Pediatr Gastroenterol Hepatol Nutr.  2018 Apr;21(2):111-117. 10.5223/pghn.2018.21.2.111.

Investigation of Blood Betatrophin Levels in Obese Children with Non-Alcoholic Fatty Liver Disease

• Battal F
• Türkön H
• Aylanç N
• Aylanç H
• Yıldırım S
• Kaymaz N
• Uysal S

• KMID: 2409362
• DOI: http://doi.org/10.5223/pghn.2018.21.2.111

Abstract

PURPOSE
The prevalence of obesity has significantly increased among children and adolescents worldwide and is becoming an important health care problem in parallel with the increased prevalence of obesity pediatric non-alcoholic fatty liver disease. Betatrophin is a newly define hormone that is commonly secreted by liver and plays role in glucose tolerance. This study aimed to investigate the relationship between serum betatrophin levels and non-alcoholic fatty liver disease in obese children.
METHODS
The study included 40 obese children with a body mass index (BMI) above 95th centile, and 35 non-obese subjects with a BMI 3-85th centile, whose age and gender were similar to those of the patient group. For the evaluation of metabolic parameters fasting serum glucose, insulin, alanine aminotransferase, aspartate aminotransferase, lipid profile and serum betatrophin levels were measured. Total cholesterol: high-density lipoprotein cholesterol and low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratios were calculated as "atherogenic indices."
RESULTS
Serum betatrophin levels of the obese subjects were similar to that of non-obese subjects (p=0.90). Betatrophin levels were not correlated with the metabolic parameters.
CONCLUSION
In the present study, levels of betatrophin are not different between obese and insulin resistant children and non-obese subjects, and they are not correlated with atherogenic indices. To elucidate the exact role of betatrophin in obesity, further studies are required to identify the betatrophin receptor and/or other possible cofactors.

Keyword

Betatrophin; Child; Obesity; Liver

MeSH Terms

Adolescent
Alanine Transaminase
Aspartate Aminotransferases
Blood Glucose
Body Mass Index
Child*
Cholesterol
Delivery of Health Care
Fasting
Glucose
Humans
Insulin
Lipoproteins
Liver
Non-alcoholic Fatty Liver Disease*
Obesity
Prevalence
Alanine Transaminase
Aspartate Aminotransferases
Cholesterol
Glucose
Insulin
Lipoproteins

Figure

• 

  Fig. 1 Comparison of serum betatrophin concentration between obese and non-obese subjects.

Reference

1. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006; 118:1388–1393.

2. Takahashi Y, Fukusato T. Pediatric nonalcoholic fatty liver disease: overview with emphasis on histology. World J Gastroenterol. 2010; 16:5280–5285.

3. Wong RJ, Ahmed A. Obesity and non-alcoholic fatty liver disease: disparate associations among Asian populations. World J Hepatol. 2014; 6:263–273.

4. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci. 1995; 40:2002–2009.

5. Liu L, Mei M, Yang S, Li Q. Roles of chronic low-grade inflammation in the development of ectopic fat deposition. Mediators Inflamm. 2014; DOI: 10.1155/2014/418185.

6. Nguyen P, Leray V, Diez M, Serisier S, Le Bloc'h J, Siliart B, et al. Liver lipid metabolism. J Anim Physiol Anim Nutr (Berl). 2008; 92:272–283.

7. Marzuillo P, Del Giudice EM, Santoro N. Pediatric non-alcoholic fatty liver disease: new insights and future directions. World J Hepatol. 2014; 6:217–225.

8. Dali-Youcef N, Mecili M, Ricci R, Andrès E. Metabolic inflammation: connecting obesity and insulin resistance. Ann Med. 2013; 45:242–253.

9. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest. 2003; 112:1785–1788.

10. Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep. 2014; 4:5013.

11. Gómez-Ambrosi J, Pascual E, Catalán V, Rodríguez A, Ramírez B, Silva C, et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014; 99:E2004–E2009.

12. Wang Y, Quagliarini F, Gusarova V, Gromada J, Valenzuela DM, Cohen JC, et al. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci U S A. 2013; 110:16109–16114.

13. Wu S, Gao H, Ma Y, Fu L, Zhang C, Luo X. Characterisation of betatrophin concentrations in childhood and adolescent obesity and insulin resistance. Pediatr Diabetes. 2016; 17:53–60.

14. Ozturk A, Mazicioglu MM, Hatipoglu N, Budak N, Keskin G, Yazlak Z, et al. Reference body mass index curves for Turkish children 6 to 18 years of age. J Pediatr Endocrinol Metab. 2008; 21:827–836.

15. Valerio G, Licenziati MR, Iannuzzi A, Franzese A, Siani P, Riccardi G, et al. Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy. Nutr Metab Cardiovasc Dis. 2006; 16:279–284.

16. Singh D, Das CJ, Baruah MP. Imaging of non alcoholic fatty liver disease: a road less travelled. Indian J Endocrinol Metab. 2013; 17:990–995.

17. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr. 2017; 64:319–334.

18. Fenzl A, Itariu BK, Kosi L, Fritzer-Szekeres M, Kautzky-Willer A, Stulnig TM, et al. Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals. Diabetologia. 2014; 57:1204–1208.

19. Hu H, Sun W, Yu S, Hong X, Qian W, Tang B, et al. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. Diabetes Care. 2014; 37:2718–2722.

20. Abu-Farha M, Abubaker J, Al-Khairi I, Cherian P, Noronha F, Hu FB, et al. Higher plasma betatrophin/ ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance. Sci Rep. 2015; 5:10949.

21. Calan M, Yilmaz O, Kume T, Unal Kocabas G, Yesil Senses P, Senses YM, et al. Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome. Endocrine. 2016; 53:271–279.

22. Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012; 424:786–792.

23. 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; 109:19751–19756.

24. Gao T, Jin K, Chen P, Jin H, Yang L, Xie X, et al. Circulating betatrophin correlates with triglycerides and postprandial glucose among different glucose tolerance statuses--a case-control study. PLoS One. 2015; 10:e0133640.

25. Chen X, Lu P, He W, Zhang J, Liu L, Yang Y, et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab. 2015; 100:E96–100.