BackgroundAngiopoietin-like protein 3 (ANGPTL3) is a major lipoprotein regulator and shows positive correlation with high-density lipoprotein-cholesterol (HDL-c) in population studies and ANGPTL3 mutated subjects. However, no study has looked its correlation with HDL components nor with HDL function in patients with type 2 diabetes mellitus (T2DM).MethodsWe studied 298 non-diabetic subjects and 300 T2DM patients who were randomly recruited in the tertiary referral centre. Plasma levels of ANGPTL3 were quantified by ELISA. Plasma samples were fractionated to obtain HDLs. HDL components including apolipoprotein A-I (apoA-I), triglyceride, serum amyloid A (SAA), phospholipid and Sphingosine-1-phosphate were measured. HDLs were isolated from female controls and T2DM patients by ultracentrifugation to assess cholesterol efflux against HDLs. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, body mass index and lipid lowering drugs were performed in male or female non-diabetic participants or diabetic patients, respectively.ResultsWe demonstrated that plasma level of ANGPTL3 was lower in female T2DM patients than female controls although no difference of ANGPTL3 levels was detected between male controls and T2DM patients. After adjusting for confounding factors, one SD increase of ANGPTL3 (164.6 ng/ml) associated with increase of 2.57 mg/dL cholesterol and 1.14 μg/mL apoA-I but decrease of 47.07 μg/L of SAA in HDL particles of non-diabetic females (p < 0.05 for cholesterol and SAA; p < 0.0001 for apoA-I). By contrast, 1-SD increase of ANGPTL3 (159.9 ng/ml) associated with increase of 1.69 mg/dl cholesterol and 1.25 μg/mL apoA-I but decrease of 11.70 μg/L of SAA in HDL particles of female diabetic patients (p < 0.05 for cholesterol; p < 0.0001 for apoA-I; p = 0.676 for SAA). Moreover, one SD increase of ANGPTL3 associated with increase of 2.11 % cholesterol efflux against HDLs in non-diabetic females (p = 0.071) but decrease of 1.46 % in female T2DM patients (p = 0.13) after adjusting for confounding factors.ConclusionsANGPTL3 is specifically correlated with HDL-c, apoA-I, SAA and HDL function in female non-diabetic participants. The decrease of ANGPTL3 level in female T2DM patients might contribute to its weak association to HDL components and function. ANGPTL3 could be considered as a novel therapeutic target for HDL metabolism for treating diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0450-1) contains supplementary material, which is available to authorized users.

Context The key gut microbial biomarkers for PCOS and how dysbiosis causes insulin resistance and PCOS remain unclear. Objective To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS. Setting and design The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analysed. Phenotype analysis, intestinal flora analysis and global metabolomic profiling of caecal contents were performed on a letrozole (LET)-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing (GTT) was performed on the PCOS mouse model after a 35-day CDCA-treatment. Mice receiving faecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks. Results Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype, insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 (FGF15) levels. PCOS stool-transplanted mice exhibited insulin resistance at ten weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism. Conclusions Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.

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Purpose. Angiopoietin-like proteins (Angptls) play critical roles in biological processes, primarily in lipid metabolism. The functional state of the thyroid has a profound influence on metabolism in the human body. Therefore, the aim of this study was to investigate possible changes in serum Angptl3, 4, and 8 levels in hypothyroid patients. Methods. The study included 29 patients with clinical hypothyroidism, 30 patients with subclinical hypothyroidism, and 29 healthy subjects. Baseline clinical indices, including serum thyroid function tests, were recorded and serum Angptl3, 4, and 8 levels were measured across the three groups. Results. Serum Angptl3 and 8 levels were significantly higher in the hypothyroid groups compared to the control group (p < 0.05). There were no differences in Angptl4 levels among the three groups (p > 0.05). Positive correlations were identified between Angptl3 and high-density lipoprotein cholesterol (r = 0.431, p < 0.001), and there was a negative correlation between Angptl3 and total tri-iodothyronine (TT3) (r = -0.220, p = 0.047) and free tri-iodothyronine (r = - 0.279, p = 0.013) levels. Angptl8 was positively correlated with triglyceride (r = 0.267, p = 0.012) and cholesterol levels (r= 0.235, p = 0.028) but was negatively correlated with tri-iodothyronine (r = -0.24, p = 0.031). Furthermore, we used receiver operating characteristic curve analysis to evaluate the diagnostic performance of Angptl3 and 8 in discriminating thyroid dysfunction. The area under curve for detecting thyroid dysfunction based on Angptl3 and Angptl8 was 0.763. Conclusions. Our data show that serum Angptl3 and 8 levels are increased in clinical and subclinical hypothyroid patients and that Angptl3 and 8 may serve as possible biomarkers of hypothyroid disease.