Browse > Article
http://dx.doi.org/10.14348/molcells.2017.0073

A Proteomics Based Approach Reveals Differential Regulation of Visceral Adipose Tissue Proteins between Metabolically Healthy and Unhealthy Obese Patients  

Alfadda, Assim A. (Obesity Research Center, College of Medicine, King Saud University)
Masood, Afshan (Obesity Research Center, College of Medicine, King Saud University)
Al-Naami, Mohammed Y. (Department of Surgery, College of Medicine, King Saud University)
Chaurand, Pierre (Department of Chemistry, Universite de Montreal)
Benabdelkamel, Hicham (Obesity Research Center, College of Medicine, King Saud University)
Publication Information
Molecules and Cells / v.40, no.9, 2017 , pp. 685-695 More about this Journal
Abstract
Obesity and the metabolic disorders that constitute metabolic syndrome are a primary cause of morbidity and mortality in the world. Nonetheless, the changes in the proteins and the underlying molecular pathways involved in the relevant pathogenesis are poorly understood. In this study a proteomic analysis of the visceral adipose tissue isolated from metabolically healthy and unhealthy obese patients was used to identify presence of altered pathway(s) leading to metabolic dysfunction. Samples were obtained from 18 obese patients undergoing bariatric surgery and were subdivided into two groups based on the presence or absence of comorbidities as defined by the International Diabetes Federation. Two dimensional difference in-gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was carried out. A total of 28 proteins were identified with a statistically significant difference in abundance and a 1.5-fold change (ANOVA, $p{\leq}0.05$) between the groups. 11 proteins showed increased abundance while 17 proteins were decreased in the metabolically unhealthy obese compared to the healthy obese. The differentially expressed proteins belonged broadly to three functional categories: (i) protein and lipid metabolism (ii) cytoskeleton and (iii) regulation of other metabolic processes. Network analysis by Ingenuity pathway analysis identified the $NF{\kappa}B$, IRK/MAPK and PKC as the nodes with the highest connections within the connectivity map. The top network pathway identified in our protein data set related to cellular movement, hematological system development and function, and immune cell trafficking. The VAT proteome between the two groups differed substantially between the groups which could potentially be the reason for metabolic dysfunction.
Keywords
healthy obese; metabolic syndrome; obesity; proteomics; visceral adipose tissue; unhealthy obese;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Schleiff, E., Shore, G.C., and Goping, I.S. (1997). Human mitochondrial import receptor, Tom20p. Use of glutathione to reveal specific interactions between Tom20-glutathione S-transferase and mitochondrial precursor proteins. FEBS Lett. 404, 314-318.   DOI
2 Shevchenko, A., Wilm, M., Vorm, O., and Mann, M. (1996). Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68, 850-858.   DOI
3 Smith, H.W., and Marshall, C.J. (2010). Regulation of cell signalling by uPAR. Nat. Rev. Mol. Cell Biol. 11, 23-36.   DOI
4 van Vliet-Ostaptchouk, J.V., Nuotio, M.L., Slagter, S.N., Doiron, D., Fischer, K., Foco, L., Gaye, A., Gogele, M., Heier, M., Hiekkalinna, T., et al. (2014). The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies. BMC Endocr. Disord. 14, 9.   DOI
5 Wen, Y., Edelman, J.L., Kang, T., and Sachs, G. (1999). Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1. Biochem. Biophys. Res. Commun. 258, 713-721.   DOI
6 Xu, S.P., Mao, X.Y., Ren, F.Z. and Che, H.L. (2011). Attenuating effect of casein glycomacropeptide on proliferation, differentiation, and lipid accumulation of in vitro Sprague-Dawley rat preadipocytes. J. Dairy Sci. 94, 676-683.   DOI
7 Zemany, L., Bhanot, S., Peroni, O.D., Murray, S.F., Moraes-Vieira, P.M., Castoldi, A., Manchem, P., Guo, S., Monia, B.P., and Kahn, B.B. (2015). Transthyretin antisense oligonucleotides lower circulating RBP4 levels and improve insulin sensitivity in obese mice. Diabetes 64, 1603-1614.   DOI
8 Alfadda, A.A. (2014). Circulating adipokines in healthy versus unhealthy overweight and obese subjects. Int. J. Endocrinol. 2014, 170434.
