannon B, Nedergaard J. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 2013;5:1196–203.PubMedCrossrefGoogle Scholar

  • [21]

    Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, et al. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest. 2011;121:96–105.CrossrefPubMedGoogle Scholar

  • [22]

    Sanchez-Gurmaches J, Guertin DA. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun. 2014;19:4099.Google Scholar

  • [23]

    Himms-Hagen J, Melnyk A, Zingaretti MC, Ceresi E, Barbatelli G, Cinti S. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol. 2000;279:C670–81.CrossrefPubMedGoogle Scholar

  • [24]

    Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor y (PPARy) 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. 2010;285:7153–64.CrossrefGoogle Scholar

  • [25]

    Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A-H, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150:366–76.PubMedCrossrefGoogle Scholar

  • [26]

    Tseng Y-H, Kokkotou E, Schulz TJ, Huang TL, Winnay J, Taniguchi CM, et al. New role of bone morphogenic protein 7 in brown adipogenesis and energy expenditure. Nature. 2008;454:1000–6.CrossrefGoogle Scholar

  • [27]

    Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, et al. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev. 2008;22:1397–409.CrossrefGoogle Scholar

  • [28]

    Iida S, Chen W, Nakadai T, Ohkuma Y, Roeder RG. PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1. Genes Dev. 2015;29:308–21.CrossrefPubMedGoogle Scholar

  • [29]

    Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab. 2007;6:38–54.CrossrefPubMedGoogle Scholar

  • [30]

    Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, et al. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell. 2014;156:304–16.CrossrefGoogle Scholar

  • [31]

    Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med. 2013;19:1338–44.CrossrefPubMedGoogle Scholar

  • [32]

    Frontini A, Vitali A, Perugini J, Murano I, Romiti C, Ricquier D, et al. White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma. Biochim Biophys Acta. 2013;1831:950–9.CrossrefPubMedGoogle Scholar

  • [33]

    DiGirolamo M. Measurements of glucose conversion to its metabolites. In: Ailhaud G, editor. Methods in molecular biology adipose tissue protocols. Totowa, NJ: Humana Press Inc.; 2001. p. 181–92.Google Scholar

  • [34]

    Flatt JP, Ball EG. Studies on the metabolism of adipose tissue : XV. An evaluation of the major pathways of glucose catabolism as influenced by insulin and epinephrine. J Biol Chem. 1964;239:675–85.Google Scholar

  • [35]

    Frayn KN, Langin D, Karpe F. Fatty acid-induced mitochondrial uncoupling in adipocytes is not a promising target for treatment of insulin resistance unless adipocyte oxidative capacity is increased. Diabetologia. 2008;51:394–7.CrossrefGoogle Scholar

  • [36]

    Martin BR, Denton RM. The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. Biochem J. 1970;117:861–77.CrossrefPubMedGoogle Scholar

  • [37]

    Goetzman ES. The regulation of acyl-CoA dehydrogenases in adipose tissue by rosiglitazone. Obesity. 2009;17:196–8.CrossrefGoogle Scholar

  • [38]

    Forner F, Kumar C, Luber CA, Fromme T, Klingenspor M, Mann M. Proteome differences between brown and white fat mitochondria reveal specialized metabolic functions. Cell Metab. 2009;10:324–35.CrossrefGoogle Scholar

  • [39]

    Margolis S, Vaughan M. Alpha-glycerophosphate synthesis and breakdown in homogenates of adipose tissue. J Biol Chem. 1962;237:44–8.PubMedGoogle Scholar

  • [40]

    Vaughan M. The production and release of glycerol by adipose tissue incubated in vitro. J Biol Chem. 1962;237:3354–8.PubMedGoogle Scholar

  • [41]

    Edens NK, Leibel RL, Hirsch J. Mechanism of free fatty acid re-esterification in human adipocytes in vitro. J Lipid Res. 1990;31:1423–31.PubMedGoogle Scholar

  • [42]

    Reshef L, Hanson RW, Ballard FJ. A possible physiological role for glyceroneogenesis in rat adipose tissue. J Biol Chem. 1970;245:5979–84.PubMedGoogle Scholar

  • [43]

