The effect of liver enzymes on body composition: A Mendelian randomization study

Abstract

BackgroundHigher alanine transaminase (ALT), indicating poor liver function, is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function affects muscle mass. To clarify, we assessed the associations of liver enzymes with muscle and fat mass observationally with two-sample MR as a validation. MethodsIn the population-representative "Children of 1997" birth cohort (n = 3,455), we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) at~17.5 years with muscle mass and body fat percentage observationally. Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) were applied to fat-free and fat mass in the UK Biobank (n =~331,000) to obtain unconfounded MR estimates. ResultsObservationally, ALT was positively associated with muscle mass (0.11 kg per IU/L, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15% per IU/L, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03 kg per IU/L, 95% CI -0.04 to -0.02) and fat percentage (-0.02% per IU/L, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41 kg per 100% in concentration, 95% CI -0.64 to -0.19) and fat mass (-0.58 kg per 100% in concentration, 95% CI -0.85 to -0.30). ALP and GGT were unclearly associated with fat-free mass or fat mass. GM, et al. (2020) The effect of liver enzymes on body composition: A Mendelian randomization study. PLoS ONE 15(2): e0228737. ConclusionALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes and suggests a potential target of intervention.Liver enzymes on body composition PLOS ONE | https://doi.org/10.

Analysis of the relationship between serum alanine aminotransferase and body composition in Chinese women

“…Alanine aminotransferase is an enzyme that is located primarily in the cytosol of hepatocytes, and thus, it is a specific marker for liver injury 10 . Many studies have confirmed the association between ALT and body composition 6,11 . However, some research has found no association between serum ALT and fat mass in women, 6 and the relationship between ALT and the body composition of postmenopausal women in China has not been reported, to date.…”

“…10 Many studies have confirmed the association between ALT and body composition. 6,11 However, some research has found no association between serum ALT and fat mass in women, 6 and the relationship between ALT and the body composition of postmenopausal women in China has not been reported, to date. The current study found that ALT was positively associated with the fat mass index in this sample.…”