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. 2016 Feb 5:15:25.
doi: 10.1186/s12933-016-0346-0.

Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome

Mohamed Abu-Farha  1 , Jehad Abubaker  2 , Irina Al-Khairi  3 , Preethi Cherian  4 , Fiona Noronha  5 , Sina Kavalakatt  6 , Abdelkrim Khadir  7 , Kazem Behbehani  8 , Monira Alarouj  9 , Abdullah Bennakhi  10 , Naser Elkum  11
Affiliations

Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome

Mohamed Abu-Farha et al. Cardiovasc Diabetol. .

Abstract

Background: ANGPTL8 also called betatrophin is a regulator of lipid metabolism through its interaction with ANGPTL3. It has also been suggested to play a role in insulin resistance and beta-cell proliferation. Based on its function, we hypothesized that ANGPTL8 will play a role in Metabolic Syndrome (MetS). To test this hypothesis we designed this study to measure ANGPTL8 level in subjects with MetS as well as its association with high sensitivity C-reactive protein (HsCRP) level in humans.

Methods: ANGPTL8 level was measured using ELISA in subjects with MetS as well as their controls, a total of 1735 subjects were enrolled. HsCRP was also measured and its association with ANGPTL8 was examined.

Results: ANGPTL8 level was higher in subjects with MetS 1140.6 (171.9-11736.1) pg/mL compared to 710.5 (59.5-11597.2) pg/mL in the controls. Higher levels of ANGPTL8 were also observed with the sequential increase in the number of MetS components (p value = <0.0001). ANGPTL8 showed strong positive correlation with HsCRP (r = 0.15, p value = <0.0001). Stratifying the population into tertiles according to the level of HsCRP showed increased ANGPTL8 level at higher tertiles of HsCRP in the overall population (p value = <0.0001).A similar trend was also observed in MetS and non-MetS subjects as well as in non-obese and obese subjects. Finally, multiple logistic regression models adjusted for age, gender, ethnicity and HsCRP level showed that subjects in the highest tertiles of ANGPTL8 had higher odds of having MetS (odd ratio [OR] = 2.3, 95 % confidence interval [CI] = (1.6-3.1), p value <0.0001.

Conclusion: In this study we showed that ANGPTL8 is increased in subjects with MetS and it was significantly associated with HsCRP levels in different subgroups highlighting its potential role in metabolic and inflammatory pathways.

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Figures

Fig. 1
Fig. 1
Circulating level of ANGPTL8 in subjects MetS. a Least square means of plasma level of ANGPTL8 in MetS vs non-MetS subjects. b Least square means of plasma level of ANGPTL8 according to the number of MetS components
Fig. 2
Fig. 2
Association between ANGPTL8 and HsCRP according to MetS. a least square means of circulating level of ANGPTL8 according to HsCRP tertiles in all the subjects. b ANGPTL8 level in non-MetS subjects according to HsCRP tertiles. c ANGPTL8 level in MetS subjects according to HsCRP tertiles. Tertile values of HsCRP are expressed as T1 (<1.39 μg/mL), T2 (1.39–4.07 μg/mL), and T3 (>4.07 μg/mL)
Fig. 3
Fig. 3
Association between ANGPTL8 and HsCRP according to obesity. a least square means of circulating level of ANGPTL8 according to HsCRP tertiles in non-obese subjects. b ANGPTL8 level in obese subjects according to HsCRP tertiles. Tertile values of HsCRP are expressed as T1 (<1.39 μg/mL), T2 (1.39–4.07 μg/mL), and T3 (>4.07 μg/mL). BMI between 18.5–29.9 was considered non-obese while BMI equal to or higher than 30, was considered obese
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