Fibroblast growth factor-21 to adiponectin ratio: A potential biomarker to monitor liver fat in children with obesity

Authors: TAS, EMIR - University Arkansas For Medical Sciences (UAMS); BAI, SHASHA - University Arkansas For Medical Sciences (UAMS); OU, XIAWEI - Arkansas Children'S Nutrition Research Center (ACNC); MERCER, KELLY - University Arkansas For Medical Sciences (UAMS); LIN, HAIXIA - University Arkansas For Medical Sciences (UAMS); MANSFIELD, KORI - University Arkansas For Medical Sciences (UAMS); BUCHMANN, ROBERT - University Arkansas For Medical Sciences (UAMS); DIAZ, EVA - University Arkansas For Medical Sciences (UAMS); ODEN, JON - University Arkansas For Medical Sciences (UAMS); BORSHEIM, ELISABET - University Arkansas For Medical Sciences (UAMS); Ferruzzi, Mario; DRANOFF, JONATHAN - University Arkansas For Medical Sciences (UAMS)

Submitted to: Frontiers in Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2020
Publication Date: 9/17/2020
Citation: Tas, E., Bai, S., Ou, X., Mercer, K., Lin, H., Mansfield, K., Buchmann, R., Diaz, E.C., Oden, J., Borsheim, E., Adams, S.H., Dranoff, J. 2020. Fibroblast growth factor-21 to adiponectin ratio: A potential biomarker to monitor liver fat in children with obesity. Frontiers in Endocrinology. https://doi.org/10.3389/fendo.2020.00654.
DOI: https://doi.org/10.3389/fendo.2020.00654

Interpretive Summary: Children with obesity have a much higher risk of developing chronic liver diseases. One such problem is the non-alcoholic fatty liver disease, which is a condition in which too much fat builds up in the liver. More than one-third of obese children are estimated to have fatty liver disease. If not identified and treated promptly, this condition may worsen and lead to irreversible stages of liver disease characterized by inflammation and stiffening of the liver. Furthermore, prevention of fatty liver disease through nutrition and exercise is a high priority, but there is a need for tools to be able to identify at-risk individuals and to measure the impact of interventions and preventative measures. There is no simple test to diagnose a fatty liver disease or quantify the amount of fat built in the liver. Currently, standard blood tests have low reliability for the diagnosis and monitoring of disease activity or pre-disease risk. Liver biopsy is the best test for diagnosis and monitoring liver fat content over a period of time, but the risks of doing a biopsy need to be carefully assessed and weighed against the benefits. Besides, liver biopsy is expensive, and not available at every center. Thus, there is a big need for the development of simple tools, such as more accurate blood tests, to measure liver fat and to diagnose fatty liver disease in children, and to understand how fat content is changing in response to treatments or prevention strategies. In this study, we showed that measuring the levels of two different blood hormones, fibroblast growth factor-21 (FGF21) and adiponectin, can help determine how the liver fat content of a child is changing over time. This is particularly important because the course of the disease can be monitored, and treatment strategies can be individualized. It is also possible that measurement of such factors in the blood could identify at-risk individuals and thus those who would benefit most from nutritional and exercise improvements. Accurate quantification of liver fat content through easily available, cheap, and effective blood tests may eliminate the need for a costly and potentially dangerous liver biopsy for the diagnosis and monitoring of fatty liver disease in children. Given the high frequency of this condition in society, development of predictive tools such as a blood test will help in public health efforts to prevent disease and mitigate fatty liver disease progression in obese children.

Technical Abstract: There is a pressing need for effective and non-invasive biomarkers to track intrahepatic triglyceride (IHTG) in children at-risk for non-alcoholic fatty liver disease (NAFLD), as standard-of-care reference tools, liver biopsy and magnetic resonance imaging (MRI), are impractical to monitor the course disease. We aimed to examine the association between serum fibroblast growth factor (FGF)-21 to adiponectin ratio (FAR) and IHTG as assessed by MRI in children with obesity. Serum FGF21 and adiponectin levels and IHTG were measured at two time points (baseline, 6 months) in obese children enrolled in a clinical weight loss program. The association between percent change in FAR and IHTG at final visit was examined using a multiple linear regression model. At baseline, FAR was higher in the subjects with NAFLD (n = 23, 35.8 +/- 41.9 pg/ng) than without NAFLD (n = 35, 19.8 +/- 13.7 pg/ng; p = 0.042). Forty-eight subjects completed both visits and were divided into IHTG loss (>=1% reduction than baseline), no change (within +/- 1% change), and gain (>=1% increase than baseline) groups. At 6 months, the percent change in FAR was different among the three groups (p = 0.005). Multiple linear regression showed a positive relationship between percent change in FAR and the final liver fat percent in sex and pubertal stage-similar subjects with NAFLD at baseline (slope coefficient 6.18, 95% CI 1.90–10.47, P = 0.007), but not in those without NAFLD. Higher value in percent increase in FAR is positively associated with higher level of IHTG percent value at 6 months in children with baseline NAFLD. FAR could be a potential biomarker to monitor the changes in IHTG in children with NAFLD.