Serum glypican4 and glycosylphosphatidylinositol-specific phospholipase D levels are associated with adipose tissue insulin resistance in obese subjects with different glucose metabolism status

Objectives: Glypican4 (GPC4) is a novel adipokine associated with obesity and insulin resistance. GPC4 was cleaved by the glycosylphosphatidylinositol-specific phospholipase D (GPLD1) in an anchored site of the glycosylphosphatidylinositol, and then was released into the extracellular environment. Herein, we investigated the changes of serum GPC4 and GPLD1 levels in obese subjects with different glucose metabolism status and their relationship with adipose tissue insulin resistance index (Adipo-IR) in Chinese north populations.

Methods: A total of 221 obese subjects and 37 normal controls (NC) were recruited in this study. Obese subjects were divided into normal insulin (NI) group, hyperinsulinemia (HI) group, impaired glucose tolerance (IGT) group, and type 2 diabetes mellitus (DM) group. Serum GPC4, GPLD1, and adiponectin were determined by commercially available ELISA kits.

Results: Serum GPC4 levels in the HI, IGT, and DM groups were significantly higher than those in the NC and NI groups (2.27 ± 0.58 ng/mL, 2.21 ± 0.60 ng/mL, 2.49 ± 0.67 ng/mL vs. 1.70 ± 0.33 ng/mL, 1.93 ± 0.34 ng/mL, P < 0.05). GPC4 was positively correlated with GPLD1, which was the most important influencing factor of GPC4. Adipo-IR was independently and positively associated with serum GPC4 and GPLD1. For GPC4, after adjustment for confounders, the risk of adipose tissue insulin resistance in subjects with the highest tertile was 2.974-fold that of those with the lowest tertile (OR = 2.974, P = 0.013). For GPLD1, before adjustment for lipids, the increased probability still existed (Model 2, OR = 3.568, P = 0.003).

Conclusion: GPC4 is an adipokine associated with adipose tissue insulin resistance, and its activity may be regulated by GPLD1. GPC4 may be a marker for adipose tissue insulin resistance in Chinese north obese populations.

Keywords: Adiponectin (ADP); Adipose tissue insulin resistance (adipo-IR); Glycosylphosphatidylinositol-specific phospholipase D (GPLD1); Glypican4 (GPC4); Obesity.