    Brooks B, Arch JR, Newsholme EA. Effects of hormones on the rate of the triacylglycerol/fatty acid substrate cycle in adipocytes and epididymal fat pads. FEBS Lett. 1982;146:327–30.PubMedCrossrefGoogle Scholar

  • [44]

    Nye C, Kim J, Kalhan SC, Hanson RW. Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol Metab. 2008;19:356–61.CrossrefPubMedGoogle Scholar

  • [45]

    Baldwin RL. Metabolic functions affecting the contribution of adipose tissue to total energy expenditure. Fed Proc. 1970;29:1277–83.PubMedGoogle Scholar

  • [46]

    Gauthier M-S, Miyoshi H, Souza SC, Cacicedo JM, Saha AK, Greenberg AS, et al. AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte. J Biol Chem. 2008;283:16514–24.PubMedCrossrefGoogle Scholar

  • [47]

    Rognstad R, Katz J. The balance of pyridine nucleotides and ATP in adipose tissue. Proc Natl Acad Sci USA. 1966;55:1148–56.CrossrefGoogle Scholar

  • [48]

    Flachs P, Rossmeisl M, Kuda O, Kopecky J. Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: a key to lean phenotype. Biochim Biophys Acta. 2013;1831:986–1003.CrossrefPubMedGoogle Scholar

  • [49]

    Keipert S, Jastroch M. Brite/beige fat and UCP1 – is it thermogenesis? Biochim Biophys Acta. 2014;1837:1075–82.PubMedCrossrefGoogle Scholar

  • [50]

    Nedergaard J, Cannon B. UCP1 mRNA does not produce heat. Biochim Biophys Acta. 2013;1831:943–9.CrossrefPubMedGoogle Scholar

  • [51]

    Li Y, Fromme T, Schweizer S, Schöttl T, Klingenspor M. Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. EMBO Rep. 2014;15:1069–76.CrossrefGoogle Scholar

  • [52]

    Bartesaghi S, Hallen S, Huang L, Svensson P-A, Momo RA, Wallin S, et al. Thermogenic activity of UCP1 in human white fat-derived beige adipocytes. Mol Endocrinol. 2014;29:130–9.Google Scholar

  • [53]

    Ikeda K, Kang Q, Yoneshiro T, Camporez JP, Maki H, Homma M, et al. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat Med. 2017;23:1454–65.PubMedCrossrefGoogle Scholar

  • [54]

    Schöttl T, Kappler L, Braun K, Fromme T, Klingenspor M. Limited mitochondrial capacity of visceral versus subcutaneous white adipocytes in male C57BL/6N mice. Endocrinology. 2015;156:923–33.PubMedCrossrefGoogle Scholar

  • [55]

    Pistor KE, Sepa-Kishi DM, Hung S, Ceddia RB. Lipolysis, lipogenesis, and adiposity are reduced while fatty acid oxidation is increased in visceral and subcutaneous adipocytes of endurance-trained rats. Adipocyte. 2014;4:22–31.PubMedGoogle Scholar

  • [56]

    Gaidhu MP, Frontini A, Hung S, Pistor K, Cinti S, Ceddia RB. Chronic AMP-kinase activation with AICAR reduces adiposity by remodeling adipocyte metabolism and increasing leptin sensitivity. J Lipid Res. 2011;52:1702–11.PubMedCrossrefGoogle Scholar

  • [57]

    Gaidhu MP, Fediuc S, Anthony NM, So M, Mirpourian M, Perry RL, et al. Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. J Lipid Res. 2009;50:704–15.PubMedCrossrefGoogle Scholar

  • [58]

    Kopecký J, Rossmeisl M, Flachs P, Bardová K, Brauner P. Mitochondrial uncoupling and lipid metabolism in adipocytes. Biochem Soc Trans. 2001;29:791–7.PubMedCrossrefGoogle Scholar

  • [59]

    Kopecky J, Clarke G, Enerbäck S, Spiegelman B, Kozak LP. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest. 1995;96:2914–23.CrossrefPubMedGoogle Scholar

  • [60]

    Si Y, Palani S, Jayaraman A, Lee K. Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism. J Lipid Res. 2007;48:826–36.PubMedCrossrefGoogle Scholar

