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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Adiponectin is Inversely Associated with Insulin Resistance in Adolescents with Nonalcoholic Fatty Liver Disease

Author(s): Bin Liu*, Huan Zheng*, Guanghui Liu and Zhiling Li*

Volume 22, Issue 6, 2022

Published on: 01 February, 2022

Page: [631 - 639] Pages: 9

DOI: 10.2174/1871530321666210927153831

Price: $65

Abstract

Background: Insulin Resistance (IR) is confirmed as a key feature of Nonalcoholic Fatty Liver Disease (NAFLD) in children and adolescents. Numerous studies report that adiponectin (APN) levels are inversely associated with the status of IR in adults with NAFLD. This study aimed to investigate the relationship between serum total APNand Homeostasis Model Assessment Insulin Resistance (HOMA-IR) in adolescents with NAFLD.

Methods: 382 newly-diagnosed NAFLD adolescents, aged 9-16 years old, were enrolled and divided into three subgroups according to the APNtertile. Simple and multiple linear regression analyses were performed to assess the correlation between HOMA-IR and APN in boys and girls, respectively.

Results: The HOMA-IR values tended to decrease in boys according to APN tertiles: 5.6(4.4-7.3) vs. 5.2(4.6-6.9) vs. 4.9(4.1-5.8) (p<0.01), and there was a significant difference in the HOMA-IR values among three APN tertile subgroups in girls (p<0.01). Univariate analysis showed that body mass index, waist circumference, weight-to-height ratio, fasting blood glucose, insulin, triglyceride, and APN were significantly associated with HOMA-IR in boys (p<0.05). In girls, body mass index, fasting blood glucose, insulin, total cholesterol, triglyceride, and APN were significantly associated with HOMA-IR (p<0.05).APN was found to be a significant determinant for HOMA-IR only in boys (β=-0.147, p<0.01).

Conclusion: Our findings showed that APN was an independent and significant determinant for increased HOMA-IR in boys with NAFLD. Further studies are needed to explore the underlying mechanisms.

Keywords: Adiponectin, insulin resistance, nonalcoholic fatty liver disease, adolescent, homeostasis model assessment of insulin resistance, adipokines.

