Abstract
Aim:
Osteocalcin is involved in the progression of nonalcoholic fatty liver disease (NAFLD) in animal models and humans. In this study we investigated the relationship between serum osteocalcin levels and NAFLD in postmenopausal Chinese women.
Methods:
A total of 733 postmenopausal women (age range: 41–78 years) with normal blood glucose levels were enrolled in this cross-sectional study. Women taking lipid-lowering or anti-hypertensive drugs were excluded. Serum osteocalcin levels were assessed using an electrochemiluminescence immunoassay. The degree of NAFLD progression for each subject was assessed through ultrasonography. The fatty liver index (FLI) of each subject was calculated to quantify the degree of liver steatosis.
Results:
The median level of serum osteocalcin for all subjects enrolled was 21.99 ng/mL (interquartile range: 17.84–26.55 ng/mL). Subjects with NAFLD had significantly lower serum osteocalcin levels (18.39 ng/mL; range: 16.03–23.64 ng/mL) compared with those without NAFLD (22.31 ng/mL; range: 18.55–27.06 ng/mL; P<0.01). Serum osteocalcin levels decreased with incre¬mental changes in the FLI value divided by the quartile (P-value for trend<0.01). The serum osteocalcin levels showed a negative correlation with the FLI values, even after adjusting for confounding factors (standardized β=−0.124; P<0.01). Binary logistic regression analysis identified an individual's serum osteocalcin level as an independent risk factor for NAFLD (odds ratio: 0.951; 95% confidence interval: 0.911–0.992; P=0.02).
Conclusion:
Serum osteocalcin levels are inversely correlated with NAFLD in postmenopausal Chinese women with normal blood glucose levels.
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References
Movahed A, Larijani B, Nabipour I, Kalantarhormozi M, Asadipooya K, Vahdat K, et al. Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism. J Bone Miner Metab 2012; 30: 683–91.
Oosterwerff MM, van Schoor NM, Lips P, Eekhoff EM . Osteocalcin as a predictor of the metabolic syndrome in older persons: a population-based study. Clin Endocrinol (Oxf) 2013; 78: 242–7.
Gupte AA, Sabek OM, Fraga D, Minze LJ, Nishimoto SK, Liu JZ, et al. Osteocalcin protects against nonalcoholic steatohepatitis in a mouse model of metabolic syndrome. Endocrinology 2014; 155: 4697–705.
Yilmaz Y, Kurt R, Eren F, Imeryuz N . Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: association with ballooning degeneration. Scand J Clin Lab Invest 2011; 71: 631–6.
Liu JJ, Chen YY, Mo ZN, Tian GX, Tan AH, Gao Y, et al. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in adult males, South China. Int J Mol Sci 2013; 14: 19782–91.
Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol 2009; 161: 723–9.
Sinn DH, Gwak GY, Rhee SY, Cho J, Son HJ, Paik YH, et al. Association between serum osteocalcin levels and non-alcoholic fatty liver disease in women. Digestion 2015; 91: 150–7.
Bao Y, Ma X, Yang R, Wang F, Hao Y, Dou J, et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. J Clin Endocrinol Metab 2013; 98: 345–51.
World Health Organization. Report of a WHO Consultation: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Geneva: Switzerland, 1999.
Hao Y, Ma X, Luo Y, Shen Y, Dou J, Pan X, et al. Serum adipocyte fatty acid binding protein levels are positively associated with subclinical atherosclerosis in Chinese pre- and postmenopausal women with normal glucose tolerance. J Clin Endocrinol Metab 2014; 99: 4321–7.
Hao YP, Ma XJ, Luo YQ, Ni J, Dou JX, Hu YQ, et al. Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes. Acta Pharmacol Sin 2014; 35: 1150–6.
Fan JG . Chinese Liver Disease Association. Guidelines for management of nonalcoholic fatty liver disease: an updated and revised edition. Zhonghua Gan Zang Bing Za Zhi 2010; 18: 163–6.
Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al. The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006; 6: 33.
Targher G, Day CP, Bonora E . Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: 1341–50.
Gao X, Fan JG . Diagnosis and management of non—alcoholic fatty 1iver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology. J Diabetes 2013; 5: 406–15.
Yang R, Ma X, Pan X, Wang F, Luo Y, Gu C, et al. Serum osteocalcin levels in relation to metabolic syndrome in Chinese postmenopausal women. Menopause 2013; 20: 548–53.
