Effect of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: An Exploratory Metabolomics and Validation Study.
Li M., Wang X., Zeng N., Wu Z., Yu C., Sun D., Liu Y., Cao D., Zhang P., Yang L., Chen Y., Chen Z., Li L., Zhang Z., Lv J., Pang Y.
BACKGROUND: Bariatric surgery presents a significant alleviation for non-alcoholic fatty liver disease (NAFLD), which relies in part on achieving substantial weight loss in post-surgical period. We aimed to understand the effect of bariatric surgery on NAFLD remission via metabolomics and to validate the results in a general population-based cohort. METHODS: In a pilot study, ten patients with NAFLD who underwent bariatric surgery were enrolled. The remission of hepatic steatosis was assessed by MRI-derived proton density fat fraction (PDFF) before and 3-month after surgery. Temporal associations of body mass index (BMI) reduction, alteration in metabolomic biomarkers, and NAFLD remission were quantified by using cross-lagged models, which were then validated in a general population-based cohort (n = 1258). RESULTS: At 3-month after surgery, BMI reduction of 6.9 (SD 1.9) kg/m2 and MRI-PDFF reduction of 9.6% (5.4) (all p-value < 0.001) were achieved. Of the 64 metabolomic biomarkers quantified, 19 biomarkers showed significant differences between pre- and post-surgery (false discovery rate-corrected p-value < 0.05). Temporal associations were observed between BMI reduction and 5 metabolomic biomarkers, while 3 (chenodeoxycholic acid [CDCA], palmitoylcarnitine, and hippuric acid) were further validated in the general population-based cohort. CDCA was able to explain 18% of the association between BMI reduction and NAFLD remission (p-value < 0.05). In the general population-based cohort, Mendelian randomization showed that genetically elevated CDCA level was associated with a higher risk of liver fibrosis. CONCLUSIONS: CDCA is a potential mediator and may predict long-term surgical benefits in liver fibrosis regression.