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[1]
Day, C.P.; James, O.F. Steatohepatitis: A tale of two "hits"? Gastroenterology, 1998, 114(4), 842-845.
[http://dx.doi.org/10.1016/S0016-5085(98)70599-2]
[2]
Fang, Y.L.; Chen, H.; Wang, C.L.; Liang, L. Pathogenesis of non-alcoholic fatty liver. World J. Gastroenterol, 2018, 24(27), 2974-2983.
[3]
Conjeevaram Selvakumar, P.K.; Kabbany, M.N.; Alkhouri, N. Nonalcoholic fatty liver disease in children: Not a small matter. Paediatr. Drugs, 2018, 20(4), 315-329.
[http://dx.doi.org/10.1007/s40272-018-0292-2] [PMID: 29740791]
[4]
Song, P.; Yu, J.; Wang, M.; Chang, X.; Wang, J.; An, L. Prevalence and correlates of suspected nonalcoholic fatty liver disease in Chinese children. Int. J. Environ. Res. Public Health, 2017, 14(5), 465.
[http://dx.doi.org/10.3390/ijerph14050465] [PMID: 28448433]
[5]
Montecucco, F.; Mach, F. Does non-alcoholic fatty liver disease (NAFLD) increase cardiovascular risk? Endocr. Metab. Immune Disord. Drug Targets, 2008, 8(4), 301-307.
[http://dx.doi.org/10.2174/187153008786848268] [PMID: 19075784]
[6]
Targher, G.; Chonchol, M.B.; Byrne, C.D. CKD and nonalcoholic fatty liver disease. Am. J. Kidney Dis., 2014, 64(4), 638-652.
[http://dx.doi.org/10.1053/j.ajkd.2014.05.019] [PMID: 25085644]
[7]
Gaggini, M.; Morelli, M.; Buzzigoli, E.; DeFronzo, R.A.; Bugianesi, E.; Gastaldelli, A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients, 2013, 5(5), 1544-1560.
[http://dx.doi.org/10.3390/nu5051544] [PMID: 23666091]
[8]
Ighbariya, A.; Weiss, R. Insulin resistance, prediabetes, metabolic syndrome: What should every pediatrician know? J. Clin. Res. Pediatr. Endocrinol., 2017, 9(Suppl. 2), 49-57.
[PMID: 29280741]
[9]
Tang, Q.; Li, X.; Song, P.; Xu, L. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future. Drug Discov. Ther., 2015, 9(6), 380-385.
[http://dx.doi.org/10.5582/ddt.2015.01207] [PMID: 26781921]
[10]
Fujii, H.; Imajo, K.; Yoneda, M.; Nakahara, T.; Hyogo, H.; Takahashi, H.; Hara, T.; Tanaka, S.; Sumida, Y.; Eguchi, Y.; Chayama, K.; Nakajima, A.; Nishimoto, N.; Kawada, N. HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol., 2019, 34(8), 1390-1395.
[http://dx.doi.org/10.1111/jgh.14595] [PMID: 30600551]
[11]
Polyzos, S.A.; Kountouras, J.; Mantzoros, C.S. Adipokines in nonalcoholic fatty liver disease. Metabolism, 2016, 65(8), 1062-1079.
[http://dx.doi.org/10.1016/j.metabol.2015.11.006] [PMID: 26725002]
[12]
Obata, Y.; Yamada, Y.; Takahi, Y.; Baden, M.Y.; Saisho, K.; Tamba, S.; Yamamoto, K.; Umeda, M.; Furubayashi, A.; Matsuzawa, Y. Relationship between serum adiponectin levels and age in healthy subjects and patients with type 2 diabetes. Clin. Endocrinol. (Oxf.), 2013, 79(2), 204-210.
[http://dx.doi.org/10.1111/cen.12041] [PMID: 22963459]
[13]
Orlando, A.; Nava, E.; Giussani, M.; Genovesi, S. Adiponectin and cardiovascular risk. From pathophysiology to clinic: focus on children and adolescents. Int. J. Mol. Sci., 2019, 20(13), 3228.
[http://dx.doi.org/10.3390/ijms20133228] [PMID: 31262082]
[14]
Polyzos, S.A.; Toulis, K.A.; Goulis, D.G.; Zavos, C.; Kountouras, J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism, 2011, 60(3), 313-326.
[http://dx.doi.org/10.1016/j.metabol.2010.09.003] [PMID: 21040935]
[15]
Farrell, G.C.; Chitturi, S.; Lau, G.K.; Sollano, J.D. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J. Gastroenterol. Hepatol., 2007, 22(6), 775-777.
[http://dx.doi.org/10.1111/j.1440-1746.2007.05002.x] [PMID: 17565629]
[16]
Gastaldelli, A.; Kozakova, M.; Højlund, K.; Flyvbjerg, A.; Favuzzi, A.; Mitrakou, A.; Balkau, B. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology, 2009, 49(5), 1537-1544.
[http://dx.doi.org/10.1002/hep.22845] [PMID: 19291789]
[17]
