Circulating osteocalcin concentrations are associated with parameters of liver fat infiltration and increase in parallel to decreased liver enzymes after weight loss.

Abstract

The expression of liver genes was associated with insulin action in osteocalcin knockout mice. Our findings suggest that osteocalcin may play a role in the development of insulin resistance-associated fatty liver disease. The expression of insulin target genes was decreased in the liver of mice lacking osteocalcin. We aimed to explore the association of liver enzymes with osteocalcin. The associations were evaluated in a cross-sectional study (266 men) and following weight loss in 28 obese subjects (nine male, 19 females). In the cross-sectional study, circulating osteocalcin concentration was negatively associated with alanine transaminase (ALT) (p = 0.002) and aspartate transaminase (AST) levels (p = 0.008). These associations were especially significant in non-obese subjects (n = 191). In a multiple linear regression analysis, age (p = 0.008), insulin sensitivity (p = 0.001), and osteocalcin (p = 0.04) independently contributed to 22% of ALT variance in these latter subjects. In the weight loss study, the increase in circulating osteocalcin concentration (+70.6 ± 29.3 vs. +32 ± 13.5%, p = 0.021) was significantly greater in subjects with the highest decrease in ALT levels, despite similar baseline BMI, insulin resistance and degree of weight loss than remaining subjects. In fact, the change in ALT levels were linearly associated with those of osteocalcin (r = -0.55, p = 0.003). In summary, our findings suggest a bone-liver axis in which osteocalcin might be the active regulator.