Association between inflammatory markers, BDNF, MCP-1 levels and insulin resistance in obese premenopausal women

Moushira Zaki


The present study deals with the investigation of serum TNF-α, IL-6, brain derived neurotrophic factor (BDNF), monocyte chemo-attractant and protein1 (MCP-1), fasting glucose and serum insulin levels of apparently healthy Egyptian premenopausal obese  women and compared with healthy non obese control women. This study aimed to determine assoction between inflammatory markers, BDNF, MCP-1, obesity measures and insulin resistance (IR) risk. The study included 120 apparently healthy Egyptian women, 60 obese and 60 non- obese. IR has been estimated by the Homeostasis Model Insulin Resistance (HOMA-IR). Results showed marked elevation in inflammatory markers and MCP-1 in obese women than controls. Significant reduction of BDNF levels was observed in obese cases with significant negative correlations with obesity measures and HOMA-IR and positive relations with TNF-α and MCP-1. In conclusion our data demonstrated increase of inflammatory markers and MCP-1 as well as decrease of BDNF levels in obese women, suggesting that these biomarkers might be positional candidate linking obesity markers that play important role for development of IR in apparently healthy Egyptian obese premenopausal women.

Full Text:



Zhang HH, Halbleib M, Ahmad F, Manganiello VC, Greenberg AS. Tumor necrosis factor-α stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes 2002;51:2929–35.

Chaldakov G. The metabotrophic NGF and BDNF: an emerging concept. Arch Ital Biol 2011;149:257–63.

Chaldakov GN, Fiore M, Ranćić G, Beltowski J, Tunçel N, Aloe L. An integrated view: Neuroadipocrinology of diabesity. Serbian J Exp Clin Res 2014;15:61–9.

Xu B, Xie X. Neurotrophic factor control of satiety and body weight. Nat Rev Neurosci 2016;17:282.

Amadio P, Colombo GI, Tarantino E, Gianellini S, Ieraci A, Brioschi M, et al. BDNFVal66met polymorphism: a potential bridge between depression and thrombosis. Eur Heart J 2015;38:1426–35.

Singh RB, Takahashi T, Tokunaga M, Wilczynska A, Kim CJ, Meester F De, et al. Effect of brain derived neurotrophic factor, in relation to diet and lifestyle factors, for prevention of neuropsychiatric and vascular diseases and diabetes. Open Nutraceuticals J 2014;7.

Lebrun B, Bariohay B, Moyse E, Jean A. Brain-derived neurotrophic factor (BDNF) and food intake regulation: a minireview. Auton Neurosci 2006;126:30–8.

Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 2014;25:89–98.

Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 2003;6:736.

Bariohay B, Lebrun B, Moyse E, Jean A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex. Endocrinology 2005;146:5612–20.

Motamedi S, Karimi I, Jafari F. The interrelationship of metabolic syndrome and neurodegenerative diseases with focus on brain-derived neurotrophic factor (BDNF): Kill two birds with one stone. Metab Brain Dis 2017;32:651–65.

Das UN. Obesity: genes, brain, gut, and environment. Nutrition 2010;26:459–73.

Yao Y, Tsirka SE. Monocyte chemoattractant protein-1 and the blood–brain barrier. Cell Mol Life Sci 2014;71:683–97.

Ding T, Sun J, Zhang P. Study on MCP-1 related to inflammation induced by biomaterials. Biomed Mater 2009;4:35005.

Hirschler V, Oestreicher K, Maccallini G, Aranda C. Relationship between obesity and metabolic syndrome among Argentinean elementary school children. Clin Biochem 2010;43:435–41.

Zaki M, Kholoussi S, Ismail S, Abdel H, Helwa I, Hassan N, et al. Obesity in relation to inflammatory biomarkers , adiponectin gene variability , and insulin resistance among middle-aged Egyptian women 2015:70–6. doi:10.1097/01.MXE.0000465684.75400.25.

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

El-Gharbawy AH, Adler-Wailes DC, Mirch MC, Theim KR, Ranzenhofer L, Tanofsky-Kraff M, et al. Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents. J Clin Endocrinol Metab 2006;91:3548–52.