9 Alfadda, A.A., Benabdelkamel, H., Masood, A., Moustafa, A., Sallam, R., Bassas, A., and Duncan, M. (2013). Proteomic analysis of mature adipocytes from obese patients in relation to aging. Exp. Gerontol. 48, 1196-1203.   DOI
10 Badoud, F., Perreault, M., Zulyniak, M.A., and Mutch, D.M. (2015). Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 29, 748-758.   DOI
11 Benabdelkamel, H., Masood, A., Almidani, G.M., Alsadhan, A.A., Bassas, A.F., Duncan, M.W., and Alfadda, A.A. (2015). Mature adipocyte proteome reveals differentially altered protein abundances between lean, overweight and morbidly obese human subjects. Mol. Cell. Endocrinol. 401, 142-154.   DOI
12 Gurnell, M., Savage, D.B., Chatterjee, V.K., and O'Rahilly, S. (2003). The metabolic syndrome: peroxisome proliferator-activated receptor gamma and its therapeutic modulation. J. Clin. Endocrinol. Metabol. 88, 2412-2421.   DOI
13 Bluher, M. (2014). Are metabolically healthy obese individuals really healthy? Eur. J. Endocrinol. 171, R209-219.   DOI
14 Bohm, A., Halama, A., Meile, T., Zdichavsky, M., Lehmann, R., Weigert, C., Fritsche, A., Stefan, N., Konigsrainer, A., Haring, H.U., et al. (2014). Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. PLoS One 9, e93148.   DOI
15 Doumatey, A.P., Zhou, J., Zhou, M., Prieto, D., Rotimi, C.N., and Adeyemo, A. (2016). Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study. Obesity (Silver Spring). 24, 1257-1265.   DOI
16 Fabbrini, E., Yoshino, J., Yoshino, M., Magkos, F., Tiemann Luecking, C., Samovski, D., Fraterrigo, G., Okunade, A.L., Patterson, B.W., and Klein, S. (2015). Metabolically normal obese people are protected from adverse effects following weight gain. J. Clin. Invest. 125, 787-795.   DOI
17 Gomez-Serrano, M., Camafeita, E., Garcia-Santos, E., Lopez, J.A., Rubio, M.A., Sanchez-Pernaute, A., Torres, A., Vazquez, J., and Peral, B. (2016). Proteome-wide alterations on adipose tissue from obese patients as age-, diabetes- and gender-specific hallmarks. Sci. Rep. 6, 25756.   DOI
18 Hwang, Y.C., Hayashi, T., Fujimoto, W.Y., Kahn, S.E., Leonetti, D.L., McNeely, M.J., and Boyko, E.J. (2015). Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype. Int. J. Obes. 39, 1365-1370.   DOI
19 He, J., and Baum, L.G. (2006). Galectin interactions with extracellular matrix and effects on cellular function. Methods Enzymol. 417, 247-256.
20 Hodges, B.D., and Wu, C.C. (2010). Proteomic insights into an expanded cellular role for cytoplasmic lipid droplets. J. Lipid Res. 51, 262-273.   DOI
21 Juhan-Vague, I., Alessi, M.C., Mavri, A., and Morange, P.E. (2003). Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J. Thrombosis Haemostasis 1, 1575-1579.   DOI
22 Kramer, C.K., Zinman, B., and Retnakaran, R. (2013). Are metabolically healthy overweight and obesity benign conditions?: a systematic review and meta-analysis. Ann. Int. Med. 159, 758-769.   DOI
23 Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., Margono, C., Mullany, E.C., Biryukov, S., Abbafati, C., Abera, S.F., et al. (2014). Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384, 766-781.   DOI
24 Lackey, D.E., Burk, D.H., Ali, M.R., Mostaedi, R., Smith, W.H., Park, J., Scherer, P.E., Seay, S.A., McCoin, C.S., Bonaldo, P., et al. (2014). Contributions of adipose tissue architectural and tensile properties toward defining healthy and unhealthy obesity. Am. J. Physiol. Endocrinol. Metabol. 306, E233-246.   DOI
25 Marsich, E., Mozetic, P., Ortolani, F., Contin, M., Marchini, M., Vetere, A., Pacor, S., Semeraro, S., Vittur, F., and Paoletti, S. (2008). Galectin- 1 in cartilage: expression, influence on chondrocyte growth and interaction with ECM components. Matrix Biol. 27, 513-525.   DOI
26 Mori, S., Kiuchi, S., Ouchi, A., Hase, T., and Murase, T. (2014). Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue. Int. J. Biol. Sci. 10, 825-833.   DOI
27 Murri, M., Insenser, M., Bernal-Lopez, M.R., Perez-Martinez, P., Escobar-Morreale, H.F., and Tinahones, F.J. (2013). Proteomic analysis of visceral adipose tissue in pre-obese patients with type 2 diabetes. Mol. Cell. Endocrinol. 376, 99-106.   DOI
28 Musgrove, J.P. (1990). Family and community health in a new medical school. Med. Education 24, 124-128.   DOI
29 O'Brien, L., Hosick, P.A., John, K., Stec, D.E., and Hinds, T.D., Jr. (2015). Biliverdin reductase isozymes in metabolism. Trends Endocrinol. Metabol. 26, 212-220.   DOI
30 Oliva, K., Barker, G., Rice, G.E., Bailey, M.J., and Lappas, M. (2013). 2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue. J. Endocrinol. 218, 165-178.   DOI
31 Rothhut, B., Dubois, T., Feliers, D., Russo-Marie, F., and Oudinet, J.P. (1995). Inhibitory effect of annexin V on protein kinase C activity in mesangial cell lysates. Eur. J. Biochem. 232, 865-872.   DOI
32 Olofsson, S.O., Bostrom, P., Andersson, L., Rutberg, M., Perman, J., and Boren, J. (2009). Lipid droplets as dynamic organelles connecting storage and efflux of lipids. Biochim. Biophys. Acta 1791, 448-458.   DOI
33 Ouchi, N., Parker, J.L., Lugus, J.J., and Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 11, 85-97.   DOI
34 Pataky, Z., Bobbioni-Harsch, E., and Golay, A. (2010). Open questions about metabolically normal obesity. Int. J. Obes. 34 Suppl 2, S18-23.
35 Peinado, J.R., Pardo, M., de la Rosa, O., and Malagon, M.M. (2012). Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity. Proteomics 12, 607-620.   DOI
36 Reaven, G.M. (2011). The metabolic syndrome: time to get off the merry-go-round? J. Int. Med. 269, 127-136.   DOI
37 Sato, H., Ogata, H., and De Luca, L.M. (2000). Annexin V inhibits the 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/extracellular signal-regulated kinase (ERK). signaling pathway upstream of Shc in MCF-7 cells. Oncogene 19, 2904-2912.   DOI
38 Scarpulla, R.C. (2008). Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol. Rev. 88, 611-638.   DOI
39 Schleiff, E., and McBride, H. (2000). The central matrix loop drives import of uncoupling protein 1 into mitochondria. J. Cell Sci. 113 ( Pt 12), 2267-2272.