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

Abstract

BackgroundHypertriglyceridemia 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.MethodsA 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.ResultsIn 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).ConclusionIn 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.

Plasma ANGPTL‐4 is Associated with Obesity and Glucose Tolerance: Cross‐Sectional and Longitudinal Findings

“…Our data show that the increase in ANGPTL‐4 levels in obesity is higher in those individuals with ATG, and that there is a positive correlation between ANGPTL‐4 and HOMA‐IR and HbA1C. Similarly, two recent articles showed that plasma levels of ANGPTL‐4 are increased in T2D subjects with respect to nondiabetic individuals . In concordance with these findings in humans, ANGPTL‐4 transgenic mice showed a worsening of glucose metabolism when fed a high‐fat diet .…”

“…Similarly, two recent articles showed that plasma levels of ANGPTL-4 are increased in T2D subjects with respect to nondiabetic individuals. [22,32] In concordance with these findings in humans, ANGPTL-4 transgenic mice showed a worsening of glucose metabolism when fed a high-fat diet. [3] Altogether, it seems that elevated levels of ANGPTL-4 are related to a poor glucose tolerance.…”

“…[20] Surprisingly, despite its role in energy homeostasis and its nutritional-dependent regulation, [2,4,11] the role of ANGPTL-4 in human obesity and T2D has barely been studied. The few studies assessing the relationship between ANGPTL-4 levels with obesity-associated parameters in humans have generally shown a positive correlation between ANGPTL-4 and BMI, [7,21,22] and only one group found an inverse correlation with obesity. [23] In addition, polymorphisms in the ANGPTL-4 gene were associated with higher percentage of body fat, [24] supporting the role of ANGPTL-4 in human obesity.…”

Fenofibrate Exerts Protective Effects in Diabetic Retinopathy via Inhibition of the ANGPTL3 Pathway

“…13 Our current findings showed that ANGPTL3 expression was upregulated under high glucose stimulation in HRMECs and in the retinas of diabetic rats. To investigate the relationship between ANGPTL3 and diabetic retinopathy, we measured the protein and RNA expression levels of genes involved in inflammation and apoptosis in both HRMECs and rat retinas before and after ANGPTL3 siRNA intervention under high glucose conditions.…”

Angiopoietin-like 8 (Angptl8) controls adipocyte lipolysis and phospholipid composition

“…Most of the recent studies suggest that plasma ANGPTL8 levels are elevated in type 2 diabetes (T2D), insulin resistance or obesity (Abu-Farha et al, 2016;Chen et al, 2015;Fu et al, 2014). However, ANGPTL8 was found to be the the most strongly insulin-induced individual gene in human WAT in vivo (Nidhina Haridas et al, 2015;Soronen et al, 2012), suggesting that, apart from its function in the circulation, it may also execute an unknown intracellular function in adipocytes.…”