Identification of circulating apolipoprotein M as a new determinant of insulin sensitivity and relationship with adiponectin

Abstract

Background: Most adipokines are up-regulated with obesity and promote metabolic dysfunction, while few, like adiponectin, are down-regulated during adipose tissue expansion and probably protect against obesity-related disorders. High adiponectin is linked to low inflammation and insulin sensitivity. Similarly, apolipoprotein M (apoM) was recently identified as an adipokine for which the expression in adipose tissue is positively associated with metabolic health. Our aim was to compare circulating levels of apoM to those of adiponectin in overweight and obese individuals with respect to metabolic parameters and insulin sensitivity. Methods: Adiponectin and apoM and were measured in a cross-sectional study including 169 overweight men and in a surgery-induced weight loss program including 13 obese patients of both sexes who underwent sleeve gastrectomy. Correlations between the homeostasis model assessment of insulin resistance (HOMA-IR) index, bioclinical parameters, adiponectin and apoM levels, and lifestyle habits were assessed using Spearman correlation coefficients. Multiple regression analyses of HOMA-IR were performed. Results: In overweight men, plasma adiponectin and apoM were lower in participants with diabetes. The apoM level did not correlate with that of adiponectin and was higher in individuals with dyslipidemia. Similar to adiponectin, apoM was negatively associated with HOMA-IR (r = -0.29), hs-CRP (r = -0.28) and HDL markers (HDL-C, r = 0.32; apoA-I, r = 0.32). Unlike adiponectin, apoM did not correlate with triglyceride levels but was positively associated with LDL markers (LDL-C, r = 0.27; apoB100, r = 0.20) and negatively with fat mass (r = -0.26) and age (r = -0.25). In multiple regression models, apoM was the only negative determinant of HOMA-IR, while adiponectin did not contribute to HOMA-IR variability. Accordingly, while sleeve gastrectomy improved insulin sensitivity, change in HOMA-IR at one year of follow-up was strongly negatively associated with change in the level of circulating apoM (r = -0.71) but not with change in the adiponectin level. Conclusions: Both circulating apoM and adiponectin are negatively correlated with bioclinical variables associated with obesity, inflammation, and insulin resistance. Unexpectedly, apoM, but not adiponectin, was a negative determinant of HOMA-IR. We identified for the first time circulating apoM as a novel biomarker of insulin sensitivity.