ACTA ENDOCRINOLOGICA (BUC)

Background. Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. Method. Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). Results. After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol- 3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3- phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)- like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. Conclusion. Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

Objective. To observe the effect of adiponectin on osteogenesis in type 2 diabetic rats. Methods. The 4th-week-old male SD rats were divided into normal control group (n=18) and diabetic model group (n = 42). Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). The successfully-induced diabetic rats were divided into diabetic group (DM=18) and adiponectin intervention group (APN=18). APN group was injected with APN 10 μg/kg*d. The rats were separately sacrificed at the 4th, 8th and 12th week after the intervention. Bone microstructure and adipose tissue were observed via HE staining. Bone marrow was extracted from one side of the femur, and the supernatant was achieved by centrifugation. After BMD assessed by DXA, the other side of the femur was for further HE staining. Runx-2 expression in the bone marrow cells was detected by RT-PCR. BALP and AOPPs in bone marrow supernatant were assayed by ELISA. AGEs were detected by immunohistochemical staining. Results. With the feeding time over, blood glucose, AOPP, and AGEs were increased, and Runx-2 mRNA, BALP, BMD were decreased in diabetic rat group(P<0.05). Oxidative stress (OS) maker (AOPP) was decreased and osteogenesis makers (Runx2 mRNA, BALP) were increased after intervention with exogenous adiponectin (P<0.05). At the 8th and 12th week, the trabecular bone became thinner and broken, and the fat cell number increased in all 3 groups, especially in the DM group. The adiponectin intervention group showed that the trabecular bone structure was moderately restored. Conclusions. OS is obvious in bone microenvironment in diabetic rats. OS may have an inhibitory effect on regulation of osteogenic differentiation factor Runx2, causing down regulation of osteoblast differentiation and bone formation. Adiponectin may improve OS response and protect the bone structure.

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Background. Blood glucose levels in the human body continuously fluctuate within a certain range. Intermittent hyperglycemia has adverse effects on vascular endothelial\r\ncells and pancreatic beta cells. A few studies have found that blood glucose fluctuation induced apoptosis of both endothelial cells and pancreatic beta cells, possibly due to oxidative stress. This study aimed to determine the\r\neffects of blood glucose fluctuation on hepatocytes in vivo.\r\nMaterials and Methods. To induce intermittent hyperglycemia, rats were intermittently treated with 50% glucose\r\ninjection to fluctuate blood glucose between 5.5 mmol/L and 20.0 mmol/L. The rats with intermittent hyperglycemia were treated with either low dose (0.35 mg/kg?min) or high dose\r\n(0.70 mg/kg?min) N-acetylcysteine (NAC). The rats infused with saline were used as control. Apoptosis was assessed by TUNEL assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver, as well as plasma ALT, AST, TBIL, and IBIL, were examined using colorimetric kits.\r\nResults. Liver function was lower in the rats with intermittent hyperglycemia than in control rats. Hepatocytes exposed to blood glucose fluctuation were more likely\r\nto undergo apoptosis compared to control group (0.07?0.016 vs. 0.015?0.009, P<0.01). The expression of Caspase-3 and\r\ncleaved Caspase-3 was significantly higher in the IHG group than in the SAL group (0.111?0.015 vs. 0.07?0.011; 0.064?0.012 vs. 0.004?0.001, P<0.05).The expression of\r\nBax and the ratio of Bax to Bcl-2 were significantly higher in the IHG group than in the SAL group (0.20?0.05 vs. 0.10?0.02; 0.55?0.20 vs. 0.20?0.05, both P<0.01). When treated with NAC, the liver function of rats with intermittent hyperglycemia improved remarkably, and hepatocyte apoptosis decreased.\r\nConclusion. Blood glucose fluctuation appears to be detrimental to liver function, but this effect can be ameliorated by NAC.

