Reduced serum CLCF1 levels in hyperthyroidism patients and T3-treated mice

in Journal of Endocrinology
Authors:
Xuan Zhou Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Xuan Zhou in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-3494-0936
,
Yanan Zhang Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Yanan Zhang in
Current site
Google Scholar
PubMed
Close
,
Youwen Yuan Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Youwen Yuan in
Current site
Google Scholar
PubMed
Close
,
Fei Teng Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Fei Teng in
Current site
Google Scholar
PubMed
Close
,
Jiayang Lin Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Jiayang Lin in
Current site
Google Scholar
PubMed
Close
,
Xueru Ye Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Xueru Ye in
Current site
Google Scholar
PubMed
Close
,
Yaojin Pan Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Yaojin Pan in
Current site
Google Scholar
PubMed
Close
, and
Huijie Zhang Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

Search for other papers by Huijie Zhang in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0003-0640-0315

Correspondence should be addressed to H Zhang: huijie_zhang@smu.edu.cn
Restricted access
Rent on DeepDyve

Sign up for journal news

Characteristic symptoms of hyperthyroidism include weight loss, heart palpitation, and sweating. Thyroid hormones (TH) can stimulate thermogenesis through central and peripheral mechanisms. Previous studies have shown an association between dysfunction of cardiotrophin-like cytokine factor 1 (CLCF1) and cold-induced sweating syndrome, with recent research also indicating a link between CLCF1 and brown adipose tissue thermogenesis. However, it remains unclear whether CLCF1 and TH have synergistic or antagonistic effects on thermogenesis. This study aims to investigate the influence of thyroid hormone on circulating CLCF1 levels in humans and explore the potential possibilities of thyroid hormone in regulating energy metabolism by modulating Clcf1 in mice. By recruiting hyperthyroid patients and healthy subjects, we observed significantly lower serum CLCF1 levels in hyperthyroid patients compared to healthy subjects, with serum CLCF1 levels independently associated with hyperthyroidism after adjusting for potential confounders. Tissue analysis from mice treated with T3 revealed a decrease in CLCF1 expression in BAT and iWAT of C57BL/6 mice. These findings suggest that TH may play a role in regulating CLCF1 expression in adipose tissue.

 

  • Collapse
  • Expand
  • Bianco AC & & McAninch EA 2013 The role of thyroid hormone and brown adipose tissue in energy homoeostasis. Lancet. Diabetes and Endocrinology 1 250258. (https://doi.org/10.1016/S2213-8587(1370069-X)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bianco AC, Maia AL, da Silva WS & & Christoffolete MA 2005 Adaptive activation of thyroid hormone and energy expenditure. Bioscience Reports 25 191208. (https://doi.org/10.1007/s10540-005-2885-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bianco AC, Anderson G, Forrest D, Galton VA, Gereben B, Kim BW, Kopp PA, Liao XH, Obregon MJ, Peeters RP, et al.2014 American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models. Thyroid 24 88168. (https://doi.org/10.1089/thy.2013.0109)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cannon B & & Nedergaard J 2004 Brown adipose tissue: function and physiological significance. Physiological Reviews 84 277359. (https://doi.org/10.1152/physrev.00015.2003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cheng SY, Leonard JL & & Davis PJ 2010 Molecular aspects of thyroid hormone actions. Endocrine Reviews 31 139170. (https://doi.org/10.1210/er.2009-0007)

  • Ding M, Xu HY, Zhou WY, Xia YF, Li BY, Shi YJ, Dou X, Yang QQ, Qian SW, Tang Y, et al.2023 CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes. PNAS 120 e2305717120. (https://doi.org/10.1073/pnas.2305717120)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dittner C, Lindsund E, Cannon B & & Nedergaard J 2019 At thermoneutrality, acute thyroxine-induced thermogenesis and pyrexia are independent of UCP1. Molecular Metabolism 25 2034. (https://doi.org/10.1016/j.molmet.2019.05.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Harms M & & Seale P 2013 Brown and beige fat: development, function and therapeutic potential. Nature Medicine 19 12521263. (https://doi.org/10.1038/nm.3361)

