Ciliary Neurotrophic Factor is Increased in the Plasma of Patients with Obesity and Its Levels Correlate with Diabetes and Inflammation Indices

Overview

Journal Sci Rep

Specialty Science

Date 2022 May 18

PMID 35585213

Authors

Jessica Perugini

Eleonora Di Mercurio

Angelica Giuliani

Jacopo Sabbatinelli

Anna Rita Bonfigli

Elena Tortato

Ilenia Severi

Saverio Cinti

Fabiola Olivieri

Carel W le Roux

Rosaria Gesuita

Antonio Giordano

Affiliations

Soon will be listed here.

Abstract

To establish whether obesity involves activation of endogenous ciliary neurotrophic factor (CNTF) signalling, we evaluated its plasma levels in patients with obesity and correlated its values with the major clinical and haematological indices of obesity, insulin resistance and systemic inflammation. This study involved 118 subjects: 39 healthy controls (19 men), 39 subjects with obesity (19 men) and 40 subjects with obesity and diabetes (20 men). Plasma CNTF and CNTF receptor α (CNTFRα) were measured using commercial ELISA kits. The results showed that plasma CNTF was significantly higher in males and females with obesity with and without diabetes than in healthy subjects. Women consistently exhibited higher levels of circulating CNTF. In both genders, CNTF levels correlated significantly and positively with obesity (BMI, WHR, leptin), diabetes (fasting insulin, HOMA index and HbA1c) and inflammation (IL-6 and hsCRP) indices. Circulating CNTFRα and the CNTF/CNTFRα molar ratio tended to be higher in the patient groups than in controls. In conclusion, endogenous CNTF signalling is activated in human obesity and may help counteract some adverse effects of obesity. Studies involving a higher number of selected patients may reveal circulating CNTF and/or CNTFRα as potential novel diagnostic and/or prognostic markers of obesity, diabetes and associated diseases.

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References

Rezende L, Santos G, Santos-Silva J, Carneiro E, Boschero A . Ciliary neurotrophic factor (CNTF) protects non-obese Swiss mice against type 2 diabetes by increasing beta cell mass and reducing insulin clearance. Diabetologia. 2012; 55(5):1495-504. DOI: 10.1007/s00125-012-2493-5. View

Van Dyken P, Lacoste B . Impact of Metabolic Syndrome on Neuroinflammation and the Blood-Brain Barrier. Front Neurosci. 2019; 12:930. PMC: 6297847. DOI: 10.3389/fnins.2018.00930. View

Adler R, Landa K, Manthorpe M, Varon S . Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science. 1979; 204(4400):1434-6. DOI: 10.1126/science.451576. View

LAMBERT P, Anderson K, Sleeman M, Wong V, Tan J, Hijarunguru A . Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. Proc Natl Acad Sci U S A. 2001; 98(8):4652-7. PMC: 31889. DOI: 10.1073/pnas.061034298. View

ODell S, Syddall H, Sayer A, Cooper C, Fall C, Dennison E . Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males. Eur J Hum Genet. 2002; 10(11):749-52. DOI: 10.1038/sj.ejhg.5200873. View

Stockli K, Lottspeich F, Sendtner M, Masiakowski P, Carroll P, Gotz R . Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature. 1989; 342(6252):920-3. DOI: 10.1038/342920a0. View

Crowe S, Turpin S, Ke F, Kemp B, Watt M . Metabolic remodeling in adipocytes promotes ciliary neurotrophic factor-mediated fat loss in obesity. Endocrinology. 2008; 149(5):2546-56. DOI: 10.1210/en.2007-1447. View

McGregor N, Poulton I, Walker E, Pompolo S, Quinn J, Martin T . Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role in bone growth and remodeling. Calcif Tissue Int. 2010; 86(3):261-70. DOI: 10.1007/s00223-010-9337-4. View

Watt J, Bone S, Pressler M, Cranston H, Paden C . Ciliary neurotrophic factor is expressed in the magnocellular neurosecretory system of the rat in vivo: evidence for injury- and activity-induced upregulation. Exp Neurol. 2005; 197(1):206-14. DOI: 10.1016/j.expneurol.2005.09.009. View

10.

Guillet C, Fourcin M, Chevalier S, Pouplard A, Gascan H . ELISA detection of circulating levels of LIF, OSM, and CNTF in septic shock. Ann N Y Acad Sci. 1995; 762:407-9. DOI: 10.1111/j.1749-6632.1995.tb32349.x. View

11.

Shpak A, Guekht A, Druzhkova T, Rider F, Gudkova A, Gulyaeva N . Increased ciliary neurotrophic factor in blood serum and lacrimal fluid as a potential biomarkers of focal epilepsy. Neurol Sci. 2021; 43(1):493-498. DOI: 10.1007/s10072-021-05338-4. View

12.

Deverman B, Patterson P . Cytokines and CNS development. Neuron. 2009; 64(1):61-78. DOI: 10.1016/j.neuron.2009.09.002. View

13.

Perugini J, Di Mercurio E, Tossetta G, Severi I, Monaco F, Reguzzoni M . Biological Effects of Ciliary Neurotrophic Factor on hMADS Adipocytes. Front Endocrinol (Lausanne). 2019; 10:768. PMC: 6861295. DOI: 10.3389/fendo.2019.00768. View

14.

Severi I, Perugini J, Mondini E, Smorlesi A, Frontini A, Cinti S . Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus. Front Neurosci. 2014; 7:263. PMC: 3873503. DOI: 10.3389/fnins.2013.00263. View

15.

Kishida K, Funahashi T, Shimomura I . Adiponectin as a routine clinical biomarker. Best Pract Res Clin Endocrinol Metab. 2014; 28(1):119-30. DOI: 10.1016/j.beem.2013.08.006. View

16.

Ott V, Fasshauer M, Dalski A, Klein H, Klein J . Direct effects of ciliary neurotrophic factor on brown adipocytes: evidence for a role in peripheral regulation of energy homeostasis. J Endocrinol. 2002; 173(2):R1-8. DOI: 10.1677/joe.0.173r001. View

17.

Ichiyama T, Nishikawa M, Yoshitomi T, Matsubara T, Hayashi T, Furukawa S . Elevated cerebrospinal fluid level of ciliary neurotrophic factor in acute disseminated encephalomyelitis. J Neurol Sci. 2000; 177(2):146-9. DOI: 10.1016/s0022-510x(00)00366-x. View

18.

Saltiel A, Olefsky J . Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017; 127(1):1-4. PMC: 5199709. DOI: 10.1172/JCI92035. View

19.

. 2. Classification and Diagnosis of Diabetes: . Diabetes Care. 2019; 43(Suppl 1):S14-S31. DOI: 10.2337/dc20-S002. View

20.

Venema W, Severi I, Perugini J, Di Mercurio E, Mainardi M, Maffei M . Ciliary Neurotrophic Factor Acts on Distinctive Hypothalamic Arcuate Neurons and Promotes Leptin Entry Into and Action on the Mouse Hypothalamus. Front Cell Neurosci. 2020; 14:140. PMC: 7253709. DOI: 10.3389/fncel.2020.00140. View