Irisin modulates glucose metabolism and inhibits steroidogenesis in bovine granulosa cells

in Reproduction
Authors:
Mathilde DaudonCNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France
Centre de recherche en reproduction et fertilité, Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe QC Canada

Search for other papers by Mathilde Daudon in
Current site
Google Scholar
PubMedClose
https://orcid.org/0000-0001-9998-0421
,
Christelle RaméCNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France

Search for other papers by Christelle Ramé in
Current site
Google Scholar
PubMedClose
,
Christopher PriceCentre de recherche en reproduction et fertilité, Faculté de médecine vétérinaire, Université de Montréal, St-Hyacinthe QC Canada

Search for other papers by Christopher Price in
Current site
Google Scholar
PubMedClose
https://orcid.org/0000-0002-6727-8280
, and
Joëlle DupontCNRS, IFCE, INRAE, Université de Tours, PRC, Nouzilly, France

Search for other papers by Joëlle Dupont in
Current site
Google Scholar
PubMedClose
https://orcid.org/0000-0002-8046-7705
View More View Less

Correspondence should be addressed to J dupont or C Price; Email: joelle.dupont@inrae.fr or christopher.price@umontreal.ca

*(C Price and J Dupont are joint senior authors)

DOI:
https://doi.org/10.1530/REP-22-0404
Volume/Issue:
Volume 165: Issue 5
Page Range:
533–542
Article Type:
Research Article
Online Publication Date:
30 Mar 2023
Copyright:
© Society for Reproduction and Fertility 2023
Restricted access

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $1.00
USD  $1.00

In brief

Fertility in the dairy cow is low during the post-partum period of negative energy balance and high plasma irisin concentrations. This study shows irisin modulates granulosa cell glucose metabolism and impairs steroidogenesis.

Abstract

Fibronectin type III domain-containing 5 (FNDC5) is a transmembrane protein discovered in 2012 that is cleaved to release the adipokine-myokine, irisin. Originally described as an exercise hormone that browns white adipose tissue and increases glucose metabolism, irisin secretion also increases during periods of rapid adipose mobilization, such as the post-partum period in dairy cattle when ovarian activity is suppressed. The effect of irisin on follicle function is unclear and may be species-dependent. In this study, we hypothesized that irisin may compromise granulosa cell function in cattle using a well-established in vitro cell culture model. We detected FNDC5 mRNA and both FNDC5 and cleaved irisin proteins in follicle tissue and in follicular fluid. The abundance of FNDC5 mRNA was increased by the treatment of cells with the adipokine visfatin but not by other adipokines tested. The addition of recombinant irisin to granulosa cells decreased basal and insulin-like growth factor 1- and follicle-stimulating hormone-dependent estradiol and progesterone secretion and increased cell proliferation but had no effect on viability. Irisin decreased GLUT1, GLUT3, and GLUT4 mRNA levels in granulosa cells and increased lactate release in the culture medium. The mechanism of action is in part through MAPK3/1 but not Akt, MAPK14, or PRKAA. We conclude that irisin may regulate bovine folliculogenesis by modulating granulosa cell steroidogenesis and glucose metabolism.

Reproduction is committed to supporting researchers in demonstrating the impact of their articles published in the journal.

The two types of article metrics we measure are (i) more traditional full-text views and pdf downloads, and (ii) Altmetric data, which shows the wider impact of articles in a range of non-traditional sources, such as social media.

More information is on the Reasons to publish page.

Sept 2018 onwards Past Year Past 30 Days
Full Text Views 94 94 32
PDF Downloads 116 116 39

 

