The global prevalence of NAFLD has been increasing over the past two decades, parallel to the rising prevalence of obesity . Previous studies have shown liver regulates energy homeostasis through hepatokine secretion . Moreover, hepatokine secretion is generally improved after bariatric surgery, which might drive the long-term metabolic improvements following bariatric surgery . Recently, studies found that plasma FGL-1 levels are associated with obesity . However, the role of FGL-1 in patients with obesity who undergo LSG remains obscure, and purpose of the present study is to investigate the changes of FGL-1 after LSG, and whether it is correlated with other metabolic indices.
In the present study, patients with obesity have higher levels of FGL-1 than individuals with normal weight. In addition, linear regression analysis showed that FGL-1 levels were positively correlated with BMI, SBP, DBP, ALT, AST, γGT, TG, FPG, FINS, HOMA-IR, UA, and were negatively correlated with HDL. These results are consistent with previous cross-sectional studies that FGL-1 is associated with body weight, blood pressure, lipid metabolism, insulin resistance and uric acid [25, 26]. One of the mechanisms behind this may be that FGL-1 induces hepatic lipid accumulation by activating ERK1/2 pathway . Moreover, FGL-1 promotes adipogenesis through an ERK1/2-C/EBPβ-dependent pathway . In addition, increased FGL-1 expression induces insulin resistance through an EGFR/JNK mediated pathway . Since FGL-1 is not only associated with obesity, but also with other obesity-related indicators. Thus, it is interesting to explore the changes of FGL-1 after LSG and the clinical indicators related to the changes.
With the decrease in body weight, FGL-1 levels significantly decreased at 6 months after LSG. Our study is the first to show a significant reduction in elevated levels of FGL-1 after weight loss, which suggested LSG can reduce FGL-1 levels. In previous studies, Wu et al. indicated that deletion of FGL-1 decreased oleic acid-induced lipid accumulation in HepG2 cells and knockdown of FGL-1 in adipose tissue of mice decreased adipose hypertrophy [15, 18], which suggested reduced FGL-1 after LSG may be related to the reduction of lipid accumulation and adipose hypertrophy. However, the changes in FGL-1 were not associated with the changes in BMI (r = -0.035, p = 0.791, data not shown). The same result as ours, Lim et al. found bariatric surgery might alter hepatokines levels independent of weight loss .
After adjusting for possible confounders, the changes in FGL-1 are associated with the improvement of ALT and AST levels, which was supported by the previous clinical studies showing that changes in hepatokines levels were related to improvement of hepatic metabolism after bariatric surgery . Moreover, in previous experiments with rats, compared with the SHAM surgery group, the expression of FGF-21 mRNA in the liver of the bariatric surgery group was lower, suggesting that the expression of the hepatokine in the liver was changed and the liver metabolic functions were improved after bariatric surgery . To our knowledge, FGL-1 is known to regulate hepatocyte proliferation and is expressed mainly in the liver [28, 29]. Meanwhile, it has been reported that plasma FGL-1 concentrations increased significantly in hyperglycemic crisis patients and decreased significantly after treatment with improved liver function . Since circulating ALT and AST can be associated with the progression of chronic liver disease , postoperative improvement of FGL-1 levels is closely related to liver function. Besides, many studies have shown that NAFLD can be improved after bariatric surgery, but there was no correlation could be detected between the improvement of NAFLD and weight loss . There seems to be some mechanism for improving liver function independent of weight loss that needs to be explored in future studies.
Meanwhile, the changes in FGL-1 are associated with the improvement of UA levels after adjusting for possible confounders. Additionally, another study found that with increasing FGL-1 tertiles, patients had higher UA levels . UA is produced in the liver, adipose tissue and muscle . After excessive consumption of fructose and sucrose, the liver will decrease the peripheral availability of anabolic factors such as hormones and amino acids, and produce catabolic effectors such as hepatokines and UA . On the other hand, Xie et al. found UA induces hepatic fat accumulation via the ROS/JNK/AP-1 pathway . Therefore, UA is closely related to liver metabolism which may explain the association between UA and FGL-1. However, the causal relationship between UA and FGL-1 needs to be further verified by experiments.
Our study is the first study to follow up on the change in FGL-1 levels before and after bariatric surgery, and our results showed losing weight can significantly reduce FGL-1 levels. Besides, these results demonstrated LSG can reduce FGL-1 levels which may be involved in the mechanism of improving liver function and uric acid metabolism, but not body weight and glucolipid metabolism. However, this study has several limitations. Firstly, our study lacked the results of detecting NAFLD. Secondly, this was a single-center retrospective study only included Chinese individuals and has a relatively small sample size. Finally, there was a short follow-up duration of this study. Therefore, future research is needed to use a larger sample size and longer follow-up duration to verify the results of this study.