Hepatokine leukocyte cell-derived chemotaxin 2 as a biomarker of insulin resistance, liver enzymes, and metabolic dysfunction-associated steatotic liver disease in the general population

Aims/introduction: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-associated hepatokine that causes skeletal muscle insulin resistance. Since LECT2 is up-regulated by the inactivation of the energy sensor AMPK in the liver, we hypothesized that LECT2 has potential as a biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we investigated whether circulating LECT2 levels are associated with insulin sensitivity, liver enzymes, and MASLD.

Materials and methods: This cross-sectional study included 138 Japanese individuals. Plasma LECT2 levels were measured using fasting blood samples. B-mode ultrasonography was used to assess hepatic steatosis.

Results: The mean age and body mass index (BMI) of participants were 63.5 ± 10.2 years and 23.0 ± 3.1 kg/m², respectively. Higher LECT2 levels positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) values and negatively correlated with the quantitative insulin sensitivity check index (QUICKI) among all participants (HOMA-IR; non-standardized β (B) = 6.38, P < 0.01: QUICKI; B = -161, P < 0.01). These correlations were stronger in the low BMI group (HOMA-IR; B = 13.85, P < 0.01: QUICKI; B = -180, P < 0.01). LECT2 levels also positively correlated with gamma-glutamyl transferase levels (B = 0.01, P = 0.01) and alanine aminotransferase levels (B = 0.33, P = 0.02). Higher LECT2 levels correlated with the prevalence of MASLD (odds ratio = 1.14, P = 0.02).

Conclusions: The present results suggest the potential of plasma LECT2 levels as a biomarker for insulin resistance in individuals who are not overweight and the prevalence of MASLD in the general population.