Circulating THBS1: A Risk Factor for Nonalcoholic Fatty Liver Disease in Obese Children

Annals of Nutrition and Metabolism

Basic/Transitional Science: Research Article

Li M.a· Liu L.a· Kang Y.a· Huang S.b· Xiao Y.a

Author affiliations

aDepartment of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
bDepartment of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing Of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Basic/Transitional Science: Research Article

Received: July 06, 2022
Accepted: October 22, 2022
Published online: October 28, 2022

Number of Print Pages: 13
Number of Figures: 4
Number of Tables: 4

ISSN: 0250-6807 (Print)
eISSN: 1421-9697 (Online)

For additional information: https://www.karger.com/ANM

Abstract

Introduction: Thrombospondin 1 (THBS1) is a highly expressed adipokine in adults with obesity. In the present study, we aimed to investigate the clinical significance of THBS1in children with obesity and nonalcoholic fatty liver disease (NAFLD) and determine the effect of metformin on THBS1 expression in dietary-induced obese (DIO) mice. Methods: A cross-sectional study was conducted among 78 obese children and 35 nonobese children. Anthropometric parameters, clinical data, and circulating THBS1 levels were measured. The expression of THBS1 was detected in the serum and liver tissue from diet-induced obese mice (C57BL/6) with or without metformin treatment. Results: Higher THBS1 levels were observed in children with NAFLD and higher SDS-BMI. Individuals in the higher THBS1 quartile had a higher prevalence of hypo-high-density lipoprotein cholesterol (HDL-C). Logistic regression analysis showed a significant correlation between THBS1 and NAFLD, as well as between hip circumference and leptin levels. Receiver-operating characteristic (ROC) analysis revealed that THBS1 was a more sensitive predictor of NAFLD than leptin. Additionally, metformin ameliorated hepatic steatosis and decreased hepatic THBS1 expression in high-fat diet (HFD)-fed mice. Conclusions: Circulating THBS1 level may be a risk factor for NAFLD in obese children. Our findings provided a novel approach of metformin administration for the prevention and treatment of NAFLD. This study also confirmed that metformin decreased the expression of hepatic THBS in DIO mice.

