Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D

Hypertriglyceridemia is associated with increased risk for cardiovascular diseases and type 2 diabetes (T2D). Angiopoietin like proteins particularly 3, 4 and recently 8 are well established regulators of plasma triglyceride level through regulating the activity of lipoprotein lipase. Plasma level and association between ANGPTL3, 4 and 8 is not well established in human subjects. This study was designed to establish the level of these proteins in plasma and adipose tissues and investigate the association between ANGPTL8 with ANGPTL3 and 4 in T2D and non-diabetics subjects.

A total of 235 subjects were enrolled in this study, 144 non-diabetics and 91 T2D. ANGPTL 3, 4 and 8 levels were measured in plasma by ELISA and using real time RT-PCR in adipose tissues.

In this study, we showed that ANGPTL3, 4 and 8 were higher in T2D subjects. Dividing the non-diabetic subjects according to their BMI showed higher level of ANGPTL3, 4 and 8 in obese subjects compared to non-obese subjects. No significant difference was observed between the T2D subjects. ANGPTL8 was showed positive correlation with ANGPTL3 in the non-diabetic subjects in the non-obese (r = 0.2437, p-Value = 0.0543) and obese subjects (r = 0.418, p-Value = 0.0125). No association was observed in the T2D subjects. On the other hand, ANGPTL4 was positively associated with the obese subjects in both the non-diabetics (r = 0.3322, p-Value = 0.0316) and the obese T2D subjects (r = 0.3161, p-Value = 0.0211).

In conclusion, our data shows that ANGPTL3, 4 and 8 are increased in obesity and T2D. ANGPTL8 associates with ANGPTL3 in the non-diabetic subjects while it associated more with ANGPTL4 in the obese and T2D subjects. Taken together, this data highlight the role of these proteins in metabolic diseases and how they interact with each other's under different physiological and pathophysiological conditions.