  • Collapse
  • Expand
Print ISSN:
1470-1626
Online ISSN:
1741-7899

  • Albrecht E, Schering L, Buck F, Vlach K, Schober H-C, Drevon CA & & Maak S 2020 Irisin: Still chasing shadows. Molecular Metabolism 34 124–135. (https://doi.org/10.1016/j.molmet.2020.01.016)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Basini G, Bussolati S, Iannarelli M, Ragionieri L, Grolli S, Ramoni R, Dodi A, Gazza F & & Grasselli F 2021 The myokine irisin: localization and effects in swine late medium and large antral ovarian follicle. Domestic Animal Endocrinology 74 106576. (https://doi.org/10.1016/j.domaniend.2020.106576)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Baufeld A & & Vanselow J 2022 Lactate-induced effects on bovine granulosa cells are mediated via PKA signaling. Cell and Tissue Research 388 471–477. (https://doi.org/10.1007/s00441-021-03569-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Bonnet M, Bernard L, Bes S & & Leroux C 2013 Selection of reference genes for quantitative real-time PCR normalisation in adipose tissue, muscle, liver and mammary gland from ruminants. Animal 7 1344–1353. (https://doi.org/10.1017/S1751731113000475)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH & Long JZ et al.2012 A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481 463–468. (https://doi.org/10.1038/nature10777)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Burns KH, Owens GE, Fernandez JM, Nilson JH & & Matzuk MM 2002 Characterization of integrin expression in the mouse Ovary1. Biology of Reproduction 67 743–751. (https://doi.org/10.1095/biolreprod.101.000729)

    • Search Google Scholar
    • Export Citation

  • Canépa S, Lainé A-L, Bluteau A & & Fagu C 2008 Validation d’une Méthode Immunoenzymatique pour le Dosage de la Progestérone dans le Plasma des Ovins et des Bovins 12. Available at https://hal.inrae.fr/hal-02667281

    • Search Google Scholar
    • Export Citation

  • Chabrolle C, Tosca L & & Dupont J 2007 Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction 133 719–731. (https://doi.org/10.1530/REP-06-0244)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Chapinal N, Carson ME, LeBlanc SJ, Leslie KE, Godden S, Capel M, Santos JEP, Overton MW & & Duffield TF 2012 The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance. Journal of Dairy Science 95 1301–1309. (https://doi.org/10.3168/jds.2011-4724)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Daudon M, Bigot Y, Dupont J & & Price CA 2022a Irisin and the fibronectin type III domain-containing family: structure, signaling and role in female reproduction. Reproduction 164 R1–R9. (https://doi.org/10.1530/REP-22-0037)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Daudon M, Ramé C, Estienne A, Price C & & Dupont J 2022b Impact of fibronectin type III domain-containing family in the changes in metabolic and hormonal profiles during peripartum period in dairy cows. Frontiers in Veterinary Science 9 960778. (https://doi.org/10.3389/fvets.2022.960778)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Flori L, Testai L & & Calderone V 2021 The “irisin system”: from biological roles to pharmacological and nutraceutical perspectives. Life Sciences 267 118954. (https://doi.org/10.1016/j.lfs.2020.118954)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Fu J, Han Y, Wang J, Liu Y, Zheng S, Zhou L, Jose PA & & Zeng C 2016 Irisin lowers blood pressure by improvement of endothelial dysfunction via AMPK‐Akt‐eNOS‐NO pathway in the spontaneously hypertensive rat. Journal of the American Heart Association 5 e003433. (https://doi.org/10.1161/JAHA.116.003433)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Garten A, Schuster S, Penke M, Gorski T, de Giorgis T & & Kiess W 2015 Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nature Reviews. Endocrinology 11 535–546. (https://doi.org/10.1038/nrendo.2015.117)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Hillier SG, Purohit A & & Reichert LE 1985 Control of granulosa cell lactate production by follicle-stimulating hormone and androgen. Endocrinology 116 1163–1167. (https://doi.org/10.1210/endo-116-3-1163)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Huh JY, Mougios V, Kabasakalis A, Fatouros I, Siopi A, Douroudos II, Filippaios A, Panagiotou G, Park KH & & Mantzoros CS 2014 Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. Journal of Clinical Endocrinology and Metabolism 99 E2154–E2161. (https://doi.org/10.1210/jc.2014-1437)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Jungheim ES, Macones GA, Odem RR, Patterson BW, Lanzendorf SE, Ratts VS & & Moley KH 2011 Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertility and Sterility 95 1970–1974. (https://doi.org/10.1016/j.fertnstert.2011.01.154)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Kim H, Wrann CD, Jedrychowski M, Vidoni S, Kitase Y, Nagano K, Zhou C, Chou J, Parkman V-JA & Novick SJ et al.2018 Irisin mediates effects on bone and fat via αV integrin receptors. Cell 175 1756–1768.e17. (https://doi.org/10.1016/j.cell.2018.10.025)

