Higher Levels of ANGPTL5 in the Circulation of Subjects With Obesity and Type 2 Diabetes Are Associated With Insulin Resistance

Abstract

Objective: The family of angiopoietin-like proteins (ANGPTLs) is composed of eight ANGPTLs members that are involved in regulating various metabolic processes and have been implicated in type 2 diabetes (T2D) and obesity. ANGPTL5 is an understudied member of this family that has been suggested to regulate triglyceride metabolism with a potential role in obesity. This study was designed to investigate the expression levels of ANGPTL5 protein in the circulation of subjects with obesity and T2D. Methods: A total of 204 subjects were enrolled in this cross-sectional study, of which 95 had diagnosed T2D and 109 did not (non-T2D). Within the non-T2D group, 39 subjects were obese (BMI ≥ 30 Kg/m 2 ) and 70 were not (BMI < 30 Kg/m 2 ). Among subjects with T2D, 61 were obese and 34 were non-obese. Circulating ANGPTL5 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: In this study, we showed that ANGPTL5 levels were higher in the plasma of subjects with T2D [mean ± standard error of the mean (SEM): 5.78 ± 2.70 ng/mL] compared with individuals without T2D (mean ± SEM: 4.42 ± 2.22 ng/mL; P < 0.001). Obese and non-T2D subjects had significantly higher levels of ANGPTL5 (mean ± SEM: 5.115 ± 0.366 ng/mL) compared with non-obese, non-T2D subjects (mean ± SEM: 4.02 ± 0.271 ng/mL; P = 0.003). Similarly, among subjects with diagnosed T2D, those who were obese had higher ANGPTL5 plasma levels than non-obese subjects, although this difference did not reach statistical significance ( P = 0.088). Correlation analyses revealed that ANGPTL5 levels positively associated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), triglycerides (TGL), and insulin resistance as measured by HOMA-IR. Conclusion: our data shows for the first time that circulating ANGPTL5 levels were higher in obese individuals and those with T2D. Further analysis will be required to better understand the interaction between ANGPTL5 and other metabolic related biomarkers to shed more light on its role in diabetes and obesity.

Correlation of circulating ANGPTL5 levels with obesity, high sensitivity C-reactive protein and oxidized low-density lipoprotein in adolescents

“…Elevated levels of ANGPTL proteins have been linked to obesity, diabetes and metabolic syndrome 11,13,16,17,19 . We recently demonstrated an increase in circulating plasma ANGPTL5 levels in obese vs non-obese adults as well as in adults with and without diabetes 23 . In the current study, we investigated the role of ANGPTL5, a less studied member of the ANGPTL protein family, in childhood obesity and its association with the metabolic markers HsCRP and Ox-LDL.…”

Elevated Plasma Angiopoietinlike Protein 5 (ANGPTL5) Is More Positively Associated with Glucose Metabolism Disorders in Patients with Metabolic Syndrome

“…In 2019, Alghanim et al found that the plasma ANGPTL5 concentration of obese patients was higher than that of nonobese patients; compared with nonobese patients with type 2 diabetes, the plasma ANGPTL5 concentration was significantly higher in obese patients with type 2 diabetes, which was closely related to insulin resistance [ 19 ]. In 2020, it was further found that ANGPTL5 levels were elevated in obese adolescents, and associated with cardiovascular disease risk factors including hs-CRP and oxidized LDL [ 21 ].…”

“…Recently, Alghanim et al found that compared with nonobese type 2 diabetes patients, the plasma ANGPTL5 concentration was increased in obese patients with type 2 diabetes. It was also positively correlated with fasting plasma glucose (FPG), TG, and homeostatic model assessment of insulin resistance (HOMA-IR) [ 19 ]. These suggest that ANGPTL5 may be related to glucose and lipid metabolism, obesity, and diabetes, and is expected to become one of the important biomarkers for the above diseases.…”

Emerging roles of angiopoietin‐like proteins in inflammation: Mechanisms and potential as pharmacological targets

“…ANGPTL5 has been suggested to be associated with inflammation based on the elevated level of circulating ANGPTL5 found in obese individuals and patients with T2DM (Alghanim et al, 2019). Moreover, elevation of circulating ANGPTL5 is correlated with higher hs-CRP, a marker of low-grade chronic inflammation (Alghanim et al, 2019). Further investigation is needed to elucidate whether and how ANGPTL5 is involved in inflammation.…”