Díaz-López A, Bulló M, Juanola-Falgarona M, Martínez-González MA, Estruch R, Covas MI, et al. Reduced serum concentrations of carboxylated and undercarboxylated osteocalcin are associated with risk of developing type 2 diabetes mellitus in a high cardiovascular risk population: a nested case-control study. J Clin Endocrinol Metab 2013; 98: 4524–31.
Sarkar PD, Choudhury AB . Relationships between serum osteocalcin levels versus blood glucose, insulin resistance and markers of systemic inflammation in central Indian type 2 diabetic patients. Eur Rev Med Pharmacol Sci 2013; 17: 1631–5.
Aller R, Castrillon JL, de Luis DA, Conde R, Izaola O, Sagrado MG, et al. Relation of osteocalcin with insulin resistance and histopathological changes of non alcoholic fatty liver disease. Ann Hepatol 2011; 10: 50–5.
Fernández-Real JM, Ortega F, Gómez-Ambrosi J, Salvador J, Frühbeck G, Ricart W . Circulating osteocalcin concentrations are associated with parameters of liver fat infiltration and increase in parallel to decreased liver enzymes after weight loss. Osteoporos Int 2010; 21: 2101–7.
Dou J, Ma X, Fang Q, Hao Y, Yang R, Wang F, et al. Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in Chinese men. Clin Exp Pharmacol Physiol 2013; 40: 282–8.
Auro K, Joensuu A, Fischer K, Kettunen J, Salo P, Mattsson H, et al. A metabolic view on menopause and ageing. Nat Commun 2014; 5: 4708.
Lavoie JM, Pighon A . NAFLD, estrogens, and physical exercise: The Animal Model. J Nutr Metab 2012; 2012: 914938.
Williams DC, Paul DC, Black LJ . Effects of estrogen and tamoxifen on serum osteocalcin levels in ovariectomized rats. Bone Miner 1991; 14: 205–20.
Utzschneider KM, Kahn SE . The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006; 91: 4753–61.
Chen L, Li Q, Yang Z, Ye Z, Huang Y, He M, et al. Osteocalcin, glucose metabolism, lipid profile and chronic low-grade inflammation in middle-aged and elderly Chinese. Diabet Med 2013; 30: 309–17.
Bulló M, Moreno-Navarrete JM, Fernández-Real JM, Salas-Salvadó J . Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and β cell function in elderly men at high cardiovascular risk. Am J Clin Nutr 2012; 95: 249–55.
Lucey AJ, Paschos GK, Thorsdottir I, Martínéz JA, Cashman KD, Kiely M . Young overweight and obese women with lower circulating osteocalcin concentrations exhibit higher insulin resistance and concentrations of C-reactive protein. Nutr Res 2013; 33: 67–75.
Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G . Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 2012; 50: 568–75.
Zhou B, Li H, Xu L, Zang W, Wu S, Sun H . Osteocalcin reverses endoplasmic reticulum stress and improves impaired insulin sensitivity secondary to diet-induced obesity through nuclear factor-kappaB signaling pathway. Endocrinology 2013; 154: 1055–68.
Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B . Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94: 827–32.
Hu WW, Ke YH, He JW, Fu WZ, Liu YJ, Chen D, et al. Serum osteocalcin levels are inversely associated with plasma glucose and body mass index in healthy Chinese women. Acta Pharmacol Sin 2014; 35: 1521–6.
Acknowledgements
This work was funded by a project of the National Natural Science Foundation of China (No 81170788), 973 Program of China (No 2012CB524906), the National Key Technology R&D Program of China (No 2012BAI02B03), a grant from Shanghai Health and Family Planning Commission (No 2013ZYJB1001), and a Key Science and Technology of Shanghai Project (No 13XD1403000). We appreciate the efforts of all participants who contributed to the sample measurements and data collection.
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Luo, Yq., Ma, Xj., Hao, Yp. et al. Inverse relationship between serum osteocalcin levels and nonalcoholic fatty liver disease in postmenopausal Chinese women with normal blood glucose levels. Acta Pharmacol Sin 36, 1497–1502 (2015). https://doi.org/10.1038/aps.2015.81
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DOI: https://doi.org/10.1038/aps.2015.81
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