    • Search Google Scholar
    • Export Citation

  • Li X, Fang W, Hu Y, Wang Y & & Li J 2015 Characterization of fibronectin type III domain-containing protein 5 (FNDC5) gene in chickens: cloning, tissue expression, and regulation of its expression in the muscle by fasting and cold exposure. Gene 570 221–229. (https://doi.org/10.1016/j.gene.2015.06.022)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Lombardi AM, Fabris R, Bassetto F, Serra R, Leturque A, Federspil G, Girard J & & Vettor R 1999 Hyperlactatemia reduces muscle glucose uptake and GLUT-4 mRNA while increasing (E1α)PDH gene expression in rat. American Journal of Physiology 276 E922–E929. (https://doi.org/10.1152/ajpendo.1999.276.5.E922)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Luo Y, Qiao X, Ma Y, Deng H, Xu CC & & Xu L 2021 Irisin deletion induces a decrease in growth and fertility in mice. Reproductive Biology and Endocrinology 19 22. (https://doi.org/10.1186/s12958-021-00702-7)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Maillard V, Uzbekova S, Guignot F, Perreau C, Ramé C, Coyral-Castel S & & Dupont J 2010 Effect of adiponectin on bovine granulosa cell steroidogenesis, oocyte maturation and embryo development. Reproductive Biology and Endocrinology: RB&E 8 23. (https://doi.org/10.1186/1477-7827-8-23)

    • Search Google Scholar
    • Export Citation

  • McArt JAA, Nydam DV, Oetzel GR, Overton TR & & Ospina PA 2013 Elevated non-esterified fatty acids and β-hydroxybutyrate and their association with transition dairy cow performance. Veterinary Journal 198 560–570. (https://doi.org/10.1016/j.tvjl.2013.08.011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Mellouk N, Rame C, Touzé JL, Briant E, Ma L, Guillaume D, Lomet D, Caraty A, Ntallaris T & Humblot P et al.2017 Involvement of plasma adipokines in metabolic and reproductive parameters in Holstein dairy cows fed with diets with differing energy levels. Journal of Dairy Science 100 8518–8533. (https://doi.org/10.3168/jds.2017-12657)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Nie Y & & Liu D 2017 N-Glycosylation is required for FDNC5 stabilization and irisin secretion. Biochemical Journal 474 3167–3177. (https://doi.org/10.1042/BCJ20170241)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Opsomer G 2015 Interaction between metabolic challenges and productivity in high yielding dairy cows. Japanese Journal of Veterinary Research 63(Supplement 1) S1–S14. (https://doi.org/10.14943/jjvr.63.suppl.s1)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Ospina PA, McArt JA, Overton TR, Stokol T & & Nydam DV 2013 Using nonesterified fatty acids and β-hydroxybutyrate concentrations during the transition period for herd-level monitoring of increased risk of disease and decreased reproductive and milking performance. Veterinary Clinics of North America: Food Animal Practice 29 387–412. (https://doi.org/10.1016/j.cvfa.2013.04.003)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Persson JL, Zhang Q, Wang XY, Ravnik SE, Muhlrad S & & Wolgemuth DJ 2005 Distinct roles for the mammalian A-type cyclins during oogenesis. Reproduction 130 411–422. (https://doi.org/10.1530/rep.1.00719)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Poretsky L, Islam J, Avtanski D, Lin YK, Shen YL, Hirth Y, Lesser M, Rosenwaks Z & & Seto-Young D 2017 Reproductive effects of irisin: initial in vitro studies. Reproductive Biology 17 285–288. (https://doi.org/10.1016/j.repbio.2017.05.011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rabiee F, Lachinani L, Ghaedi S, Nasr-Esfahani MH, Megraw TL & & Ghaedi K 2020 New insights into the cellular activities of Fndc5/Irisin and its signaling pathways. Cell and Bioscience 10 51. (https://doi.org/10.1186/s13578-020-00413-3)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Reverchon M, Bertoldo MJ, Ramé C, Froment P & & Dupont J 2014a Chemerin (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks oocyte meiotic progression in bovine Species1. Biology of Reproduction 90. (https://doi.org/10.1095/biolreprod.113.117044)