  • Johann K, Cremer AL, Fischer AW, Heine M, Pensado ER, Resch J, Nock S, Virtue S, Harder L, Oelkrug R, et al.2019 Thyroid-hormone-induced browning of white adipose tissue does not contribute to thermogenesis and glucose consumption. Cell Reports 27 33853400e.3. (https://doi.org/10.1016/j.celrep.2019.05.054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johansson C, Göthe S, Forrest D, Vennström B & & Thorén P 1999 Cardiovascular phenotype and temperature control in mice lacking thyroid hormone receptor-beta or both alpha1 and beta. American Journal of Physiology 276 H2006H2012. (https://doi.org/10.1152/ajpheart.1999.276.6.H2006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, Vetrivelan R, Lu GZ, Laznik-Bogoslavski D, Hasenfuss SC, et al.2015 A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 163 643655. (https://doi.org/10.1016/j.cell.2015.09.035)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim JW, Marquez CP, Kostyrko K, Koehne AL, Marini K, Simpson DR, Lee AG, Leung SG, Sayles LC, Shrager J, et al.2019 Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma. Nature Medicine 25 17831795. (https://doi.org/10.1038/s41591-019-0612-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Klein J, Fasshauer M, Ito M, Lowell BB, Benito M & & Kahn CR 1999 beta(3)-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes. Journal of Biological Chemistry 274 3479534802. (https://doi.org/10.1074/jbc.274.49.34795)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Krause K 2020 Novel aspects of white adipose tissue browning by thyroid hormones. Experimental and Clinical Endocrinology & Diabetes 128 446449. (https://doi.org/10.1055/a-1020-5354)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li M, Chen Y, Jiang J, Lu Y, Song Z, Zhang S, Sun C, Ying H, Fan X, Song Y, et al.2019 Elevated serum neuregulin 4 levels in patients with hyperthyroidism. Endocrine Connections 8 728735. (https://doi.org/10.1530/EC-19-0175)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu S, Shen S, Yan Y, Sun C, Lu Z, Feng H, Ma Y, Tang Z, Yu J, Wu Y, et al.2022a Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation. Nature Communications 13 3394. (https://doi.org/10.1038/s41467-022-31154-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu T, Wang Q, Zhou L, Zhang P, Mi L, Qiu X, Chen Z, Kuang H, Li S & & Lin JD 2022b Intrahepatic paracrine signaling by cardiotrophin-like cytokine factor 1 ameliorates diet-induced NASH in mice. Hepatology 78 14781491. (https://doi.org/10.1002/hep.32719)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Martínez-Sánchez N, Moreno-Navarrete JM, Contreras C, Rial-Pensado E, Fernø J, Nogueiras R, Diéguez C, Fernández-Real JM & & López M 2017 Thyroid hormones induce browning of white fat. Journal of Endocrinology 232 351362. (https://doi.org/10.1530/JOE-16-0425)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Masini M, De Tata V, Del Roso A, Simonetti I, Pollera M & & Bergamini E 1990 The brown adipose tissue of hyperthyroid rats. A biochemical and ultrastructural study. Molecular and Cellular Endocrinology 73 2734. (https://doi.org/10.1016/0303-7207(9090041-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nedergaard J & & Cannon B 2010 The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metabolism 11 268272. (https://doi.org/10.1016/j.cmet.2010.03.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rehnmark S, Kopecký J, Jacobsson A, Néchad M & Herron D , Nelson BD, Obregon MJ, Nedergaard J & & Cannon B 1989 Brown adipocytes differentiated in vitro can express the gene for the uncoupling protein thermogenin: effects of hypothyroidism and norepinephrine. Experimental Cell Research 182 7583. (https://doi.org/10.1016/0014-4827(8990280-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ribeiro MO, Carvalho SD, Schultz JJ, Chiellini G, Scanlan TS, Bianco AC & & Brent GA 2001 Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific. Journal of Clinical Investigation 108 97105. (https://doi.org/10.1172/JCI12584)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ribeiro MO, Bianco SDC, Kaneshige M, Schultz JJ, Cheng SY, Bianco AC & & Brent GA 2010 Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis. Endocrinology 151 432440. (https://doi.org/10.1210/en.2009-0667)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rousseau F, Gauchat JF, McLeod JG, Chevalier S, Guillet C, Guilhot F, Cognet I, Froger J, Hahn AF, Knappskog PM, et al.2006 Inactivation of cardiotrophin-like cytokine, a second ligand for ciliary neurotrophic factor receptor, leads to cold-induced sweating syndrome in a patient. PNAS 103 1006810073. (https://doi.org/10.1073/pnas.0509598103)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Senaldi G, Varnum