Corripio R, Gónzalez‐Clemente J, Jacobo P, Silvia N, Lluis G, Joan V, et al. Plasma brain‐derived neurotrophic factor in prepubertal obese children: results from a 2‐year lifestyle intervention programme. Clin Endocrinol (Oxf) 2012;77:715–20.

Roth CL, Elfers C, Gebhardt U, Müller HL, Reinehr T. Brain-derived neurotrophic factor and its relation to leptin in obese children before and after weight loss. Metabolism 2013;62:226–34.

Kheirouri S, Haghighi S, Saidpour A. Brain-derived neurotrophic factor in obese women and its relationship with leptin and ghrelin. Prog Nutr 2017;19:169–75.

Lee I-T, Lee W-J, Tsai I-C, Liang K-W, Lin S-Y, Wan C-J, et al. Brain-derived neurotrophic factor not associated with metabolic syndrome but inversely correlated with vascular cell adhesion molecule-1 in men without diabetes. Clin Chim Acta 2012;413:944–8.

Sandrini L, Di Minno A, Amadio P, Ieraci A, Tremoli E, Barbieri S. Association between obesity and circulating brain-derived neurotrophic factor (BDNF) levels: Systematic review of literature and meta-analysis. Int J Mol Sci 2018;19:2281.

Gajewska E, Sobieska M, Łojko D, Wieczorowska-Tobis K, Suwalska A. Obesity itself does not influence BDNF serum levels in adults. Eur Rev Med Pharmacol Sci 2014;18:3246–50.

Silha J V, Krsek M, Skrha J V, Sucharda P, Nyomba BL, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003;149:331–5.

Gray J, Yeo GSH, Cox JJ, Morton J, Adlam A-LR, Keogh JM, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes 2006;55:3366–71.

Hristova MG. Metabolic syndrome–From the neurotrophic hypothesis to a theory. Med Hypotheses 2013;81:627–34.

Sobieska M, Gajewska E, Kalmus G, Samborski W. Obesity, physical fitness, and inflammatory markers in Polish children. Med Sci Monit Int Med J Exp Clin Res 2013;19:493.

Huang C-J, Mari DC, Whitehurst M, Slusher A, Wilson A, Shibata Y. Brain-derived neurotrophic factor expression ex vivo in obesity. Physiol Behav 2014;123:76–9.

Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci 2003;100:7265–70.

Perreault M, Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 2001;7:1138.

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

Catalán V, Gómez-Ambrosi J, Ramirez B, Rotellar F, Pastor C, Silva C, et al. Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg 2007;17:1464–74.

Lee Y, Lee S-H, Jung ES, Kim J-S, Shim CY, Ko Y-G, et al. Visceral adiposity and the severity of coronary artery disease in middle-aged subjects with normal waist circumference and its relation with lipocalin-2 and MCP-1. Atherosclerosis 2010;213:592–7.

Kelly KR, Haus JM, Solomon TPJ, Patrick-Melin AJ, Cook M, Rocco M, et al. A low-glycemic index diet and exercise intervention reduces TNFα in isolated mononuclear cells of older, obese adults. J Nutr 2011;141:1089–94.

Younce CW, Azfer A, Kolattukudy PE. MCP-1 (monocyte chemotactic protein-1)-induced protein, a recently identified zinc finger protein, induces adipogenesis in 3T3-L1 pre-adipocytes without peroxisome proliferator-activated receptor γ. J Biol Chem 2009;284:27620–8.

Chacón MR, Fernández‐Real JM, Richart C, Megía A, Gómez JM, Miranda M, et al. Monocyte chemoattractant protein‐1 in obesity and type 2 diabetes. Insulin sensitivity study. Obesity 2007;15:664–72.

Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes 2005;29:146.

Bruun JM, Lihn AS, Madan AK, Pedersen SB, Schiøtt KM, Fain JN, et al. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Metab 2004;286:E8–13.

Kim CS, Park HS, Kawada T, Kim JH, Lim D, Hubbard NE, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes 2006;30:1347.


  • There are currently no refbacks.