Effects of Adipocyte-derived Factors on the Adrenal Cortex

Author(s): Hiroki Shimada, Erika Noro, Susumu Suzuki, Jun Sakamoto, Ikuko Sato, Rehana Parvin, Atsushi Yokoyama, Akira Sugawara*.

Journal Name: Current Molecular Pharmacology

Volume 13 , Issue 1 , 2020

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Abstract:

Background and Objective: Obesity is highly complicated by hypertension and hyperglycemia. In particular, it has been proposed that obesity-related hypertension is caused by adipocyte-derived factors that are recognized as undetermined proteins secreted from adipocytes. Adipocyte-derived factors have been known to be related to aldosterone secretion in the adrenal gland. So far, Wnt proteins, CTRP-1, VLDL, LDL, HDL and leptin have been demonstrated to stimulate aldosterone secretion. In contrast, it has not yet been clarified whether adipocyte-derived factors also affect adrenal cortisol secretion.

Methods and Results: In the present study, we investigated the effect of adipocyte-derived factors on cortisol synthase gene CYP11B1 mRNA expression in vitro study using adrenocortical carcinoma H295R cells and mouse fibroblast 3T3-L1cells. Interestingly, adipocyte-derived factors were demonstrated to have the ability to stimulate CYP11B1 mRNA expression.

Conclusion: Since CYP11B1 is well known as a limiting enzyme of cortisol synthesis, our study suggests that adipocyte-derived factors may stimulate cortisol secretion, as well as aldosterone secretion. Taken together, adipocyte-derived factors may be the cause of metabolic syndrome due to their stimulating effects on aldosterone/cortisol secretion. Therefore, the innovation of novel drugs against them may possibly be a new approach against metabolic syndrome.

Keywords: Obesity, adipocyte, adrenal, CYP11B1, CYP11B2, cortisol.

