Non-alcoholic Fatty Liver Disease and Its Association with Serum Nesfatin- 1

Year 2021, , 45 - 53, 30.01.2021

Talat Ayyıldız , Enver Dolar Barbaros Oral , Şener Arıkan Saduman Balaban

https://doi.org/10.21673/anadoluklin.824294

Abstract

Aim: Nesfatin -1 is a novel peptide which is defined as satiety peptide with an anorexigenic action. Studies have shown its association with metabolic syndrome and insulin resistance. With this study, we sought to establish the association between clinicopathologic characteristics of patients with biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) and Nesfatin-1.

Materials and Methods: Serum Nesfatin-1 levels were measured using the enzyme-linked immunosorbent assay in 59 patients with histologically diagnosed NAFLD and a control group comprising 32 healthy subjects.

Results: Serum Nesfatin-1 level did not significantly differ between patients with NAFLD and control group (p<0.170). Simple correlation analysis showed that nesfatin-1 levels decreased as body mass index increased (p=0.043) and nesfatin-1 values increased in proportion to elevations in AST (p=0.05). A multiple regression model constructed for assessment showed that while portal inflammation (B=10.767, p=0.007), body mass index score (B=-0.510, p<0.001) and HDL cholesterol (B=-0.208, p<0.001) had a negative association with nesfatin-1, age (B=0.120, p=0.031), sex (lower levels among males versus females) (B=-40.897, p<0.001), systolic blood pressure (B=0.063, P=0.050) and AST (B=0.033, p=0.019) had a positive and linear significant association with nesfatin-1.

Conclusion: In conclusion, the findings point out that serum nesfatin-1 level may be an independent predictor of portal inflammation in NAFLD.

Keywords

NAFLD, ; nesfatin-1, portal inflammation, fibrosis, obesity

Non-Alkolik Yağlı Karaciğer Hastalığı Ve Serum Nesfatin-1 İlişkisi

Abstract

Amaç: Nesfatin -1 anoreksijenik etkisi olan tokluk peptidi olarak tanımlanan yeni bir peptittir. Yapılan çalışmalarda metabolik sendrom ve insülin rezistansı ile ilişkisi olduğu ortaya konmuştur. Biz bu çalışma ile biyopsi tanılı non-alkolik yağlı karaciğer hastalığı (NAFLD) olan hastaların klinikopatolojik özellikleri ile Nesfatin-1 arasındaki ilşikiyi ortaya koymaya çalıştık.

Gereç ve Yöntemler: Histolojik olarak non-alkolik yağlı karaciğer hastalığı tanısı konmuş 59 hasta ve 32 sağlıklı kontrol grubunda serum Nesfatin-1 seviyeleri enzyme-linked immunosorbent assay (ELISA) yöntemiyle ölçülmüştür.

Bulgular: Serum Nesfatin-1 seviyesi non-alkolik yağlı karaciğer hastalığı olanlarla kontrol grubu arasında anlamlı farklılık göstermiyordu (p<0,170). Basit korelasyon analizinde vücut kitle indeks (VKİ) arttıkça nesfatin-1 seviyelerinin azaldığı (p=0.043) ve AST arttıkça nesfatin-1 değerlerinin de arttığı (p=0,05) görüldü. Çoklu regresyon modeli oluşturularak yapılan incelemede ise portal inflamasyon (B=10,767, p=0,007), VKİ skoru (B=-0,510, p<0,001) ve HDL kolesterol (B=-0,208, p<0,001) ile nesfatin-1 arasında negatif yönlü ilişki yaş (B=0,120, p=0,031), cinsiyet (erkeklerde kadınlara göre daha düşük) (B=-40,897, p<0,001) sistolik kan basıncı (B=0,063, P=0,050) ve aspartat aminotransferaz (B=0,033, p=0,019) arasında pozitif ve doğrusal anlamlı ilişki bulunmuştur.

Sonuçlar: Özet olarak bulgular serum nesfatin-1 seviyesinin non-alkolik yağlı karaciğer hastalığında portal inflamasyonun bağımsız bir prediktörü olabileceğine işaret etmektedir.

