Circulating ANGPTL8/Betatrophin Is Increased in Obesity and Reduced after Exercise Training

Abstract

ObjectiveANGPTL8 is a liver and adipose tissue produced protein that regulates the level of triglyceride in plasma as well as glucose homeostasis. This study was designed to evaluate the level of ANGPTL8 in obese and non-obese subjects before and after exercise training.MethodsA total of 82 non-obese and 62 adult obese were enrolled in this study. Subjects underwent a three months of exercise training. Both full length and C-terminal 139–198 form of ANGPTL8 were measured by ELISA.ResultsOur data show that the full length ANGPTL8 level was increased in obese subjects (1150.04 ± 108.10 pg/mL) compared to non-obese (775.54 ± 46.12) pg/mL (p-Value = 0.002). C-terminal 139–198 form of ANGPTL8 was also increased in obese subjects 0.28 ± 0.04 ng/mL vs 0.20 ± 0.02 ng/mL in non-obese (p-value = 0.058). In obese subjects, the levels of both forms were reduced after three months of exercise training; full length was reduced from 1150.04 ± 108.10 pg/mL to 852.04 ± 51.95 pg/mL (p-Values 0.015) and c-terminal form was reduced from 0.28 ± 0.04 ng/mL to 0.19 ± 0.03 ng/mL (p-Value = 0.058). Interestingly, full length ANGPTL8 was positively associated with fasting blood glucose (FBG) in non-obese (r = 0.317, p-Value = 0.006) and obese subjects (r = 0.346, p-Value = 0.006) C-terminal 139–198 form of ANGPTL8 on the other hand, did not show any correlation in both groups.ConclusionIn conclusion, our data demonstrate that ANGPTL8 was increased in obesity and reduced after exercise training supporting the potential therapeutic benefit of reducing ANGPTL8. The various forms of ANGPTL8 associated differently with FBG suggesting that they have different roles in glucose homeostasis.

Hepatocellular Carcinoma‐Associated Protein TD26 Interacts and Enhances Sterol Regulatory Element‐Binding Protein 1 Activity to Promote Tumor Cell Proliferation and Growth

“…It has been reported that TD26 may also be subjected to a partial degradation to generate a short fragment carrying aa from C‐terminal 139 to 198 . A previous study has demonstrated that this C‐terminal short form and full‐length of TD26 are both increased in obese people and only the full‐length TD26, but not the C‐terminal short form, is positively associated with elevated fasting blood glucose . Interestingly, in the present study, we show that the C‐terminus of TD26 (from aa 121‐198) is essential for TD26 interacting with SREBP1.…”

“…Although TD26 has been initially detected to be highly expressed in HCC tissues since 2004, the functional studies on TD26 are mainly focused on diabetes and obesity because of its physiological role in glucose homeostasis and lipid metabolism . Several studies have reported increased TD26 levels in obesity and/or diabetes patients . In addition, a recent study indicates increased TD26 levels in patients with cirrhosis .…”

Dynamic Changes of Betatrophin and Its Potential Effect on β-cells in Spontaneously Developed or Streptozocin-induced Diabetes Monkeys

“…Betatrophin levels were also affected by other parameters, such as triglycerides [38,43]. In this study, TG and TC were also significantly higher in naturally developed diabetes NHPs, which might also be the factors affecting betatrophin levels (Figures 1 and 3) [44].…”

ANGPTL8 (betatrophin) role in diabetes and metabolic diseases

“…We have recently published a large human cohort study that showed a positive association between ANGPTL8 and BMI, and also with waist/hip ratio in non‐diabetic people . In another study, we also showed that ANGPTL8 was increased in obese people, but its level was reduced after exercise . In this study, we looked at both forms of ANGPTL8 which has been called the C‐terminal 139‐198 and the full length form of ANGPTL8 due to the different ELISA antibodies used to measure its plasma level.…”