Genetic variants in epoxyeicosatrienoic acid processing and degradation pathways are associated with gestational diabetes mellitus.

AIM: To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women. METHODS: A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses. A genetic risk score (GRS) model based on 12 independent target SNPs associated with GDM was constructed. Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, pre-pregnancy body mass index, history of polycystic ovarian syndrome, history of GDM, and family history of diabetes, with GRS entered both as a continuous variable and categorized groups. The relationship between GRS and quantitative traits was also evaluated. RESULTS: The 12 SNPs in CYP2C8, CYP2C9, CYP2J2, and EPHX2 were significantly associated with GDM after adjusting for covariates (all P < 0.05). The GRS generated from these SNPs significantly correlated with GDM. Furthermore, a significant interaction between CYP2J2 and CYP2C8 in GDM (PInteraction = 0.014, ORInteraction= 0.61, 95%CI 0.41-0.90) was observed. CONCLUSION: We found significant associations between GDM susceptibility and 12 SNPs of the four genes involved in epoxyeicosatrienoic acid processing and degradation pathways in a Chinese population. Subjects with a higher GRS showed higher GDM susceptibility with higher fasting plasma glucose and area under the curve of glucose and poorer ß-cell function.

GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages.

G-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.

Pathology and ultrasound findings in diffuse sclerosing thyroid papillary carcinoma.

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Association between circulating full-length angiopoietin-like protein 8 and non-high-density lipoprotein cholesterol levels in Chinese non-diabetic individuals: a cross-sectional study.

BACKGROUND: Angiopoietin-like protein 8 (ANGPTL8) is a novel hormone involved in the regulation of lipid metabolism and glucose homeostasis. There are inconsistent results regarding the association between ANGPTL8 and lipids in humans. We aimed to investigate the associations between ANGPTL8 and lipids in people without diabetes. METHODS: This was a cross-sectional study of 107 patients with dyslipidemia and 141 patients without. Dyslipidemia diagnosis was based on Chinese guidelines for the prevention and treatment of dyslipidemia in adults. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) were examined. Non-HDL-C was calculated by subtracting HDL-C from TC. Circulating full-length ANGPTL8 concentrations were measured using enzyme-linked immunosorbent assay. Associations between log-transformed circulating full-length ANGPTL8 and serum lipids were examined using multivariate linear regression analysis. RESULTS: Circulating ANGPTL8 concentrations were significantly elevated in patients with dyslipidemia compared with patients without dyslipidemia. Circulating full-length ANGPTL8 concentrations were positively associated with non-HDL-C, TG and TC levels after adjusting for age, gender, body mass index, high-sensitivity C-reactive protein, alanine aminotransferase, and creatinine. CONCLUSION: In people without diabetes, circulating full-length ANGPTL8 concentrations in patients with dyslipidemia were significantly elevated compared with non-dyslipidemia, and ANGPTL8 was positively associated with serum non-HDL-C levels.

[Effect of estrogen on the expression of matrix GLA protein in ovariectomized SD rats].

OBJECTIVE: To investigate the effect of estrogen on expression of matrix GLA protein (MGP) in ovariectomized Sprague-Dawley (SD) rats and the role of estrogen in improving postmenopausal osteoporosis. METHODS: Thirty-six SD female rats were allocated into 3 groups randomly, every 12 rats in ovariectomized group (OVX group), estrogen group (E group) and control group (sham group). Rats in OVX and E group all underwent bilateral ovariectomy, those rats in E group were given by estradiol benzoate intramuscularly after 3 weeks of ovariectomy. Rats in sham group underwent bilateral lipectomy near the ovary. All rats were kept the urine and the serum every three weeks and were sacrificed after 15 weeks. The pathology changes of uterus, lumbar vertebral bones were observed by immunohistochemistry. Bone mineral density (BMD) of lumbar vertebra of rats was determined by dual energy X ray absorptiometry (DEXA). The content of MGP in serum and urine was determined by ELISA. Expression of undercarboxylated matrix GLA Protein (MGP) was detected by immunohistochemistry. Relative quantification of MGP mRNA expression in lumbar vertebra bone was detected by Fluorescent real-time quantitative polymerase chain reaction. RESULTS: (1) After 15 weeks of ovariectomized, the endometrium of uterus and lumbar vertebra exhibit remarkable pathologic changes in OVX group. The serum estrogen of (454 ± 66) pmol/L in OVX group were lower than in (527 ± 77) pmol/L in sham group and (556 ± 80) pmol/L in E group significantly (P < 0.05). The BMD of lumbar vertebra of (0.263 ± 0.030) g/cm(2) in OVX group were lower than (0.295 ± 0.024) g/cm(2) in sham group and (0.279 ± 0.024) g/cm(2) in E group significantly (P < 0.01). (2) The serum MPG protein in OVX group and E group showed decreased trends after ovariectomized, which were (104 ± 64) ng/L in OVX group and (134 ± 6) ng/L in E group at 9 weeks, which reached statistical difference (P < 0.05). However, MGP in urine in sham group did not exhibit significant difference after 15 weeks of surgery (P > 0.05). The MGP in urine of E group showed increased trends after 12 weeks of surgery, which reached (110.0 ± 3.4) ng/L at 15 weeks, in the mean time, it was found that (86.5 ± 2.5) ng/L of MGP in urine in OVX group, which showed significant difference (P < 0.05). (3) MGP could be observed in lumbar vertebra in OVX group by immunochemistry staining. In the other two groups, the expression of MGP was not dominant. (4) Relative quantification of MGP mRNA expression in lumbar vertebra was defined as 1 in OVX group, when compared with 0.289 ± 0.260 in E group and 0.103 ± 0.098 in sham group, the difference showed statistically significant (P < 0.01). CONCLUSION: Estrogen could increase the expression of MGP mRNA and protein in ovariectomized rats and might play an important role in improving postmenopausal osteoporosis.