TNF-α ASSOCIATED FREE FATTY ACID FLUX AND ITS CONTRIBUTION TO INSULIN RESISTANCE AND ATHEROGENIC DYSLIPIDEMIA: A CROSS-SECTIONAL STUDY
Main Article Content
Keywords
Tumor necrosis factor-alpha, free fatty acids, insulin resistance, atherogenic dyslipidemia, metabolic syndrome
Abstract
Tumor necrosis factor-alpha (TNF-α) plays a critical role in metabolic dysfunction by stimulating lipolysis and increasing free fatty acid (FFA) flux, contributing to insulin resistance and atherogenic dyslipidemia. This study investigated the association between TNF-α levels, FFA concentrations, insulin resistance, and lipid profile abnormalities in Indian patients with metabolic disorders.
Methods: A cross-sectional study was conducted at Maa Vindhyavasini Autonomous State Medical College, Mirzapur, from March 2025 to August 2025. A total of 142 participants were recruited using consecutive sampling, comprising type 2 diabetes mellitus patients (n=50), metabolic syndrome patients (n=47), and healthy controls (n=45). Anthropometric measurements, glycemic parameters, serum TNF-α, FFA levels, and lipid profiles were assessed. Insulin resistance was calculated using homeostatic model assessment (HOMA-IR). Statistical analyses included ANOVA, correlation analysis, and multiple regression.
Results: TNF-α levels were significantly elevated in diabetic (24.8±8.6 pg/mL) and metabolic syndrome groups (18.4±6.2 pg/mL) compared to controls (8.6±3.4 pg/mL, p<0.001). FFA concentrations showed similar patterns (0.78±0.24, 0.62±0.18, and 0.38±0.12 mmol/L respectively, p<0.001). Strong positive correlations were observed between TNF-α and FFA levels (r=0.742, p<0.001), HOMA-IR (r=0.684, p<0.001), and triglycerides (r=0.656, p<0.001). Atherogenic dyslipidemia prevalence reached 82% in diabetics and 70.2% in metabolic syndrome patients.
Conclusion: Elevated TNF-α levels demonstrated significant associations with increased FFA flux, insulin resistance, and atherogenic dyslipidemia, supporting the inflammatory-metabolic axis in disease pathogenesis. These findings emphasize the importance of targeting inflammatory pathways in metabolic disorder management.
References
• Deepa, R., Velmurugan, K., Arvind, K., Sivaram, P., Sientay, C., Uday, S., & Mohan, V. (2006). Serum levels of interleukin 6, C-reactive protein, vascular cell adhesion molecule 1, and monocyte chemotactic protein 1 in relation to insulin resistance and glucose intolerance—the Chennai Urban Rural Epidemiology Study (CURES). Metabolism, 55(9), 1232-1238. https://doi.org/10.1016/j.metabol.2006.05.008
• Donnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J. (2005). Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. Journal of Clinical Investigation, 115(5), 1343-1351. https://doi.org/10.1172/JCI23621
• Ginsberg, H. N., Zhang, Y. L., & Hernandez-Ono, A. (2005). Regulation of plasma triglycerides in insulin resistance and diabetes. Archives of Medical Research, 36(3), 232-240. https://doi.org/10.1016/j.arcmed.2005.01.005
• Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860-867. https://doi.org/10.1038/nature05485
• Hotamisligil, G. S. (2017). Inflammation, metaflammation and immunometabolic disorders. Nature, 542(7640), 177-185. https://doi.org/10.1038/nature21363
• Joshi, S. R., Anjana, R. M., Deepa, M., Pradeepa, R., Bhansali, A., Dhandania, V. K., ... & Mohan, V. (2007). Prevalence of dyslipidemia in urban and rural India: The ICMR-INDIAB study. PLoS One, 9(5), e96808. https://doi.org/10.1371/journal.pone.0096808
• Kapoor, D., Iqbal, R., Singh, K., Jamal, J., & Kumar, S. (2012). Efficacy of telmisartan in reducing the levels of inflammatory markers in metabolic syndrome: A double-blind, randomized, placebo-controlled study. Indian Journal of Pharmacology, 44(3), 336-341. https://doi.org/10.4103/0253-7613.96310
• Karpe, F., Dickmann, J. R., & Frayn, K. N. (2011). Fatty acids, obesity, and insulin resistance: Time for a reevaluation. Diabetes, 60(10), 2441-2449. https://doi.org/10.2337/db11-0425
• Kulkarni, K. R. (2012). Cholesterol profile measurement by vertical auto profile method. Clinics in Laboratory Medicine, 26(4), 787-802. https://doi.org/10.1016/j.cll.2006.07.004
• Misra, A., & Khurana, L. (2008). Obesity and the metabolic syndrome in developing countries. Journal of Clinical Endocrinology & Metabolism, 93(11 Supplement 1), S9-S30. https://doi.org/10.1210/jc.2008-1595
• Misra, A., Tandon, N., Ebrahim, S., Sattar, N., Alam, D., Shrivastava, U., ... & Bhardwaj, S. (2017). Diabetes, cardiovascular disease, and chronic kidney disease in South Asia: Current status and future directions. BMJ, 357, j1420. https://doi.org/10.1136/bmj.j1420
• Mohan, V., Deepa, R., Rani, S. S., & Premalatha, G. (2005). Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). Journal of the American College of Cardiology, 38(3), 682-687. https://doi.org/10.1016/S0735-1097(01)01415-2
• Mohan, V., Shah, S., & Saboo, B. (2007). Current glycemic status and diabetes related complications among type 2 diabetes patients in India: Data from the A1chieve study. Journal of the Association of Physicians of India, 61(Suppl), 12-15.
• Pradeepa, R., & Mohan, V. (2017). Prevalence of type 2 diabetes and its complications in India and economic costs to the nation. European Journal of Clinical Nutrition, 71(7), 816-824. https://doi.org/10.1038/ejcn.2017.40
• Pradhan, A. D., Manson, J. E., Rifai, N., Buring, J. E., & Ridker, P. M. (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA, 286(3), 327-334. https://doi.org/10.1001/jama.286.3.327
• Ramachandran, A., Snehalatha, C., Mary, S., Mukesh, B., Bhaskar, A. D., & Vijay, V. (2006). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia, 49(2), 289-297. https://doi.org/10.1007/s00125-005-0097-z
• Ross, R., Dagnone, D., Jones, P. J., Smith, H., Paddags, A., Hudson, R., & Janssen, I. (2000). Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: A randomized, controlled trial. Annals of Internal Medicine, 133(2), 92-103. https://doi.org/10.7326/0003-4819-133-2-200007180-00008
• Ruan, H., Miles, P. D., Ladd, C. M., Ross, K., Golub, T. R., Olefsky, J. M., & Lodish, H. F. (2002). Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-alpha: Implications for insulin resistance. Diabetes, 51(11), 3176-3188. https://doi.org/10.2337/diabetes.51.11.3176
• Ryden, M., & Arner, P. (2007). Tumour necrosis factor-alpha in human adipose tissue—from signalling mechanisms to clinical implications. Journal of Internal Medicine, 262(4), 431-438. https://doi.org/10.1111/j.1365-2796.2007.01854.x
• Samuel, V. T., & Shulman, G. I. (2012). Mechanisms for insulin resistance: Common threads and missing links. Cell, 148(5), 852-871. https://doi.org/10.1016/j.cell.2012.02.017
• Stanley, T. L., Zanni, M. V., Johnsen, S., Rasheed, S., Makimura, H., Lee, H., ... & Grinspoon, S. K. (2011). TNF-α antagonism with etanercept decreases glucose and increases the proportion of high molecular weight adiponectin in obese subjects with features of the metabolic syndrome. Journal of Clinical Endocrinology & Metabolism, 96(1), E146-E150. https://doi.org/10.1210/jc.2010-1170
• Taskinen, M. R. (2003). Diabetic dyslipidaemia: From basic research to clinical practice. Diabetologia, 46(6), 733-749. https://doi.org/10.1007/s00125-003-1111-y
• Unger, R. H., & Orci, L. (2002). Lipoapoptosis: Its mechanism and its diseases. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1585(2-3), 202-212. https://doi.org/10.1016/S1388-1981(02)00342-6
• Wajchenberg, B. L. (2000). Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome. Endocrine Reviews, 21(6), 697-738. https://doi.org/10.1210/edrv.21.6.0415
• Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., ... & Chen, H. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 112(12), 1821-1830. https://doi.org/10.1172/JCI200319451
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Dr. Jaipal Singh
Associate Professor, Department of Biochemistry, Maa Vindhyavasini Autonomous State Medical College, Mirzapur, Uttar Pradesh
Dr. Ajit Thakur
Associate Professor, Department of Biochemistry, Veer Chandra Singh Garhwali Government Institute of Medical Science & Research, Srinagar, Uttarakhand
Dr. Ankit Singh
Assistant Professor, Department of Community Medicine, Autonomous State Medical College, Sonebhadra, Uttar Pradesh
