Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity

Abstract

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25–74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Serum ANGPTL8 and ANGPTL3 as Predictors of Triglyceride Elevation in Adult Women

“…The data so far are controversial; some but not all reports demonstrated higher levels of ANGPTL8 in obese patients than in non-obese. In the previous study from our group, we noticed significantly higher levels of ANGPTL8 in apparently healthy women with obesity whereas ANGPTL3 levels were comparable [21].…”

“…This analysis was adjusted for several variables but not age and gender [20]. In our previous study we observed a significant positive correlation between ANGPTL3 and CRP and BMI in males whereas in females no relationship between these variables was found [21]. Certainly, the mechanisms linking ANGPTL3 and low-grade inflammation remain unclear and require further studies; however, we suggest that gender-dependent differences may contribute.…”

“…However, we included only apparently healthy non-diabetic women and both subgroups had very similar glycemic status, CRP and HDL-C levels. We had no access to anthropometric measures and did not assess thyroid function but, referring to the recent data from our group, we may assume that most of the subjects were euthyroid [21]. The frequency of obesity was slightly higher in the postmenopausal than in premenopausal group (19% and 13%, respectively), but their BMI was comparable.…”

Energy Homeostasis Gene Nucleotide Variants and Survival of Hemodialysis Patients—A Genetic Cohort Study

“…To date, there have been no studies on the putative associations between DOCK6 and diabetes or CKD. However, multiple studies have revealed that the levels of ANGPTL8 are higher in patients with diabetic nephropathy and obesity as well as positively correlated with atherogenic markers and carotid intima-media thickness [55][56][57][58]. Another study by Zou et al revealed that older subjects with higher circulating ANGPTL8 levels were at an increased risk of kidney function decline, which might suggest a role of ANGPTL8 in the pathogenesis of CKD [59].…”

Novel Pharmaceutical and Nutraceutical-Based Approaches for Cardiovascular Diseases Prevention Targeting Atherogenic Small Dense LDL

“…Recent studies in apparently healthy subjects [61] and patients with diabetes [62] have reported a positive association between increased plasma ANGPTL3 and sdLDL particles. These findings suggest possible beneficial effects of ANGPTL3 inhibition on sdLDL, which should be verified in the future.…”