Correlation between Extracellular Heat Shock Protein 60 (exHSP60) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Non Diabetic Men

Meiriza Djohari, Suryani As'ad, Mansyur Arif, Andi Wijaya


BACKGROUND: Adipose tissue expansion in obesity leads to abnormal adipocyte function, chronic low grade inflammation, primary reticulum stress, and mitochondrial stress. This induces mitochondrial unfolded protein response (UPRmt) that selectively upregulates mitochondrial chaperone protein. Heat shock Protein 60 (HSP60) is the primary chaperone in mitochondrial matrix. Inflammatory stress promotes HSP60 released from adipocytes and induces insulin resistance. In this study we attempted to investigate the correlation between exHSP60 and HOMA-IR in men with different ranges of waist circumference (WC).

METHODS: This study was an observational cross sectional study carried out on 141 non diabetic men, aged 30-55 years old, who were divided into three groups based on WC; WC ≤90 cm, 90 cm < WC ≤ 100 cm and WC > 100 cm. Fasting plasma glucose, triglyceride, HDL-C, hsCRP, HSP60 serum and anti-HSP60 antibody, serum IL-1β serum, insulin, were examined. For statistical analysis, Kolmogorov-Smirnov and Spearman’s correlation analysis were conducted.

RESULTS: There were a significant correlation between exHSP60 and HOMA-IR (r=0.281; p=0.041) in WC ≤ 90 cm group; and a negative significant correlation between exHSP60 and HOMA-IR (r=-0.508; p=0.007) in WC > 100 cm group.

CONCLUSION: This study showed that there was a dynamic correlation between exHSP60 and HOMA-IR in WC ≤ 90 cm group compared with WC > 100 cm group. We also found inverse correlation patterns between exHSP60 and HOMA-IR, and between anti-HSP60 antibody and HOMA-IR in non diabetic subjects.

KEYWORDS: obesity, insulin resistance, mitochondrial stress, exHSP60, hsCRP, HOMA-IR

Full Text:



Shoelson SE, Herroro L, Naaz A. Obesity, inflammation, insulin resistance. Gastroenterology. 2007; 132: 2169-80, CrossRef.

Departemen Kesehatan RI. Laporan Hasil Riset Kesehatan Dasar (RISKESDAS) Nasional 2007. Jakarta: Depkes RI; 2007, article.

Departemen Kesehatan RI. Laporan Hasil Riset Kesehatan Dasar (RISKESDAS) Nasional 2010. Jakarta: Depkes RI; 2010, article.

Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Mol Med. 2007; 14: 222-31, PMID.

Boden G. Obesity and free fatty acids (FFA). Endocrinol Metab Clin North Am. 2008; 37: 635-47, CrossRef.

De Ferranti S, Mozaffarian D. The perfect storm: Obesity, adipocyte dysfunction and metabolic consequences. Clin Chem. 2008; 54: 945-55, CrossRef.

Hu F, Liu F. Mitochondrial stress; A bridge between mitochondrial dysfunction and metabolic disease. Cell Signal. 2011; 23: 1528-33, CrossRef.

Hartl FU, Hayer-Hartl M. Molecular chaperones in cytosol: From nascent chain to folded protein. Science. 2002; 295: 1852-8, CrossRef.

Quintana FJ, Cohen IR. The HSP60 immune system network. Trends Immunol. 2011; 32: 89-95, CrossRef.

Marker T, Sell H, Zillessen P, Glode A, Kriebel J, Ouwens DM, et al. Heat shock protein 60 as a mediator of adipose tissue inflammation and insulin resistance. Diabetes. 2012; 61: 615-25, CrossRef.

Kim SC, Stice JP. Chen L, Jung JS, Gupta S, Wang Y, et al. Extracelullar heat shock protein 60, cardiac myocytes, and apoptosis. Circ Res. 2009; 105: 1186-95, CrossRef.

Wellen KE, Hotamisligil GS. Inflammation, stress and diabetes. J Clin Invest. 2005; 115: 1111-9, CrossRef.

Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006; 444: 860-7, CrossRef.

Lagathu C, Yuan-Charvet L, Bastard JP, Maachi M, Quignard-Boulange A, Capeau J, et al. Long-term treatment with interleukin-1 beta induces insulin resistance in murine and human adipocytes. Diabetolgia. 2006; 49: 2162-73, CrossRef.

Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6 and risk of developing type 2 diabetes mellitus. JAMA. 2001; 286: 327-34, CrossRef.

Barzilay JI, Abraham L, Heckbert SR, Cushman M, Kuller LH, Resnick HE, et al. The relation of markers of inflammation to the development of glucose disorders in the elderly (the Cardiovascular Health Study). Diabetes. 2001; 50: 2384-9, CrossRef.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell fuction froma fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28: 412-9, CrossRef.

Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, et al. Hyperyhrophy and/or hyperplasia: Dynamics of adipose tissue growth. PLoS Comput Biol. 2009; 5: e1000324, CrossRef.

Tripathi YB, Pandey V. Obesity and endoplasmic reticulum (ER) stresses. Front immunol. 2012; 3: 240, CrossRef.

Corydon TJ, Hansen J, Bross P, Jensen TG. Down-regulation of HSP60 expression by RNA impairs folding of medium-chain acyl-CoA dehydrogenase wild-type and disease-associated proteins. Mol Genet Metab. 2005; 85: 260-70, CrossRef.

Martin J. Molecular chaperones and mitochondrial protein folding. J Bienerg Biomembr. 1997; 29: 35-43, PMID.

Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, Ron D. Compartment specifiic perturbation of protein handling activates genes encoding mitochondrial chaperones. J Cell Sci. 2004; 117: 4055-66, CrossRef.

Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad MJ. A mitochondrial stress response in mammalian cells. EMBO J. 2002; 21: 4411-9, CrossRef.

Quintana FJ, Solomon A, Cohen IR, Nussbaum G. Induction of IgG3 to LPS via toll-like receptor 4 co-stimulation. PLoS ONE. 2008; 3: e3509, CrossRef.

Herlands RA, Christensen SR, Sweet RA, Hershberg U, Shlomchik MJ. T cell independent and toll like receptor dependent antigen driven activation of autorective B cells. Immunity. 2008; 29: 249-60, CrossRef.

Cohen-Sfady M, Nussbaum G, Pevsner-Fischer M, Mor E, Carmi P, Zanin-Zhorov A, et al. Heat shock protein 60 activates β cells via the TLR4-MyD88 pathway. J Immunol. 2005; 175: 3594-602, CrossRef.

Cohen-Sfady M, Pevsner-Fischer M, Margalit R, Cohen IR. Heat shock proten 60 via MyD88 innate signaling, protects β cells from apoptosis, spontaneous and induced. J Immunol. 2009; 183: 890-6, CrossRef.

Gupta S, Knowlton AA. HSP60 traficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol. 2007; 292: H3052-6, CrossRef.

Trayhurn P. Adipocyte biology. Obes Rev. 2007; 8 (Suppl 1): 41-4, CrossRef.

Simar D, Jacques A, Caillaud C. Heat shock proteins induction reduces stress kinases activation, potentially improving insulin signalling in monocytes from obese subjects. Cell Stress Chaperones. 2012; 17: 615-21, CrossRef.


Indexed by:






The Prodia Education and Research Institute