Obesity Research

Open journal

ISSN 2377-8385

Adipocytokines: A Potential Link Between Obesity and CNS Disorders

Nadia Hafizi, Elham Alipoor and Mohammad Javad Hosseinzadeh-Attar*

Mohammad Javad Hosseinzadeh-Attar

Professor School of Nutritional Sciences and Dietetics Tehran University of Medical Sciences No#44, Hojjatdoost St., Naderi Ave., Keshavarz Bld., Tehran, Iran; Tel. +982188993059; Fax: +982188984861; E-mail: mhosseinzadeh@tums.ac.ir

The interrelationships between obesity and high fat mass with different chronic pathophysiological conditions have been taken into consideration in recent decades along with the growing prevalence of obesity. Epidemiological evidence supports the increased risk of the onset and progression of cardiovascular disease (CVD), hypertension, dyslipidemia, type 2 diabetes and some types of cancers with obesity.1 Studies in neurological disorders have also suggested the potential contribution of obesity in developing structural pathologies in the brain in different life stages.2

Obesity can induce atrophic changes in vulnerable areas of the brain including hippocampus, cingulate gyrus and frontal lobes, which in turn could be a risk factor for Alzheimer’s disease (AD).3,4 Age-related deficits such as decline in immediate memory function have also been exacerbated with higher body mass index (BMI) and abdominal obesity especially in people with AD.5 Furthermore, the risk of dementia is 2.34 to 3.60 fold higher in obese people with a waist circumference above recommended cut offs.6 Although, the exact mechanisms by which obesity could influence the CNS are not fully understood, they may involve many mediators including systemic and brain peptides and cytokines.7 In 2009, it has been confirmed that circulating inflammatory cytokines might mediate the effect of midlife obesity on brain gray matter reduction in pre- and post-menopausal women.8

Adipocytes can produce and release some water soluble peptides, adipocytokines, such as leptin, resistin, adiponectin, visfatin,9 inflammatory cytokines including tumor necrosis factor alpha, transforming growth factor beta, and interleukins (e.g., IL-1, IL-6, IL-10 and IL8), and some components of the complement system.10 White adipose tissue deposition may lead to systemic inflammatory state due the imbalance between pro- and anti-inflammatory adipocytokines.11 Obesity associated inflammation could be deleterious for blood brain barrier (BBB) integrity and predispose of penetration of inflammatory molecules. Abnormal increased concentration of inflammatory cytokines in the local micro-environment of brain parenchyma would be a major contributor of neurological disorders.12,13

Adiponectin almost exclusively synthesized by adipocytes. It is well described as an insulin-sensitizing, anti-atherogenic, and anti-inflammatory agent.14 Serum concentrations of adiponectin may reflect its cerebrospinal fluid (CSF) levels.15 Brain expression of adiponectin receptors, AdipoR1 and AdipoR2, suggests that adiponectin signaling could participate in neurological pathways16; however, the precise role of this adipokine in CNS disorders is not clear. While various studies suggest that decrease in serum levels of adiponectin is associated with cognitive dysfunction, others did not find any clear relationship between adiponectin levels and AD progression.17 In addition, it has been reported that low serum levels of adiponectin may increase the risk of multiple sclerosis (MS).17 Although, adiponectin levels remained unchanged in some investigations in Parkinson’s disease (PD),18,19 other studies supported a protective effect of treatment with recombinant adiponectin against neurodegeneration.20 It seems that understanding the relationship between adiponectin with neurodegenerative and CVD is complex and requires more studies.

Visfatin is another major adipocytokine, which is strongly correlated with visceral fat mass and higher BMI.21 The pro-inflammatory properties of visfatin could stimulate other inflammatory cytokines, which in turn might induce some inflammatory disorders.22,23 Serum level of visfatin is associated with ischemic stroke24 and the consequences of traumatic brain injury.25 Hallschmid et al26 showed that CSF level of visfatin decreased with fat accumulation, which could indicate damage of visfatin transfer system across BBB. Visfatin might have unfavorable effects on CNS and promote damages to dopaminergic neurons and brain regions such as cortex and hippocampus. Visfatin induced pathological changes in the brain structures that would be accompanied with higher risk of neurodegenerative diseases including AD and PD.27

There are also other studies discussing the potential role of other adipocytokines including leptin and resistin in CNS. However, the data obtained from studies on adipocytokines in neurological disorders are still contradictory and unclear. Considering the increasing number of newly identified adipokines and adipocytokines, and their possible link with the onset or exacerbation of neurological diseases, is a great field of study to investigate the potential causative, diagnostic or therapeutic role of these adipose derived peptides in CNS disorders.


The authors declare that they have no conflicts of interest.