Dongiovanni, P.; Rametta, R.; Meroni, M.; Valenti, L. The role of insulin resistance in nonalcoholic steatohepatitis and liver disease development-a potential therapeutic target? Expert Rev. Gastroenterol. Hepatol., 2016, 10(2), 229-242.
[http://dx.doi.org/10.1586/17474124.2016.1110018] [PMID: 26641143]
[18]
Brown, M.S.; Goldstein, J.L. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab., 2008, 7(2), 95-96.
[http://dx.doi.org/10.1016/j.cmet.2007.12.009] [PMID: 18249166]
[19]
Jelenik, T.; Kaul, K.; Séquaris, G.; Flögel, U.; Phielix, E.; Kotzka, J.; Knebel, B.; Fahlbusch, P.; Hörbelt, T.; Lehr, S.; Reinbeck, A.L.; Müller-Wieland, D.; Esposito, I.; Shulman, G.I.; Szendroedi, J.; Roden, M. Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver. Diabetes, 2017, 66(8), 2241-2253.
[http://dx.doi.org/10.2337/db16-1147] [PMID: 28490610]
[20]
Korenblat, K.M.; Fabbrini, E.; Mohammed, B.S.; Klein, S. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology, 2008, 134(5), 1369-1375.
[http://dx.doi.org/10.1053/j.gastro.2008.01.075] [PMID: 18355813]
[21]
European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia, 2016, 59(6), 1121-1140.
[http://dx.doi.org/10.1007/s00125-016-3902-y] [PMID: 27053230]
[22]
Yoo, J.; Lee, S.; Kim, K.; Yoo, S.; Sung, E.; Yim, J. Relationship between insulin resistance and serum alanine aminotransferase as a surrogate of NAFLD (nonalcoholic fatty liver disease) in obese Korean children. Diabetes Res. Clin. Pract., 2008, 81(3), 321-326.
[http://dx.doi.org/10.1016/j.diabres.2008.05.006] [PMID: 18571268]
[23]
Kelishadi, R.; Cook, S.R.; Amra, B.; Adibi, A. Factors associated with insulin resistance and non-alcoholic fatty liver disease among youths. Atherosclerosis, 2009, 204(2), 538-543.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.09.034] [PMID: 19013572]
[24]
Goss, A.M.; Dowla, S.; Pendergrass, M.; Ashraf, A.; Bolding, M.; Morrison, S.; Amerson, A.; Soleymani, T.; Gower, B. Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial. Pediatr. Obes., 2020, 15(7), e12630.
[http://dx.doi.org/10.1111/ijpo.12630] [PMID: 32128995]
[25]
Meng, L.; Luo, N.; Mi, J. Impacts of types and degree of obesity on non-alcoholic fatty liver disease and related dyslipidemia in Chinese school-age children? Biomed. Environ. Sci., 2011, 24(1), 22-30.
[http://dx.doi.org/10.1111/ijpo.12630] [PMID: 21440836]
[26]
Hernández, M.J.G.; Klünder, M.; Nieto, N.G.; Alvarenga, J.C.L.; Gil, J.V.; Huerta, S.F.; Siccha, R.Q.; Hernandez, J. Pediatric viseral adiposity index adaptation correlates with HOMA-IR, Matsuda, and transminases. Endocr. Pract., 2018, 24(3), 294-301.
[http://dx.doi.org/10.4158/EP-2017-0086] [PMID: 29547047]
[27]
Mager, D.R.; Yap, J.; Rodriguez-Dimitrescu, C.; Mazurak, V.; Ball, G.; Gilmour, S. Anthropometric measures of visceral and subcutaneous fat are important in the determination of metabolic dysregulation in boys and girls at risk for nonalcoholic fatty liver disease. Nutr. Clin. Pract., 2013, 28(1), 101-111.
[http://dx.doi.org/10.1177/0884533612454884] [PMID: 23042833]
[28]
Rashid, M.; Roberts, E.A. Nonalcoholic steatohepatitis in children. J. Pediatr. Gastroenterol. Nutr., 2000, 30(1), 48-53.
[http://dx.doi.org/10.1097/00005176-200001000-00017] [PMID: 10630439]
[29]
Mager, D.R.; Ling, S.; Roberts, E.A. Anthropometric and metabolic characteristics in children with clinically diagnosed nonalcoholic fatty liver disease. Paediatr. Child Health, 2008, 13(2), 111-117.
[PMID: 19183714]
[30]
Mohamed, R.Z.; Jalaludin, M.Y.; Anuar Zaini, A. Predictors of non-alcoholic fatty liver disease (NAFLD) among children with obesity. J. Pediatr. Endocrinol. Metab., 2020, 33(2), 247-253.
[http://dx.doi.org/10.1515/jpem-2019-0403] [PMID: 31926095]
[31]
