Serum aşikar hipotiroidizmin adipöz dokuda etkileri ve serum betatrophin düzeyleri

Öz

Amaç: Angiopoietin like peptit-8 olarak da bilinen betatrofin, adipöz doku ve karaciğerden sentezlenen glikoprotein yapısında bir adipokindir. Betatrofin, plazma lipoproteinlerinin hidrolizinde anahtar enzim olan lipoprotein lipaz’ı inhibe ederek yağ ve enerji metabolizmasında rol oynar. Tiroid hormonları enerji metabolizmasında aktif rol almasına rağmen kolesterol ve lipid metabolizmasıyla ilişkisi net değildir. Yaptığımız çalışmada hipotiroidi tanılı hastalarda serum betatrofin düzeylerinin enerji ve lipid metabolizması ile ilişkisini incelemeyi amaçladık.

Yöntemler: Bu bir vaka kontrol çalışmasıdır. Çalışmaya katılan hipotiroidi tanılı 44 hastanın (20 erkek, 24 kadın) yaş ortalaması 44,7 (13,8) idi. 19 Erkek ve 21 kadın olmak üzere toplam 40 sağlıklı gönüllü de kontrol grubu olarak çalışmaya katıldı. Sağlıklı gönüllülerin yaş ortalaması: 44,6 (14,4) yıl idi. Her iki grupta da açlık kan şekeri, AST, ALT, üre, kreatinin, TSH, serbest T3, serbest T4, HDL-kolesterol, LDL-kolesterol, trigliserit (TG), total kolesterol, anti-TPO, anti-TG, insülin, HOMA-IR düzeyleri ve ELISA yöntemiyle serum betatrofin düzeyleri ölçüldü. 

Bulgular: Kontrol grubuna kıyasla hipotiroidi tanısı konan hastalarda serum betatrofin düzeyleri anlamlı derecede yüksekti. (P=0,001). Serum betatrofin düzeyleri ile TSH, TG ve total kolesterol arasında pozitif yönde; HDL, serbest T3 ve serbest T4 ile negatif yönde korelasyon vardı. Hipotiroidili hasta grubunda anti-TPO yüksekliğine göre yapılan karşılaştırmada anlamlı farklılık yoktu (P=0,78).

Sonuç: Çalışmamızda hipotiroidi hastalarında serum betatrofin düzeylerinin yüksek olduğunu bulduk. Bu çalışma, klinik uygulamada betatrofeni hedef alan tedavilerin geliştirilmesinde faydalı olabilir.

Anahtar Kelimeler

• Hipotiroidizm,Betatrofin,Lipoprotein lipaz

The effects of overt hypothyroidism on adipose tissue and serum betatrophin levels

Öz

Aim: Betatrophin, also known as angiopoietin-like peptide-8, is an adipokine in glycoprotein structure synthesized from adipose tissue and liver. Betatrophin plays a role in fat and energy metabolism by inhibiting lipoprotein lipase, the key enzyme in the hydrolysis of plasma lipoproteins. Although thyroid hormones have an active role in energy metabolism, their relationship with cholesterol and lipid metabolism is not clear. In our study, we aimed to investigate the relationship of serum betatrophin levels with energy and lipid metabolism in patients with overt hypothyroidism.

Methods: This is a case-control study. The mean age of 44 patients (20 males, 24 females) with hypothyroidism was 44.7 (13.8). A total of 40 healthy volunteers, including 19 males and 21 females, were included in the study as a control group. The mean age of healthy volunteers was 44.6 (14.4) years. Fasting blood glucose, AST, ALT, urea, creatinine, TSH, free T3, free T4, HDL-cholesterol, LDL-cholesterol, triglyceride (TG), total cholesterol, anti-TPO, anti-TG, insulin, HOMA-IR levels and serum betatrophin levels were measured by ELISA and compared in both groups.

Results: Serum betatrophin levels were significantly higher in patients diagnosed with hypothyroidism compared to the control group (P=0.001). Serum betatrophin levels were positively correlated with TSH, TG and total cholesterol, and negatively correlated with HDL, free T3 and free T4 levels. There was no significant difference in the comparison of patients regarding anti-TPO levels in the hypothyroidism group (P=0.78).

Conclusion: In our study, we found that serum betatrophin levels were high in hypothyroid patients. This study may be useful in the development of treatments targeting betatrophin in clinical practice.