1. WHO Consultation on Obesity. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 2000: 1-253.

2. Bruce-Keller AJ, Keller JN, Morrison CD. Obesity and vulnerability of the CNS. Biochim Biophys Acta. 2009; 1792(5): 395-400. doi: 10.1016/j.bbadis.2008.10.004

3. Gustafson D, Lissner L, Bengtsson C, Bjorkelund C, Skoog I. A 24-year follow-up of body mass index and cerebral atrophy. Neurology. 2004; 63(10): 1876-1881. doi: 10.1212/01.WNL.0000141850.47773.5F

4. Pannacciulli N, Del Parigi A, Chen K, Le DS, Reiman EM, Tataranni PA. Brain abnormalities in human obesity: A voxel-based morphometric study. Neuroimage. 2006; 31(4): 1419-1425. doi: 10.1016/j.neuroimage.2006.01.047

5. Birdsill AC, Carlsson CM, Willette AA, et al. Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity (Silver Spring). 2013; 21(7): 1313-1320. doi: 10.1002/oby.20170

6. Whitmer RA, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson EP, Yaffe K. Central obesity and increased risk of dementia more than three decades later. Neurology. 2008; 71(14): 1057-1064. doi: 10.1212/01.wnl.0000306313.89165.ef

7. Fotuhi M, Lubinski B. The effects of obesity on brain structure and size. Pract Neurol. 2013: 20-29. Website. http://practicalneurology.com/2013/08/the-effects-of-obesity-on-brain-structure-and-size/. Accessed April 3, 2017.

8. Soreca I, Rosano C, Jennings JR, et al. Gain in adiposity across 15 years is associated with reduced gray matter volume in healthy women. Psychosom Med. 2009; 71(5): 485-490. doi: 10.1097/PSY.0b013e3181a5429d

9. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115(5): 911-919. doi: 10.1016/j. jaci.2005.02.023

10. Gerhardt CC, Romero IA, Cancello R, Camoin L, Strosberg AD. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol. 2001; 175(1-2): 81-92. doi: 10.1016/S0303-7207(01)00394-X

11. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol. 2004; 25(1): 4-7. doi: 10.1016/j.it.2003.10.013

12. Tucsek Z, Toth P, Sosnowska D, et al. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: Effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol A Biol Sci Med Sci. 2014; 69(10): 1212-1226. doi: 10.1093/gerona/glt177 

13. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci. 2011; 12(12): 723-738. doi: 10.1038/nrn3114

14. Turer AT, Scherer PE. Adiponectin: Mechanistic insights and clinical implications. Diabetologia. 2012; 55(9): 2319-2326. doi: 10.1007/s00125-012-2598-x

15. Une K, Takei YA, Tomita N, et al. Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease. Eur J Neurol. 2011; 18(7): 1006-1009. doi: 10.1111/j.1468-1331.2010.03194.x

16. Qiu G, Wan R, Hu J, et al. Adiponectin protects rat hippocampal neurons against excitotoxicity. Age (Dordr). 2011; 33(2): 155- 165. doi: 10.1007/s11357-010-9173-5

17. Yang Y, Hu W, Jiang S, et al. The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases. Biochim Biophys Acta. 2015; 1852(9): 1887-1894. doi: 10.1016/j.bbadis.2015.06.019

18. Aziz NA, Pijl H, Frolich M, Roelfsema F, Roos RA. Leptin, adiponectin, and resistin secretion and diurnal rhythmicity are unaltered in Parkinson’s disease. Mov Disord. 2011; 26(4): 760-761. doi: 10.1016/j.bbadis.2015.06.019

19. Cassani E, Cancello R, Cavanna F, et al. Serum adiponectin levels in advanced-stage Parkinson’s disease patients. Parkinsons Dis. 2011; 2011: 624764. doi: 10.4061/2011/624764

20. Holscher C. New drug treatments show neuroprotective effects in Alzheimer’s and Parkinson’s diseases. Neural Regen Res. 2014; 9(21): 1870-1873. doi: 10.4103/1673-5374.145342

21. Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008; 93(11 Suppl 1): S64-S73. doi: 10.1210/jc.2008-1613

22. Liu P, Li H, Cepeda J, et al. Regulation of inflammatory cytokine expression in pulmonary epithelial cells by pre-B-cell colonyenhancing factor via a nonenzymatic and AP-1-dependent mechanism. J Biol Chem. 2009; 284(40): 27344-27351. doi: 10.1074/jbc. M109.002519

23. Tilg H, Moschen AR. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6(10): 772-783. doi: 10.1038/nri1937

24. Lu LF, Yang SS, Wang CP, et al. Elevated visfatin/pre-B-cell colony-enhancing factor plasma concentration in ischemic stroke. J Stroke Cerebrovasc Dis. 2009; 18(5): 354-359. doi: 10.1016/j.jstrokecerebrovasdis.2009.01.003

25. Chen J, Weng JF, Hong WC, Luo LF, Yu W, Luo SD. Change in plasma visfatin level after severe traumatic brain injury. Peptides. 2012; 38(1): 8-12. doi: 10.1016/j.peptides.2012.08.016

26. Hallschmid M, Randeva H, Tan BK, Kern W, Lehnert H. Relationship between cerebrospinal fluid visfatin (PBEF/Nampt) levels and adiposity in humans. Diabetes. 2009; 58(3): 637-640. doi: 10.2337/db08-1176

27. Adams JD, Jr. Alzheimer’s disease, ceramide, visfatin and NAD. CNS Neurol Disord Drug Targets. 2008; 7(6): 492-498. Website. http://www.ingentaconnect.com/content/ben/cnsnddt/2008/00000007/00000006/art00001. Accessed April 3, 2017.


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