Yang, S.; Zhong, J.; Ye, M.; Miao, L.; Lu, G.; Xu, C.; Xue, Z.; Zhou, X. Association between the non-HDL-cholesterol to HDL-cholesterol ratio and non-alcoholic fatty liver disease in Chinese children and adolescents: a large single-center cross-sectional study. Lipids Health Dis., 2020, 19(1), 242.
[http://dx.doi.org/10.1186/s12944-020-01421-5] [PMID: 33222696]
[32]
Fang, H.; Judd, R.L. Adiponectin regulation and function. Compr. Physiol., 2018, 8(3), 1031-1063.
[http://dx.doi.org/10.1002/cphy.c170046] [PMID: 29978896]
[33]
Polyzos, S.A.; Kountouras, J.; Zavos, C.; Tsiaousi, E. The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease. Diabetes Obes. Metab., 2010, 12(5), 365-383.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01176.x] [PMID: 20415685]
[34]
Zhang, H.; Niu, Y.; Gu, H.; Lu, S.; Zhang, W.; Li, X.; Yang, Z.; Qin, L.; Su, Q. Low serum adiponectin is a predictor of progressing to nonalcoholic fatty liver disease. J. Clin. Lab. Anal., 2019, 33(3), e22709.
[http://dx.doi.org/10.1002/jcla.22709] [PMID: 30390352]
[35]
Lebensztejn, D.M.; Wojtkowska, M.; Skiba, E.; Werpachowska, I.; Tobolczyk, J.; Kaczmarski, M. Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease. Adv. Med. Sci., 2009, 54(2), 177-182.
[http://dx.doi.org/10.2478/v10039-009-0047-y] [PMID: 20022856]
[36]
Boyraz, M.; Cekmez, F.; Karaoglu, A.; Cinaz, P.; Durak, M.; Bideci, A. Serum adiponectin, leptin, resistin and RBP4 levels in obese and metabolic syndrome children with nonalcoholic fatty liver disease. Biomarkers Med., 2013, 7(5), 737-745.
[http://dx.doi.org/10.2217/bmm.13.13] [PMID: 24044566]
[37]
Shabalala, S.C.; Dludla, P.V.; Mabasa, L.; Kappo, A.P.; Basson, A.K.; Pheiffer, C.; Johnson, R. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed. Pharmacother., 2020, 131, 110785.
[http://dx.doi.org/10.1016/j.biopha.2020.110785] [PMID: 33152943]
[38]
Combs, T.P.; Marliss, E.B. Adiponectin signaling in the liver. Rev. Endocr. Metab. Disord., 2014, 15(2), 137-147.
[http://dx.doi.org/10.1007/s11154-013-9280-6] [PMID: 24297186]
[39]
Ballestri, S.; Nascimbeni, F.; Baldelli, E.; Marrazzo, A.; Romagnoli, D.; Lonardo, A. NAFLD as a sexual dimorphic disease: Role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv. Ther., 2017, 34(6), 1291-1326.
[http://dx.doi.org/10.1007/s12325-017-0556-1] [PMID: 28526997]
[40]
Denzer, C.; Thiere, D.; Muche, R.; Koenig, W.; Mayer, H.; Kratzer, W.; Wabitsch, M. Gender-specific prevalences of fatty liver in obese children and adolescents: roles of body fat distribution, sex steroids, and insulin resistance. J. Clin. Endocrinol. Metab., 2009, 94(10), 3872-3881.
[http://dx.doi.org/10.1210/jc.2009-1125] [PMID: 19773396]
[41]
Villanueva-Ortega, E.; Garcés-Hernández, M.J.; Herrera-Rosas, A.; López-Alvarenga, J.C.; Laresgoiti-Servitje, E.; Escobedo, G.; Queipo, G.; Cuevas-Covarrubias, S.; Garibay-Nieto, G.N. Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population. Ann. Hepatol., 2019, 18(5), 693-700.
[http://dx.doi.org/10.1016/j.aohep.2019.04.012] [PMID: 31151875]
[42]
Africa, J.A.; Newton, K.P.; Schwimmer, J.B. Lifestyle interventions including nutrition, exercise, and supplements for nonalcoholic fatty liver disease in children. Dig. Dis. Sci., 2016, 61(5), 1375-1386.
[http://dx.doi.org/10.1007/s10620-016-4126-1] [PMID: 27041377]
[43]
Nielsen, M.S.; Quist, J.S.; Chaput, J.P.; Dalskov, S.M.; Damsgaard, C.T.; Ritz, C.; Astrup, A.; Michaelsen, K.F.; Sjödin, A.; Hjorth, M.F. Physical activity, sedentary Time, and sleep and the association with inflammatory markers and adiponectin in 8- to 11-year-old Danish children. J. Phys. Act. Health, 2016, 13(6), 733-739.
[http://dx.doi.org/10.1123/jpah.2015-0123] [PMID: 26800571]

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