Lipid metabolism, BMI and the risk of nonalcoholic fatty liver disease in the general population: evidence from a mediation analysis

Abstract

Background: Body mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD.

Method: Using data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation.

Result: After fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (All P-value < 0.001). Mediation analysis showed that both traditional and non-traditional lipid parameters mediated the association between BMI and NAFLD (All P-value of proportion mediate < 0.001), among which non-traditional lipid parameters such as RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio accounted for a relatively large proportion, 11.4%, 10.8%, 10.2%, and 10.2%, respectively. Further stratified analysis according to sex, age, and BMI showed that this mediation effect only existed in normal-weight (18.5 kg/m² ≤ BMI < 25 kg/m²) people and young and middle-aged (30-59 years old) people; moreover, the mediation effects of all lipid parameters except TC accounted for a higher proportion in women than in men.

Conclusion: The new findings of this study showed that all lipid parameters were involved in and mediated the risk of BMI-related NAFLD, and the contribution of non-traditional lipid parameters to the mediation effect of this association was higher than that of traditional lipid parameters, especially RC, RC/HDL-C ratio, non-HDL-C/HDL-C ratio, and TC/HDL-C ratio. Based on these results, we suggest that we should focus on monitoring non-traditional lipid parameters, especially RC and RC/HDL-C ratio, when BMI intervention is needed in the process of preventing or treating NAFLD.

Keywords: BMI; Mediation analysis; NAFLD; Non-traditional lipid parameter; Remnant cholesterol.