BC, Sarmiento U, Starnes C, Lile J, Scully S, Guo J, Elliott G, McNinch J, Shaklee CL, et al.1999 Novel neurotrophin-1/B cell-stimulating factor-3: a cytokine of the IL-6 family. PNAS 96 1145811463. (https://doi.org/10.1073/pnas.96.20.11458)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Senaldi G, Stolina M, Guo J, Faggioni R, McCabe S, Kaufman SA, Van G, Xu W, Fletcher FA, Boone T, et al.2002 Regulatory effects of novel neurotrophin-1/b cell-stimulating factor-3 (cardiotrophin-like cytokine) on B cell function. Journal of Immunology 168 56905698. (https://doi.org/10.4049/jimmunol.168.11.5690)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Silva JE 2003 The thermogenic effect of thyroid hormone and its clinical implications. Annals of Internal Medicine 139 205213. (https://doi.org/10.7326/0003-4819-139-3-200308050-00010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taylor PN, Albrecht D, Scholz A, Gutierrez-Buey G, Lazarus JH, Dayan CM & & Okosieme OE 2018 Global epidemiology of hyperthyroidism and hypothyroidism. Nature Reviews. Endocrinology 14 301316. (https://doi.org/10.1038/nrendo.2018.18)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Teixeira PFDS, Dos Santos PB & & Pazos-Moura CC 2020 The role of thyroid hormone in metabolism and metabolic syndrome. Therapeutic Advances in Endocrinology and Metabolism 11 2042018820917869. (https://doi.org/10.1177/2042018820917869)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vlotides G, Zitzmann K, Stalla GK & & Auernhammer CJ 2004 Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3)/cardiotrophin-like cytokine (CLC)--a novel gp130 cytokine with pleiotropic functions. Cytokine and Growth Factor Reviews 15 325336. (https://doi.org/10.1016/j.cytogfr.2004.04.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang S, Hu X, Ma L, Zhang L & & Tian Y 2022 CLCF1 is up-regulated in renal ischemia reperfusion injury and may associate with FOXO3. Annals of Translational Medicine 10 399. (https://doi.org/10.21037/atm-21-4381)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Weiner J, Hankir M, Heiker JT, Fenske W & & Krause K 2017 Thyroid hormones and browning of adipose tissue. Molecular and Cellular Endocrinology 458 156159. (https://doi.org/10.1016/j.mce.2017.01.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wikström L, Johansson C, Saltó C, Barlow C, Campos Barros A, Baas F, Forrest D, Thorén P & & Vennström B 1998 Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO Journal 17 455461. (https://doi.org/10.1093/emboj/17.2.455)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xiao F, Lin M, Huang P, Zeng J, Zeng X, Zhang H, Li X, Yang S, Li Z & & Li X 2015 Elevated serum fibroblast growth factor 21 levels in patients with hyperthyroidism. Journal of Clinical Endocrinology and Metabolism 100 38003805. (https://doi.org/10.1210/jc.2015-1797)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yau WW & & Yen PM 2020 Thermogenesis in adipose tissue activated by thyroid hormone. International Journal of Molecular Sciences 21 3020. (https://doi.org/10.3390/ijms21083020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yau WW, Singh BK, Lesmana R, Zhou J, Sinha RA, Wong KA, Wu Y, Bay BH, Sugii S, Sun L, et al.2019 Thyroid hormone (T) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy. Autophagy 15 131150. (https://doi.org/10.1080/15548627.2018.1511263)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yuan Y, Li K, Ye X, Wen S, Zhang Y, Teng F, Zhou X, Deng Y, Yang X, Wang W, et al.2024 CLCF1 inhibits energy expenditure via suppressing brown fat thermogenesis. PNAS 121 e2310711121. (https://doi.org/10.1073/pnas.2310711121)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG & & Barres BA 2012 Genomic analysis of reactive astrogliosis. Journal of Neuroscience 32 63916410. (https://doi.org/10.1523/JNEUROSCI.6221-11.2012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang J & & Lazar MA 2000 The mechanism of action of thyroid hormones. Annual Review of Physiology 62 439466. (https://doi.org/10.1146/annurev.physiol.62.1.439)

  • Zhao J, Li M, Chen Y, Zhang S, Ying H, Song Z, Lu Y, Li X, Xiong X & & Jiang J 2018 Elevated serum growth differentiation factor 15 levels in hyperthyroid patients. Frontiers in Endocrinology 9 793. (https://doi.org/10.3389/fendo.2018.00793)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zou X, Bolon B, Pretorius JK, Kurahara C, McCabe J, Christiansen KA, Sun N, Duryea D, Foreman O, Senaldi G, et al.2009 Neonatal death in mice lacking cardiotrophin-like cytokine is associated with multifocal neuronal hypoplasia. Veterinary Pathology 46 514519. (https://doi.org/10.1354/vp.08-VP-0239-B-BC)

    • PubMed
    • Search Google Scholar
    • Export Citation