당대사기능 이상에 따른 이소성 지방과 혈중 fibroblast growth factor-21 농도의 연관성

Abstract

Ectopic fat accumulation is known to be correlated with many metabolic disorders like insulin resistance, obesity, cardiovascular disease, and diabetes. It has been studied that ectopic fat accumulation is associated with adiponectin and resistin. We wanted to investigate the association between ectopic fat and new metabolic regulators such as fibroblast growth factor-21 (FGF-21) and adipose triglycerol lipase (ATGL). Furthermore, we wanted to analyze whether these regulators are associated with glucose metabolism and/or coronary artery disease. Subjects who underwent multi-detector CT were enrolled in this study from Seoul National University Bundang Hospital. Pericardial fat volume, visceral fat area, intramyocellular fat (low density muscle area), and hepatic fat (liver-spleen Hounsfield units (HU) difference) were measured by a dedicated software program (Rapidia 2.8, Infinitt). Coronary artery stenosis and the plaque characteristics were measured. Plasma FGF-21, high molecular weight (HMW) adiponectin, and ATGL were measured from fasting plasma sample by ELISA. A total of 190 subjects were enrolled in the study. Plasma FGF-21 was significantly increased with pericardial fat volume in total subjects (r=0.190, p= 0.018). In subgroup analysis with T2DM, plasma FGF-21 showed a significant correlation with all ectopic fat; pericardial fat, r=0.336, p=0.004; visceral fat, r=0.240, p=0.046; low density muscle area/normal density muscle area, r=0.282, p=0.017; liver-spleen HU difference, r=-0.308, p=0.028. Plasma HMW adiponectin level was positively correlated to subcutaneous fat (p<0.05) but was not correlated with ectopic fat accumulation. There were 48 (25%) normal glucose tolerance (NGT), 53 (28%) prediabetes, and 89 (47%) type 2 diabetes (T2DM). Ectopic fat accumulation was higher in T2DM and prediabetes than NGT (pericardial, visceral, intramyocellular fat; p<0.05, hepatic fat; p=0.059). All ectopic fat were significantly associated with HOMA-IR (p<0.001). Pericardial fat and visceral fat were significantly associated with insulin resistance independently of age and BMI (p<0.05). Coronary artery disease was associated with plasma HMW adiponectin after adjusting for age, BMI and diabetes, but there were no associations with other plasma markers. T2DM had significantly higher plasma levels of FGF-21 and lower levels of HMW adiponectin than NGT (p<0.05). Plasma levels of ATGL were not significantly different (p=0.185). Pericardial fat and intramyocellular fat were significantly associated with coronary artery stenosis and calcium score (p<0.05). In conclusion, plasma FGF-21 level correlated positively with ectopic fat as well as glucose level. These results indicate that FGF-21 could be a useful biomarker predicting ectopic fat accumulations.