    • Search Google Scholar
    • Export Citation

  • Reverchon M, Ramé C, Cognié J, Briant E, Elis S, Guillaume D & & Dupont J 2014b Resistin in Dairy Cows: Plasma Concentrations during Early Lactation, Expression and Potential Role in Adipose Tissue ed S V Pizzo. PLoS One 9 e93198. (https://doi.org/10.1371/journal.pone.0093198)

    • Search Google Scholar
    • Export Citation

  • Reverchon M, Rame C, Bunel A, Chen W, Froment P & & Dupont J 2016 Visfatin (NAMPT) improves in vitro IGF1-induced steroidogenesis and IGF1 receptor signaling through SIRT1 in Bovine Granulosa Cells. In Biology of Reproduction 94 54. (https://doi.org/10.1095/biolreprod.115.134650)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Rodríguez A, Becerril S, Méndez-Giménez L, Ramírez B, Sáinz N, Catalán V, Gómez-Ambrosi J & & Frühbeck G 2015 Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice. International Journal of Obesity 39 397–407. (https://doi.org/10.1038/ijo.2014.166)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Santos JEP, Bisinotto RS & & Ribeiro ES 2016 Mechanisms underlying reduced fertility in anovular dairy cows. Theriogenology 86 254–262. (https://doi.org/10.1016/j.theriogenology.2016.04.038)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Sharma A, Baddela VS, Becker F, Dannenberger D, Viergutz T & & Vanselow J 2019 Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance. Endocrine Connections 8 493–505. (https://doi.org/10.1530/EC-19-0011)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Spicer LJ, Schreiber NB, Lagaly DV, Aad PY, Douthit LB & & Grado-Ahuir JA 2011 Effect of resistin on granulosa and theca cell function in cattle. Animal Reproduction Science 124 19–27. (https://doi.org/10.1016/j.anireprosci.2011.01.005)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Tosca L, Chabrolle C, Uzbekova S & & Dupont J 2007a Effects of metformin on bovine granulosa cells steroidogenesis: possible involvement of adenosine 5′ monophosphate-activated protein kinase (AMPK)1. Biology of Reproduction 76 368–378. (https://doi.org/10.1095/biolreprod.106.055749)

    • Search Google Scholar
    • Export Citation

  • Tosca L, Uzbekova S, Chabrolle C & & Dupont J 2007b Possible role of 5′AMP-activated protein kinase in the metformin-mediated arrest of bovine oocytes at the germinal vesicle stage during in vitro Maturation1. Biology of Reproduction 77 452–465. (https://doi.org/10.1095/biolreprod.107.060848)

    • Search Google Scholar
    • Export Citation

  • Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A & & Speleman F 2002 Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biology 3 RESEARCH0034. (https://doi.org/10.1186/gb-2002-3-7-research0034)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Vaughan RA, Gannon NP, Barberena MA, Garcia-Smith R, Bisoffi M, Mermier CM, Conn CA & & Trujillo KA 2014 Characterization of the metabolic effects of irisin on skeletal muscle in vitro. Diabetes, Obesity and Metabolism 16 711–718. (https://doi.org/10.1111/dom.12268)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zachow RJ & & Magoffin DA 1997 Direct intraovarian effects of leptin: impairment of the synergistic action of insulin-like growth factor-I on follicle-stimulating hormone-dependent Estradiol-17β production by rat ovarian granulosa cells*. Endocrinology 138 847–850. (https://doi.org/10.1210/endo.138.2.5035)

    • PubMed
    • Search Google Scholar
    • Export Citation

  • Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y, Qi L, Zhang M, Wang X & Cui T et al.2014 Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 63 514–525. (https://doi.org/10.2337/db13-1106)

    • PubMed
    • Search Google Scholar
    • Export Citation