Keywords

Non-alkolik yağlı karaciğer hastalığı, nesfatin-1, portal inflamasyon, fibrozis, obezite

References

• Chitturi S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD. Asia-Pacific Working Party on NAFLD . Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol. 2007;22(6):778-87.
• Younossi ZM, Marchesini G, Pinto-Cortez H, Petta S. Epidemiology of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Implications for liver transplantation. Transplantation. 2019;103(1):22-27.
• Byrne CD, Olufadi R, Bruce KD, Cagampang FR, Ahmed MH. Metabolic disturbances in non-alcoholic fatty liver disease. Clin Sci (Lond). 2009;116(7):539–64.
• Sanyal AJ. Past, present and future perspectives in non-alcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2019;16(6):377-86.
• Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Non-alcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120(5):1183-92.
• Marchisello S, Di Pino A, Scicali R, Urbano F, Piro S, Purrello F, et al. Pathophysiological, molecular and therapeutic issues of non-alcoholic fatty liver disease: An overview. Int J Mol Sci. 2019;20(8).pii:E1948.
• Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443(7112):709–12.
• Brailoiu GC, Dun SL, Brailoiu E, Inan S, Yang J, Chang JK. Nesfatin-1:distribution and interaction with a G protein-coupled receptor in the rat brain. Endocrinology. 2007;148(10):5088–94.
• Kohno D, Nakata M, Maejima Y, Shimizu H, Sedbazar U, Yoshida N, et al. Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding. Endocrinology. 2008;149(3):1295–301.
• Su Y, Zhang J, Tang Y, Bi F, Liu JN. The novel function of nesfatin-1: antihyperglycemia. Biochem Biophys Res Commun. 2010;391(1):1039–42.
• American Diabetes Association: expert committee on the diagnosis and classification of diabetes mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20(7):1183–97.
• National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97.
• Levy JC, Matthews DR, Herman MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21(12):2191-92.
• Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, et al. Endpoints and clinical trial design for non-alcoholic steatohepatitis. Hepatology. 2011;54(1):344–53.
• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for non-alcoholic fatty liver disease. Hepatology. 2005; 41(6): 1313–21.
• Gonzalez R, Tiwari A, Unniappan S. Pancreatic beta cells colocalize insulin and pronesfatin immunoreactivity in rodents. Biochem Biophys Res Commun. 2009;381(4):643–8.
• Li QC, Wang HY, Chen X, Guan HZ, Jiang ZY. Fasting plasma levels of nesfatin-1 in patients with type 1 and type 2 diabetes mellitus and the nutrient-related fluctuation of nesfatin-1 level in normal humans. Regul Pept. 2010;159(1-3):72–7.
• Başar O, Akbal E, Köklü S, Koçak E, Tuna Y, Ekiz F, et al. A novel appetite peptide, nesfatin-1 in patients with non-alcoholic fatty liver disease. Scand J Clin Lab Invest. 2012;72(6):479-83.
• Atsuchi K, Asakawa A, Ushikai M, Ataka K, Tsai M, Koyama K, et al. Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice. Neuroreport. 2010;21(15):1008-11.
• Shimizu H, Oh-I S, Okada S, Mori M. Nesfatin-1: an overview and future clinical application. Endocr J. 2009;56(4):537–43.
• Tsuchiya T, Shimizu H, Yamada M, Osaki A, Oh-I S, Ariyama Y, et al. Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in nonobese males. Clin Endocrinol (Oxf) . 2010;73(4):484-90.
• Yosten GL, Samson WK. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009;297(2):330-6.
• Yamawaki H, Takahashi M, Mukohda M, Morita T, Okada M, Hara Y. A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats. Biochem. Biophys. Res. Commun 2012;418(4):676–81.
• Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, et al. Portal chronic inflammation in non-alcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-clinicopathologic correlations from the non-alcoholic steatohepatitis clinical research network. Hepatology. 2009;49(3):809–20.
• Iwata T, Arai K, Saito N, Murata K. The association between dietary lifestyles and hepatocellular injury in Japanese workers. Tohoku J Exp Med. 2013;231(4):257-63.
• Finelli C, Tarantino G. Have guidelines addressing physical activity been established in non-alcoholic fatty liver disease?. World J Gastroenterol. 2012;18(46):6790-800.