Anahtar Kelimeler

• Hypothyroidism,Betatrophin,Lipoprotein lipase

Kaynakça

1. 1. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappa B signaling through a c-AMP-dependent pathway. Circulation. 2000;102(11):1296-301.
2. 2. Krotkiewski M. Thyroid hormones in the pathogenesis and treatment of obesity. Eur J Pharmacol. 2002;440(2-3):85-98.
3. 3. Potenza M, Via MA, Yanagisawa RT. Excess thyroid hormone and carbohydrate metabolism. Endocr Pract. 2009;15(3):254-62.
4. 4. Bell A, Gagnon A, Grunder L, Parikh SJ, Smith TJ, Sorisky A. Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts. Am J Physiol Cell Physiol. 2000;279(2):335-40.
5. 5. Gierach M, Gierach J, Junik R. Insulin resistance and thyroid disorders. Endocrinol Pol. 2014;65(1):70-6.
6. 6. Seven R. Thyroid status and leptin in Basedow-Graves and multinodular goiter patients. J Toxicol Environ Health. 2001;63(8):575–81.
7. 7. Zimmermann-Belsing T, Brabant G, Holst JJ, Feldt-Rasmussen U. Circulating leptin and thyroid dysfunction. European Jour of Endocrinol. 2003;149(4):257-71.
8. 8. Abu-Farha M, Abubaker J, Al-Khairi I, Cherian P, Noronha F, Kavalakatt S, et al. Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome. Cardiovasc Diabetol. 2016;5:15-25.

9. 9. Santaniemi M, Ukkola O, Malo E, Bloigu R, Kesaniemi YA. Metabolic syndrome in the prediction of cardiovascular events: the potential additive role of hsCRP and adiponectin. Eur J Prev Cardiol. 2014;21(10):1242-8.
10. 10. Zhang R, Zhou SJ, Li CJ, Wang XN, Tang YZ, Chen R, et al. C-reactive protein/oxidised low-density lipoprotein/beta2-glycoprotein I complex promotes atherosclerosis in diabetic BALB/c mice via p38mitogen-activated protein kinase signal pathway. Lipids Health Dis. 2013;26:12-42.
11. 11. Wang J, Feng MJ, Zhang R, Yu DM, Zhou SJ, Chen R, et al. C-reactive protein/oxidized low density lipoprotein/beta 2 glycoprotein i complexes induce lipid accumulation and inflammatory reaction in macrophages via p38/mitogen activated protein kinase and nuclear factor kappa B signaling pathways. Mol Med Rep. 2016;14(4):3490-8.
12. 12. Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, et al. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation, Mol. Cell. Biol. 2000;20(14):5343–9.
13. 13. Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, et al. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisomeproliferator-activated receptor target gene, J. Biol. Chem. 2000;275(37):28488-93.
14. 14. Altun Ö, Dikker O, Arman Y, Ugurlukisi B, Kutlu O, Ozgun Cil E, et al. Serum Angiopoietin-like peptide 4 levels in patients with hepatic steatosis. Cytokine. 2018;111:496-9.
15. 15. Zhang R, Abou-Samra AB. Emerging roles of lipasin as a critical lipid regulator. Biochem Biophys Res Commun. 2013;432(3):401-5.
16. 16. Menon VU, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population. Jour Indian Med Assoc. 2009;107(2):72-7.
17. 17. Pucci E, Chiovato L, Pinchera A. Thyroid and lipid metabolism. Int J Obesity Rel Metab Dis. 2000;24(2):109-12.
18. 18. Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL, et al. Role of Adipokines in Cardiovascular Disease. Circ J. 2017;81(7):920-8.
19. 19. Ahirwar AK, Singh A, Jain A, Patra SK, Goswami B, Bhatnagar MK, et al. Role of Subclinical Hypothyroidism in Association with Adiponectin Levels Causing Insulin Resistance in Metabolic Syndrome: A Case Control Study. Tokai J Exp Clin Med. 2017;42(2):96-103.
20. 20. Hendrani AD, Adesiyun T, Quispe R, Jones SR, Stone NJ, Blumenthal RS, et al. Dyslipidemia management in primary prevention of cardiovascular disease: Current guidelines and strategies. World J Cardiol. 2016;8(2):201-10.
21. 21. Akbaba G, Berker D, Isık S, Tuna MM, Koparal S, Vural M, et al. Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients. Wien Klin Wochenschr. 2016;128(15-16):579-85.
22. 22. Stirrups KE, Masca NG, Erdmann J, Ferrario PG, Konig IR, Weeke PE, et al. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med. 2016;374(12):1134-44.
23. 23. Zhang R. The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking. Open Biol. 2016;6(4):150272.
24. 24. Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012;109(48):19751-6.
25. 25. Wang H, Eckel RH. Lipoprotein lipase: from gene to obesity, Am. J. Physiol. Endocrinol. Metab. 2009;297(2):e271-88.
26. 26. Goldberg IJ, Merkel M. Lipoprotein lipase: physiology, biochemistry, and molecular biology, Front. Biosci. 2001;6:388-405.
27. 27. Han C, Xia X, Liu A, Zhang X, Zhou M, Xiong C, et al. Circulating betatrophin is Increased in patients with overt and subclinical hypothyroidism. Biomed Res Int. 2016;2016:5090852.
28. 28. Luo M, Peng D. ANGPTL8: An Important Regulator in Metabolic Disorders. Front Endocrinol (Lausanne). 2018;9:169.