  • [61]

    Rossmeisl M, Syrový I, Baumruk F, Flachs P, Janovská P, Kopecký J. Decreased fatty acid synthesis due to mitochondrial uncoupling in adipose tissue. FASEB J. 2000;14:1793–800.CrossrefPubMedGoogle Scholar

  • [62]

    Wang T, Zang Y, Ling W, Corkey BE, Guo W. Metabolic partitioning of endogenous fatty acid in adipocytes. Obes Res. 2003;11:880–7.CrossrefPubMedGoogle Scholar

  • [63]

    Ukropec J, Anunciado RP, Ravussin Y, Hulver MW, Kozak LP. UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice. J Biol Chem. 2006;281:31894–908.CrossrefGoogle Scholar

  • [64]

    Sepa-Kishi DM, Sotoudeh-Nia Y, Iqbal A, Bikopoulos G, Ceddia RB. Cold acclimation causes fiber type-specific responses in glucose and fat metabolism in rat skeletal muscles. Sci Rep. 2017;7:15430.PubMedCrossrefGoogle Scholar

  • [65]

    Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA, et al. Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med. 2012;18:1575–9.PubMedCrossrefGoogle Scholar

  • [66]

    Simcox J, Geoghegan G, Maschek JA, Bensard CL, Pasquali M, Miao R, et al. Global analysis of plasma lipids identifies liver-derived acylcarnitines as a fuel source for brown fat thermogenesis. Cell Metab. 2017;26:509–22.e6.CrossrefPubMedGoogle Scholar

  • [67]

    Nyman E, Bartesaghi S, Melin Rydfalk R, Eng S, Pollard C, Gennemark P, et al. Systems biology reveals uncoupling beyond UCP1 in human white fat-derived beige adipocytes. NPJ Syst Biol Appl. 2017;3:29.CrossrefPubMedGoogle Scholar

  • [68]

    Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, et al. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell. 2015;163:643–55.CrossrefPubMedGoogle Scholar

  • [69]

    Bertholet AM, Kazak L, Chouchani ET, Bogaczyńska MG, Paranjpe I, Wainwright GL, et al. Mitochondrial patch clamp of beige adipocytes reveals UCP1-positive and UCP1-negative cells both exhibiting futile creatine cycling. Cell Metab. 2017;25:811–22.e4.CrossrefPubMedGoogle Scholar

  • [70]

    Kazak L, Chouchani ET, Lu GZ, Jedrychowski MP, Bare CJ, Mina AI, et al. Genetic depletion of adipocyte creatine metabolism inhibits diet-induced thermogenesis and drives obesity. Cell Metab. 2017;26:693.CrossrefPubMedGoogle Scholar

  • [71]

    Zhang Y, Liu Q, Yu J, Yu S, Wang J, Qiang L, et al. Locally induced adipose tissue browning by microneedle patch for obesity treatment. ACS Nano. 2017;11:9223–30.CrossrefPubMedGoogle Scholar

About the article

Received: 2018-01-08

Accepted: 2018-01-22

Published Online: 2018-02-21


Funding Source: Natural Sciences and Engineering Research Council of Canada

Award identifier / Grant number: RGPIN 2016-05358

Funding Source: Canada Foundation for Innovation

Funding Source: Ontario Research Foundation

Award identifier / Grant number: RBC

This research was funded by a Discovery Grant from the Natural Science and Engineering Research Council of Canada (NSERC) (RGPIN 2016-05358) and by infrastructure grants from the Canada Foundation for Innovation (CFI) and the Ontario Research Fund (ORF) awarded to RBC. DMSK was supported by the Elia Scholarship and the NSERC Alexander Graham Bell Canada Graduate Doctoral Scholarship.


Author Statement

Conflict of interest: The authors declare no conflict of interest.

Informed consent: Informed consent is not applicable.

Ethical approval: The conducted research is not related to either human or animals use.


Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 33, Issue 2, 20180003, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2018-0003.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
André C. Carpentier, Denis P. Blondin, Kirsi A. Virtanen, Denis Richard, François Haman, and Éric E. Turcotte
Frontiers in Endocrinology, 2018, Volume 9

Comments (0)

Please log in or register to comment.
Log in