Effects of serum branched-chain amino acids on nonalcoholic fatty liver disease and subsequent cardiovascular disease

Background To reveal the role of branched-chain amino acids (BCAAs) in the development and progression of nonalcoholic fatty liver disease (NAFLD) and the effect on the incidence of subsequent cardiovascular disease. Methods A total of 1302 subjects in the cohort study of the Huai'an Diabetes Prevention Program were divided into two groups according to whether NAFLD was present at baseline. The group without NAFLD at baseline was only followed up, and the group with NAFLD at baseline received diet and exercise interventions. Anthropometric and biochemical examinations were performed at baseline and at the end of 4 years for all subjects. Serum BCAA (leucine, isoleucine, and valine) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometry. The associations of baseline serum BCAA levels with the risk for NAFLD, coronary heart disease (CHD), and cardiovascular events (CVEs) after 4 years were further evaluated. Results (1) At baseline and after the 4-year follow-up, baseline serum leucine, valine, and total BCAAs in the NAFLD group were significantly higher than those in the non-NAFLD group ( p < 0.05). (2) According to whether NAFLD was present at baseline and after follow-up, all subjects were divided into four groups, including the control group, new case group, improvement group, and unchanged group. There was no significant difference in baseline BCAAs levels between the new case group and the improvement group ( p > 0.05). (3) Risk factors for the occurrence and development of NAFLD were analysed by a multiple logistic regression model according to whether NAFLD existed at baseline. Serum leucine (OR = 1.058, 95% CI 1.005–1.114, p = 0.033) and total BCAAs (OR = 1.023, 95% CI 1.001–1.046, p = 0.045) were independent risk factors for new-onset NAFLD. Serum valine (OR = 1.131, 95% CI 1.043–1.226, p = 0.003), and total BCAAs (OR = 1.040, 95% CI 1.003–1.078, p = 0.035) were independent risk factors showing that NAFLD could not be reversed. (4) The cross-table Chi-square test showed that the incidence of both CHD and CVEs was significantly highest in the new case group ( p < 0.05). (5) After adjusting for confounding factors, baseline isoleucine, valine, and BCAA levels were independently associated with new-onset CHD in subjects with or without NAFLD at baseline ( p < 0.05). Conclusions High BCAA levels exacerbate the risk of CHD and CVEs by influencing the occurrence and progression of NAFLD. However, lifestyle interventions could reverse the risk of NAFLD, CHD and CVEs associated with BCAAs.