[1]
Ehrhart-Bornstein, M.; Lamounier-Zepter, V.; Schraven, A.; Langenbach, J.; Willenberg, H.S.; Barthel, A.; Hauner, H.; McCann, S.M.; Scherbaum, W.A.; Bornstein, S.R. Human adipocytes secrete mineralocorticoid-releasing factors. Proc. Natl. Acad. Sci. USA, 2003, 100(24), 14211-14216.
[http://dx.doi.org/10.1073/pnas.2336140100] [PMID: 14614137]
[2]
Nagase, M.; Yoshida, S.; Shibata, S.; Nagase, T.; Gotoda, T.; Ando, K.; Fujita, T. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J. Am. Soc. Nephrol., 2006, 17(12), 3438-3446.
[http://dx.doi.org/10.1681/ASN.2006080944] [PMID: 17082236]
[3]
Schinner, S.; Willenberg, H.S.; Krause, D.; Schott, M.; Lamounier-Zepter, V.; Krug, A.W.; Ehrhart-Bornstein, M.; Bornstein, S.R.; Scherbaum, W.A. Adipocyte-derived products induce the transcription of the StAR promoter and stimulate aldosterone and cortisol secretion from adrenocortical cells through the Wnt-signaling pathway. Int. J. Obes., 2007, 31(5), 864-870.
[http://dx.doi.org/10.1038/sj.ijo.0803508] [PMID: 17211444]
[4]
Jeon, J.H.; Kim, K.Y.; Kim, J.H.; Baek, A.; Cho, H.; Lee, Y.H.; Kim, J.W.; Kim, D.; Han, S.H.; Lim, J-S.; Kim, K.I.; Yoon, D.Y.; Kim, S-H.; Oh, G.T.; Kim, E.; Yang, Y. A novel adipokine CTRP1 stimulates aldosterone production. FASEB J., 2008, 22(5), 1502-1511.
[http://dx.doi.org/10.1096/fj.07-9412com] [PMID: 18171693]
[5]
Xing, Y.; Rainey, W.E.; Apolzan, J.W.; Francone, O.L.; Harris, R.B.S.; Bollag, W.B. Adrenal cell aldosterone production is stimulated by very-low-density lipoprotein (VLDL). Endocrinology, 2012, 153(2), 721-731.
[http://dx.doi.org/10.1210/en.2011-1752] [PMID: 22186415]
[6]
Xing, Y.; Cohen, A.; Rothblat, G.; Sankaranarayanan, S.; Weibel, G.; Royer, L.; Francone, O.L.; Rainey, W.E. Aldosterone production in human adrenocortical cells is stimulated by high-density lipoprotein 2 (HDL2) through increased expression of aldosterone synthase (CYP11B2). Endocrinology, 2011, 152(3), 751-763.
[http://dx.doi.org/10.1210/en.2010-1049] [PMID: 21239432]
[7]
Huby, A-C.C.; Antonova, G.; Groenendyk, J.; Gomez-Sanchez, C.E.; Bollag, W.B.; Filosa, J.A.; Belin de Chantemèle, E.J.; De Chantemèle, E.J.B. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation, 2015, 132(22), 2134-2145.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018226] [PMID: 26362633]
[8]
Willert, K.; Nusse, R. Wnt proteins. Cold Spring Harb. Perspect. Biol., 2012, 4(9) a007864
[http://dx.doi.org/10.1101/cshperspect.a007864] [PMID: 22952392]
[9]
Nusse, R.; Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1), 99-109.
[http://dx.doi.org/10.1016/0092-8674(82)90409-3] [PMID: 6297757]
[10]
Wood, M.A.; Acharya, A.; Finco, I.; Swonger, J.M.; Elston, M.J.; Tallquist, M.D.; Hammer, G.D. Fetal adrenal capsular cells serve as progenitor cells for steroidogenic and stromal adrenocortical cell lineages in M. musculus. Development, 2013, 140(22), 4522-4532.
[http://dx.doi.org/10.1242/dev.092775] [PMID: 24131628]
[11]
King, P.; Paul, A.; Laufer, E. Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages. Proc. Natl. Acad. Sci. USA, 2009, 106(50), 21185-21190.
[http://dx.doi.org/10.1073/pnas.0909471106] [PMID: 19955443]
[12]
Drelon, C.; Berthon, A.; Sahut-Barnola, I.; Mathieu, M.; Dumontet, T.; Rodriguez, S.; Batisse-Lignier, M.; Tabbal, H.; Tauveron, I.; Lefrançois-Martinez, A.M.; Pointud, J.C.; Gomez-Sanchez, C.E.; Vainio, S.; Shan, J.; Sacco, S.; Schedl, A.; Stratakis, C.A.; Martinez, A.; Val, P. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development. Nat. Commun., 2016, 7, 12751.
[http://dx.doi.org/10.1038/ncomms12751] [PMID: 27624192]
[13]
Gaujoux, S.; Hantel, C.; Launay, P.; Bonnet, S.; Perlemoine, K.; Lefèvre, L.; Guillaud-Bataille, M.; Beuschlein, F.; Tissier, F.; Bertherat, J.; Rizk-Rabin, M.; Ragazzon, B. Silencing mutated β-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R. PLoS One, 2013, 8(2) e55743
[http://dx.doi.org/10.1371/journal.pone.0055743] [PMID: 23409032]
[14]
Schäffler, A.; Buechler, C. CTRP family: linking immunity to metabolism. Trends Endocrinol. Metab., 2012, 23(4), 194-204.
[http://dx.doi.org/10.1016/j.tem.2011.12.003] [PMID: 22261190]
[15]
Wang, H.; Wang, R.; Du, D.; Li, F.; Li, Y. Serum levels of C1q/TNF-related protein-1 (CTRP-1) are closely associated with coronary artery disease. BMC Cardiovasc. Disord., 2016, 16, 92.
[http://dx.doi.org/10.1186/s12872-016-0266-7] [PMID: 27169633]
[16]
Li, Y.; Ozment, T.; Wright, G.L.; Peterson, J.M. Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology. PLoS One, 2016, 11(10)e0164593
[http://dx.doi.org/10.1371/journal.pone.0164593] [PMID: 27727322]
[17]
Saha, S.; Willenberg, H.S.; Bornstein, S.R.; Graessler, J.; Kopprasch, S. Diabetic lipoproteins and adrenal aldosterone synthesis--a possible pathophysiological link? Horm. Metab. Res., 2012, 44(3), 239-244.
[http://dx.doi.org/10.1055/s-0031-1295459] [PMID: 22147656]
[18]
Capponi, A.M. Regulation of cholesterol supply for mineralocorticoid biosynthesis. Trends Endocrinol. Metab., 2002, 13(3), 118-121.
[http://dx.doi.org/10.1016/S1043-2760(01)00538-0] [PMID: 11893525]
[19]
Huby, A.C.; Otvos, L., Jr; Belin de Chantemèle, E.J. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertension, 2016, 67(5), 1020-1028.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06642] [PMID: 26953321]
[20]
Hofmann, A.; Peitzsch, M.; Brunssen, C.; Mittag, J.; Jannasch, A.; Frenzel, A.; Brown, N.; Weldon, S.M.; Eisenhofer, G.; Bornstein, S.R.; Morawietz, H. Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes. Horm. Metab. Res., 2017, 49(1), 43-49.
[PMID: 27813053]
[21]
Bornstein, S.R.; Uhlmann, K.; Haidan, A.; Ehrhart-Bornstein, M.; Scherbaum, W.A. Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly. Diabetes, 1997, 46(7), 1235-1238.
[http://dx.doi.org/10.2337/diab.46.7.1235] [PMID: 9200662]
[22]
Walczak, E.M.; Kuick, R.; Finco, I.; Bohin, N.; Hrycaj, S.M.; Wellik, D.M.; Hammer, G.D. Wnt signaling inhibits adrenal steroidogenesis by cell-autonomous and non-cell-autonomous mechanisms. Mol. Endocrinol., 2014, 28(9), 1471-1486.
[http://dx.doi.org/10.1210/me.2014-1060] [PMID: 25029241]
[23]
Rainey, W.E.; Saner, K.; Schimmer, B.P. Adrenocortical cell lines. Mol. Cell. Endocrinol., 2004, 228(1-2), 23-38.
[http://dx.doi.org/10.1016/j.mce.2003.12.020] [PMID: 15541570]
[24]
Thomou, T.; Mori, M.A.; Dreyfuss, J.M.; Konishi, M.; Sakaguchi, M.; Wolfrum, C.; Rao, T.N.; Winnay, J.N.; Garcia-Martin, R.; Grinspoon, S.K.; Gorden, P.; Kahn, C.R. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature, 2017, 542(7642), 450-455.
[http://dx.doi.org/10.1038/nature21365] [PMID: 28199304]


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VOLUME: 13
ISSUE: 1
Year: 2020
Page: [2 - 6]
Pages: 5
DOI: 10.2174/1874467212666191015161334
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