© 2022 S. Karger AG, Basel

References Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. Mayo Clin Proc. 2017 Feb;92(2):251–65. Drozdz D, Alvarez-Pitti J, Wójcik M, Borghi C, Gabbianelli R, Mazur A, et al. Obesity and cardiometabolic risk factors: from childhood to adulthood. Nutrients. 2021 Nov 22;13(11):4176. Eslam M, Alkhouri N, Vajro P, Baumann U, Weiss R, Socha P, et al. Defining paediatric metabolic (dysfunction)-associated fatty liver disease: an international expert consensus statement. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):864–73. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018 Jan;15(1):11–20. Zhou X, Hou DQ, Duan JL, Sun Y, Cheng H, Zhao XY, et al. Prevalence of nonalcoholic fatty liver disease and metabolic abnormalities in 387 obese children and adolescents in Beijing, China. Zhonghua Liu Xing Bing Xue Za Zhi. 2013 May;34(5):446–50. Bornstein P. Thrombospondins as matricellular modulators of cell function. J Clin Invest. 2001 Apr;107(8):929–34. Kong P, Gonzalez-Quesada C, Li N, Cavalera M, Lee DW, Frangogiannis NG. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation. Am J Physiol Endocrinol Metab. 2013 Aug 1;305(3):E439–50. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, et al. Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes. 2008 Feb;57(2):432–9. Inoue M, Jiang Y, Barnes RH 2nd, Tokunaga M, Martinez-Santibañez G, Geletka L, et al. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice. Endocrinology. 2013 Dec;154(12):4548–59. Min-DeBartolo J, Schlerman F, Akare S, Wang J, McMahon J, Zhan Y, et al. Thrombospondin-I is a critical modulator in non-alcoholic steatohepatitis (NASH). PLoS One. 2019;14(12):e0226854. Hopkins BD, Goncalves MD, Cantley LC. Obesity and cancer mechanisms: cancer metabolism. J Clin Oncol. 2016 Dec 10;34(35):4277–83. Lv Z, Guo Y. Metformin and its benefits for various diseases. Front Endocrinol. 2020;11:191. Szymczak-Pajor I, Wenclewska S, Śliwińska A. Metabolic action of metformin. Pharmaceuticals. 2022 Jun 30;15(7):810. Tan BK, Adya R, Chen J, Farhatullah S, Heutling D, Mitchell D, et al. Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1. Cardiovasc Res. 2009 Aug 1;83(3):566–74. Han X, Tao Y, Deng Y, Yu J, Sun Y, Jiang G. Metformin accelerates wound healing in type 2 diabetic db/db mice. Mol Med Rep. 2017 Dec;16(6):8691–8. Ji CY; Working Group on Obesity in China. Report on childhood obesity in China (1): body mass index reference for screening overweight and obesity in Chinese school-age children. Biomed Environ Sci. 2005 Dec;18(6):390–400. Consortium T. Recommended standards for assessing blood pressure in human research where blood pressure or hypertension is a major focus. Clin Exp Hypertens. 2018;40(6):509–13. Tan X, Wang X, Chu H, Liu H, Yi X, Xiao Y. SFRP5 correlates with obesity and metabolic syndrome and increases after weight loss in children. Clin Endocrinol. 2014 Sep;81(3):363–9. Li M, Wang M, Liu Y, Huang S, Yi X, Yin C, et al. TNF-Α upregulates IKKε expression via the Lin28B/let-7a pathway to induce catecholamine resistance in adipocytes. Obesity. 2019 May;27(5):767–76. Li M, Sharma A, Yin C, Tan X, Xiao Y. Metformin ameliorates hepatic steatosis and improves the induction of autophagy in HFD-induced obese mice. Mol Med Rep. 2017 Jul;16(1):680–6. Liang L, Fu JF, DU JB. Significance of exploring the definition of metabolic syndrome in Chinese children and adolescents. Zhonghua Er Ke Za Zhi. 2012 Jun;50(6):401–4. Yin C, Zhang H, Zhang M, Xiao Y. Adropin and apelin-12 efficiently predict metabolic syndrome in obese children. Pediatr Diabetes. 2020 Nov;21(7):1132–9. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011 Mar;53(3):810–20. Matsuo Y, Tanaka M, Yamakage H, Sasaki Y, Muranaka K, Hata H, et al. Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome. Metabolism. 2015 Nov;64(11):1490–9. Bai J, Xia M, Xue Y, Ma F, Cui A, Sun Y, et al. Thrombospondin 1 improves hepatic steatosis in diet-induced insulin-resistant mice and is associated with hepatic fat content in humans. EBioMedicine. 2020 Jul;57:102849. Gwag T, Reddy Mooli RG, Li D, Lee S, Lee EY, Wang S. Macrophage-derived thrombospondin 1 promotes obesity-associated non-alcoholic fatty liver disease. JHEP Rep. 2021 Feb;3(1):100193. Tahergorabi Z, Salmani F, Jonaidabad SH, Behdani B, Yazdi P, Zardast M, et al. Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study. Obstet Gynecol Sci. 2019 Nov;62(6):420–8. Buras ED, Converso-Baran K, Davis CS, Akama T, Hikage F, Michele DE, et al. Fibro-adipogenic remodeling of the diaphragm in obesity-associated respiratory dysfunction. Diabetes. 2019 Jan;68(1):45–56. McCarthy JJ, Meyer J, Moliterno DJ, Newby LK, Rogers WJ, Topol EJ. Evidence for substantial effect modification by gender in a large-scale genetic association study of the metabolic syndrome among coronary heart disease patients. Hum Genet. 2003 Dec;114(1):87–98. Lin CH, Kohli R. Emerging new diagnostic modalities and therapies of nonalcoholic fatty liver disease. Curr Gastroenterol Rep. 2020 Aug 19;22(10):52. Jiménez-Cortegana C, García-Galey A, Tami M, Del Pino P, Carmona I, López S, et al. Role of leptin in non-alcoholic fatty liver disease. Biomedicines. 2021 Jun 30;9(7):762. Chavez RJ, Haney RM, Cuadra RH, Ganguly R, Adapala RK, Thodeti CK, et al. Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle cells via JAK2- and MAPK-dependent pathways. Am J Physiol Cell Physiol. 2012 Jul 15;303(2):C179–91. Gonzalez-Quesada C, Cavalera M, Biernacka A, Kong P, Lee DW, Saxena A, et al. Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix in addition to promoting vascular rarefaction through angiopoietin-2 upregulation. Circ Res. 2013 Dec 6;113(12):1331–44. Sahu S, Ganguly R, Raman P. Leptin augments recruitment of IRF-1 and CREB to thrombospondin-1 gene promoter in vascular smooth muscle cells in vitro. Am J Physiology-Cell Physiol. 2016 Aug 1;311(2):C212–24. Ganguly R, Khanal S, Mathias A, Gupta S, Lallo J, Sahu S, et al. TSP-1 (Thrombospondin-1) deficiency protects ApoE(-/-) mice against leptin-induced atherosclerosis. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):e112–27. Roth JJ, Gahtan V, Brown JL, Gerhard C, Swami VK, Rothman VL, et al. Thrombospondin-1 is elevated with both intimal hyperplasia and hypercholesterolemia. J Surg Res. 1998 Jan;74(1):11–6. Hida K, Wada J, Zhang H, Hiragushi K, Tsuchiyama Y, Shikata K, et al. Identification of genes specifically expressed in the accumulated visceral adipose tissue of OLETF rats. J Lipid Res. 2000 Oct;41(10):1615–22. Kerforne T, Favreau F, Khalifeh T, Maiga S, Allain G, Thierry A, et al. Hypercholesterolemia-induced increase in plasma oxidized LDL abrogated pro angiogenic response in kidney grafts. J Transl Med. 2019 Jan 14;17(1):26. Kong P, Cavalera M, Frangogiannis NG. The role of thrombospondin (TSP)-1 in obesity and diabetes. Adipocyte. 2014 Jan 1;3(1):81–4. Chavez-Tapia NC, Rosso N, Tiribelli C. Effect of intracellular lipid accumulation in a new model of non-alcoholic fatty liver disease. BMC Gastroenterol. 2012 Mar 1;12:20. Li Y, Tong X, Rumala C, Clemons K, Wang S. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model. PLoS One. 2011;6(10):e26656. Soliman A, De Sanctis V, Alaaraj N, Hamed N. The clinical application of metformin in children and adolescents: a short update. Acta Biomed. 2020 Sep 7;91(3):e2020086. Article / Publication Details

First-Page Preview

Abstract of Basic/Transitional Science: Research Article

Received: July 06, 2022
Accepted: October 22, 2022
Published online: October 28, 2022

Number of Print Pages: 13
Number of Figures: 4
Number of Tables: 4

ISSN: 0250-6807 (Print)
eISSN: 1421-9697 (Online)

For additional information: https://www.karger.com/ANM

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif