Elevated Levels of Visfatin and Fetuin-A in Patients with Major Mental Disorders


  • Kehinde Sola Akinlade
  • Kamoru Ademola ADEDOKUN Department of Oral Pathology, DUH, King Saud University Medical City, Riyadh, Saudi Arabia.
  • Sheu Kadiri Rahamon Department of Immunology, University of Ibadan
  • Victor Olufolahan Lasebikan Department of Psychiatry, University of Ibadan


A number of cytokines are involved in the regulation of metabolic pathways. The involvement of these metabokines in the pathogenesis of metabolic dysfunction associated with major mental disorders (MMD) is presently poorly understood. This study therefore, determined the plasma levels of glucose, fetuin-A and visfatin and their inter-relationship in patients with MMD. Ninety adults consisting of 65 patients with MMD and 25 apparently healthy individuals (controls) were enrolled into this study. After an overnight fast, plasma levels of glucose, visfatin and fetuin-A were determined using the glucose-oxidase method and ELISA as appropriate. Statistical analysis was done using Kruskal Wallis, independent Student’s t-test, Mann-Whitney U and Spearman’s correlation as appropriate. P-values less than 0.05 were considered as statistically significant. Patients with MMD had significantly higher levels of fasting plasma glucose (FPG), visfatin and fetuin-A compared with the controls. Fetuin-A had a significant positive correlation with visfatin and FPG in patients with MMD. Comparing the subgroups of MMD with one another, patients with schizophrenia had a significantly higher level of visfatin compared with patients with depression. The plasma levels of fetuin-A were significantly higher in patients with schizophrenia and bipolar compared with patients with depression. It could be concluded from this study that Patients with MMD especially, those with schizophrenia and bipolar disorder have elevated levels of fetuin-A and visfatin suggesting a possible role in the pathogenesis of metabolic dysfunction associated with major mental disorders.


Adeghate, E. (2008). Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. Curr Med Chem 15(18): 1851-1862.
Akinlade, K. S., E. R. Ofagbor, S. K. Rahamon and V. O. Lasebikan. 2019. Effect of adiposity and type of antipsychotic medication on plasma levels of resistin and adiponectin in patients with major mental illnesses. Afr J Biomed Res 22: 235-239.
Akinlade, K. S., S. K. Rahamon and V. O. Lasebikan. 2018. Beta-cell function and metabolic clearance rate of glucose in Nigerians with major mental health disorders on antipsychotic drug treatment. J Natl Med Assoc 110:504-511.
Akinlade, K. S., V. O. Lasebikan, O. O. Satope and S. K. Rahamon. 2017. Risk and prevalence of type 2 diabetes mellitus in patients with major mental health disorders. East Afr Med J 94(8): 597-605.
Akinlade, K. S., O. O. Satope, V. O. Lasebikan and S. K. Rahamon. 2016. Metabolically healthy obesity and metabolic syndrome in Nigerian adults with major mental illness. Egyptian Journal of Psychiatry 37(2): 97-103.
Alexiadou, K., A. Kokkinos, S. Liatis, D. Perrea, N. Katsilambros and N. Tentolouris. 2012. Differences in plasma apelin and visfatin levels between patients with type 1 diabetes mellitus and healthy subjects and response after acute hyperglycemia and insulin administration. Hormones (Athens) 11(4): 444-450.
Alosaimi, F. D., M. Abalhassan, B. Alhaddad, N. Alzain, E. Fallata, A. Alhabbad and M. Z. Alassiry. 2017. Prevalence of metabolic syndrome and its components among patients with various psychiatric diagnoses and treatments: A cross-sectional study. Gen Hosp Psychiatry 45: 62-69.
Aroner, S. A., K. J. Mukamal, D. E. St-Jules, M. J. Budoff, R. Katz, M. H. Criqui, M. A. Allison, I. H. de Boer, D. S. Siscovick, J. H. Ix and M. K. Jensen. 2017. Fetuin-A and Risk of Diabetes Independent of Liver Fat Content: The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 185(1): 54-64.
Balhara, Y. P. 2011. Diabetes and psychiatric disorders. Indian J Endocrinol Metab 15(4): 274-283.
Basoglu, C., O. Oner, C. Gunes, U. B. Semiz, A. M. Ates, A. Algul, S. Ebrinc, M. Cetin, O. Ozcan and O. Ipcioglu. 2010. Plasma orexin A, ghrelin, cholecystokinin, visfatin, leptin and agouti-related protein levels during 6-week olanzapine treatment in first-episode male patients with psychosis. Int Clin Psychopharmacol 25(3): 165-171.
Benedict, C., A. Shostak, T. Lange, S. J. Brooks, H. B. Schioth, B. Schultes, J. Born, H. Oster and M. Hallschmid. 2012. Diurnal rhythm of circulating nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF): impact of sleep loss and relation to glucose metabolism. J Clin Endocrinol Metab 97(2): E218-222.
Bluher, M. 2014. Adipokines - removing road blocks to obesity and diabetes therapy. Mol Metab 3(3): 230-240.
Carbone, F., L. Liberale, A. Bonaventura, A. Vecchie, M. Casula, M. Cea, F. Monacelli, I. Caffa, S. Bruzzone, F. Montecucco and A. Nencioni. 2017. Regulation and Function of Extracellular Nicotinamide Phosphoribosyltransferase/Visfatin. Compr Physiol 7(2): 603-621.
Chang, Y. H., D. M. Chang, K. C. Lin, S. J. Shin and Y. J. Lee. 2011. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev 27(6): 515-527.
Dahl, T. B., S. Holm, P. Aukrust and B. Halvorsen. 2012. Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu Rev Nutr 32: 229-243.
Dahmen, N., N. Manderscheid, J. Helfrich, P. B. Musholt, T. Forst, A. Pfutzner and A. Engel. 2008. Elevated peripheral visfatin levels in narcoleptic patients. PLoS One 3(8): e2980.
Ekpe, E. L. and A. Omotoso. 2017. Visfatin and Gestational, Type 1 and Type 2 Diabetes Mellitus: A Review of Literature. Adv Biosci Clin Med 5:27-33.
Erfani, S., M. Khaksari, S. Oryan, N. Shamsaei, N. Aboutaleb, F. Nikbakht, N. Jamali-Raeufy and F. Gorjipour. 2015. Visfatin reduces hippocampal CA1 cells death and improves learning and memory deficits after transient global ischemia/reperfusion. Neuropeptides 49: 63-68.
Funk, M., N. Drew, M. Freeman, E. Faydi & World Health Organization. ‎2010‎. Mental health and development: targeting people with mental health conditions as a vulnerable group. Available: https://apps.who.int/iris/handle/10665/44257 Accessed: 11th March, 2020.
Grolla, A. A., C. Travelli, A. A. Genazzani and J. K. Sethi. 2016. Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine. Br J Pharmacol 173(14): 2182-2194.
Hammarstedt, A., J. Pihlajamäki, V. Rotter Sopasakis, S. Gogg, P. A. Jansson, M. Laakso, et al. 2006. Visfatin is an adipokine, but it is not regulated by thiazolidinediones. J Clin Endocrinol Metab 91:1181–1184.
Kocelak, P., M. Olszanecka-Glinianowicz, A. J. Owczarek, W. Krupa, P. Obirek, M. Bozentowicz-Wikarek, A. Brzozowska, M. Mossakowska, T. Zdrojewski, A. Skalska, A. Wiecek and J. Chudek. 2015. Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration in elderly subjects with metabolic syndrome. Pol Arch Med Wewn 125(6): 402-413.
Koo, M., N. S. Lai and J. K. Chiang. 2013. Short duration of sleep is associated with hyperleptinemia in Taiwanese adults. J Clin Sleep Med 9(10): 1049-1055.
Laughlin, G. A., L. K. McEvoy, E. Barrett-Connor, L. B. Daniels and J. H. Ix. 2014. Fetuin-A, a new vascular biomarker of cognitive decline in older adults. Clin Endocrinol (Oxf) 81(1): 134-140.
MacKenzie, N. E., C. Kowalchuk, S. M. Agarwal, K. A. Costa-Dookhan, F. Caravaggio, P. Gerretsen, et al. 2018. Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia. Front Psychiatry 9:622.
Mathews, S. T., N. Chellam, P. R. Srinivas, V. J. Cintron, M. A. Leon, A. S. Goustin and G. Grunberger. 2000. Alpha2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164(1-2): 87-98.
Mori, K., M. Emoto, H. Yokoyama, T. Araki, M. Teramura, H. Koyama, T. Shoji, M. Inaba and Y. Nishizawa. 2006. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29(2): 468.
Murray, R. M., P. Sham, J. Van Os, J. Zanelli, M. Cannon and C. McDonald. 2004. A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder. Schizophr Res 71(2-3): 405-416.
Ohaeri, J. U. and A. O. Akanji. 2011. Metabolic syndrome in severe mental disorders. Metab Syndr Relat Disord 9(2): 91-98.
Owashi, T. and K. Kamijima. 2012. Adverse events of antipsychotics, antidepressants, mood stabilizers, antiepileptics, and psychostimulants. Nihon Rinsho 70 Suppl 6: 279-285.
Pal, D., S. Dasgupta, R. Kundu, S. Maitra, G. Das, S. Mukhopadhyay, S. Ray, S. S. Majumdar and S. Bhattacharya. 2012. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat Med 18(8): 1279-1285.
Perez-Sotelo, D., A. Roca-Rivada, M. Larrosa-Garcia, C. Castelao, I. Baamonde, J. Baltar, A. B. Crujeiras, L. M. Seoane, F. F. Casanueva and M. Pardo. 2017. Visceral and subcutaneous adipose tissue express and secrete functional alpha2hsglycoprotein (fetuin A) especially in obesity. Endocrine 55(2): 435-446.
Revollo, J. R., A. A. Grimm and S. Imai. 2007. The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals. Curr Opin Gastroenterol 23(2): 164-170.
Shidfar, F., M. Zarrati, M. E. Khamseh, N. Haghighat, A. Rostami and H. Zolfaghari. 2014. Relationship between serum levels of fetuin-A with apo-A1, apo-B100, body composition and insulin resistance in patients with type 2 diabetes. Med J Islam Repub Iran 28: 100.
Shim, Y. S., M. J. Kang, Y. J. Oh, J. W. Baek, S. Yang and I. T. Hwang. 2017. Fetuin-A as an Alternative Marker for Insulin Resistance and Cardiovascular Risk in Prepubertal Children. J Atheroscler Thromb. 24 (10), 1031-1038.
Smith, E. R., R. Nilforooshan, G. Weaving and N. Tabet (2011). Plasma fetuin-A is associated with the severity of cognitive impairment in mild-to-moderate Alzheimer's disease. J Alzheimers Dis 24(2): 327-333.
Toalson, P., S. Ahmed, T. Hardy and G. Kabinoff. 2004. The Metabolic Syndrome in Patients With Severe Mental Illnesses. Prim Care Companion J Clin Psychiatry 6(4): 152-158.
Warren, M. W., L. S. Hynan and M. F. Weiner. 2012. Lipids and adipokines as risk factors for Alzheimer's disease. J Alzheimers Dis 29(1): 151-157.
Wędrychowicz, A., A. Zając, M. Pilecki, B. Kościelniak and P. J. Tomasik. 2014. Peptides from adipose tissue in mental disorders. World J Psychiatr 4:103–111.





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