Background. To evaluate iodine status and the prevalence of thyroid disorders in different populations of Zhoushan Island, China.\r\nMethods. A total of 3284 inhabitants of Zhoushan Island were surveyed, including 1389 urban residents, 737 salt workers, 502 peasants, 362 fishermen, and 294 monks from Mount Putuo. All subjects, except for salt workers, consumed iodized salt. A thyroid ultrasound was performed and serum levels of\r\nthyroid hormones and thyroid peroxidase antibody were measured.\r\nResults. The median urinary iodine concentration was significantly higher in subjects who consumed iodized salt than in those who consumed non-iodized salt. No significant differences were noted in the prevalence of thyroid ultrasound abnormalities and functional thyroid disorders between subjects who consumed non-iodized and iodized salt except between salt workers and monks from Mount Putuo. The prevalence of thyroid ultrasound abnormalities differed\r\nsignificantly between males and females and was positively correlated with advanced age (r=0.212, P<0.001).\r\nConclusions. Iodine intake is considered adequate, more than adequate, or excessive amongst the study populations. The\r\nprevalence of both thyroid ultrasound abnormalities and functional thyroid disorders is extremely high in Zhoushan Island. Advanced age and female gender are significant predictors of thyroid ultrasound abnormalities.

Objective. To investigate the correlation between serum levels of 25-hydroxy vitamin D [25(OH)D] and the visceral fat area of patients with type 2 diabetes mellitus (T2DM) in the context of different bone mass. Materials and Methods. A total of 180 patients with T2DM were randomly selected for bone mineral density (BMD) examination. According to the results, they were divided into three groups: T2DM normal bone group (group A); T2DM bone mass reduction group (group B); T2DM osteoporosis group (group C). Result. Serum 25(OH)D levels in NC group, A group, B group and C group decreased in turn, and Visceral fat area (VFA) in group B and group C were significantly higher than those in group A and NC [(29.41±4.87) vs. (22.76±4.23) vs. (17.78±3.61) vs. (9.70±3.01), P<0.05], [(117.76±38.79), (125.08±37.90) vs. (89.79±26.51), (97.53±28.61), P<0.05]. Pearson correlation analysis showed that L1-L4 lumbar vertebrae bone density was positively correlated with 25(OH)D and VFA; left femoral neck bone density was positively correlated with 25(OH)D, and negatively correlated with VFA. Conclusion. Serum 25(OH)D and VFA may be associated with the development of T2DM combined with OP.

We reported that in a 29-year-old male patient with hyperthyroidism, bilateral breast swelling appeared in three days after starting methimazole and gradually aggravated. Several days later, a small amount of transparent liquid could be squeezed out from bilateral mammary glands. Breast ultrasound confirmed gynaecomastia. The level of testosterone, estradiol and luteinizing hormone increased. After the patient continued taking methimazole for a while, gynaecomastia relieved. Testosterone, luteinizing hormone and thyroid functions restored to normal. The possible mechanisms included increased levels of serum total cholesterol and relatively decreased T3 after initiating methimazole.

The role of osteocalcin in atherogenesis is unclear. We investigated the association between osteocalcin and carotid atherosclerosis in Chinese middle-aged and elderly male adults and further determined whether osteocalcin is independently associated with the carotid intima-media thickness (CIMT) in hyperglycemia subgroups. Subjects and methods. A total of 84 male participants (mean age, 59.13 years) were enrolled in groups of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) according to the oral glucose tolerance test. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima–media thicknesses (CIMT) were measured using ultrasonography. The circulating osteocalcin was measured using quantitative enzyme immunoassay. Results. Both IGT and newly diagnosed T2DM groups had significantly lower osteocalcin levels compared with the NGT group (5.01 ± 0.68 μg/L, and 6.173 ± 0.68 ng/mL vs. 11.55 ± 0.57 μg/L, respectively). Multivariate linear stepwise regression analysis demonstrated that waisthip ratio(WHR) (standardized β = -0.408, P = 0.000), 2 hour plasma glucose after glucose load, (PPG) (standardized β = -0.235, P = 0.025), homeostasis model of assessment for insulin resistance index(HOMA-IR) (standardized β = -0.287, P = 0.004), and Glycosylated haemoglobin (HbA1c) (standardized β = -0.250, P = 0.015) were independently and inversely associated with serum osteocalcin in hyperglycemia subgroups; PPG(standardized β = -0.476, P = 0.015), osteocalcin(standardized β = -0.486, P = 0.001) were negatively associated with CIMT, while TG (standardized β = 0.647, P = 0.000) was positively associated with CIMT in T2DM. Conclusion. These results showed that osteocalcin is independently associated with carotid atherosclerosis in men with T2DM. It is tempting to suggest that osteocalcin may be implicated atherosclerosis.