Huijuan Zhu

Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice

OBJECTIVE To explore the effects of zinc-alpha2-glycoprotein (ZAG) on body weight and body fat in high-fat-diet (HFD)-induced obesity in mice and the possible mechanism. METHODS Thirty-six male mice were fed with standard food (SF) (n = 9) and HFD (n = 27), respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) in liver tissue were determined by reverse transcription-polymerase chain reaction. RESULTS Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice (0.51 +/- 0.10 AU vs. 0.75 +/- 0.07 AU, P < 0.01). Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r = -0.56, P < 0.001), epididymal fat mass (r = -0.67, P < 0.001), percentage of epididymal fat (r = -0.65, P < 0.001), and increased weight (r = -0.57, P < 0.001) in simple SF- and HFD-fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididymal fat. Furthermore, FAS mRNA expression decreased (P < 0.01) and HSL mRNA expression increased (P < 0.001) in the liver in ZAG over-expressing mice. CONCLUSIONS ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.

Transsphenoidal surgery in a patient with acromegaly and McCune–Albright syndrome: application of neuronavigation

The McCune-Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.

Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice.

Purpose This study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models. Methods Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment. The BAT function was correlated with the body weight and blood glucose levels. Results Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = −0.71, P = 0.003) and DM mice (r = −0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45). Conclusion The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.

Association of myostatin gene polymorphisms with obesity in Chinese north Han human subjects

CONTEXT Myostatin (MSTN) is a member of the TGF-β superfamily of signal transduction proteins, which plays an important role in muscular growth and lipid metabolism. OBJECTIVE To study the association of myostatin gene polymorphisms with obesity in Chinese north Han human subjects. DESIGN 297 healthy and 606 over-weight/obesity Chinese north Han subjects were selected as healthy control group and overweight/obesity group, respectively. The methods of DNA Sequencing, Restriction Fragment Length Polymorphism (RFLP) and TaqMan® probe were used to screen myostatin gene SNPs and clarify genotype in every individual. RESULTS Total 11 SNPs in MSTN gene were identified by DNA sequencing and three SNPs including rs35781413 (G/A), rs3791783 (A/G) and rs3791782 (A/G) were selected for further study in total 903 samples. The results showed that the frequency of AA genotype of rs3791783 A/G SNP was significantly higher (56.4% vs. 50.8%) and the frequency GG genotype was significantly lower (3.2% vs. 6.7%) in overweight/obese patients than in normal weight subjects. A logistic regression analysis under a recessive inheritance model (AA+AG vs.GG) demonstrated that the Odd ratio for AA+AG vs.GG were 1.985 (95% CI 1.078-3.643; P=0.029). Among three genotypes of rs3791783, the subjects with AA genotype have much more higher body weight, BMI, waist circumference, TC, TG and LDL-C than those with GG genotype. CONCLUSIONS Our data firstly suggest that genetic variant rs3791783 A/G in myostatin gene are associated with obesity. The A allele carriers in rs3791783 SNP have an increased susceptibility to obesity compared with the G allele carriers. Participants with AA genotype in rs3791783 SNP site will have higher risk suffered from overweight or obesity than those with GG genotype.

The role of three-dimensional printed models of skull in anatomy education: a randomized controlled trail

Three-dimensional (3D) printed models represent educational tools of high quality compared with traditional teaching aids. Colored skull models were produced by 3D printing technology. A randomized controlled trial (RCT) was conducted to compare the learning efficiency of 3D printed skulls with that of cadaveric skulls and atlas. Seventy-nine medical students, who never studied anatomy, were randomized into three groups by drawing lots, using 3D printed skulls, cadaveric skulls, and atlas, respectively, to study the anatomical structures in skull through an introductory lecture and small group discussions. All students completed identical tests, which composed of a theory test and a lab test, before and after a lecture. Pre-test scores showed no differences between the three groups. In post-test, the 3D group was better than the other two groups in total score (cadaver: 29.5 [IQR: 25–33], 3D: 31.5 [IQR: 29–36], atlas: 27.75 [IQR: 24.125–32]; p = 0.044) and scores of lab test (cadaver: 14 [IQR: 10.5–18], 3D: 16.5 [IQR: 14.375–21.625], atlas: 14.5 [IQR: 10–18.125]; p = 0.049). Scores involving theory test, however, showed no difference between the three groups. In this RCT, an inexpensive, precise and rapidly-produced skull model had advantages in assisting anatomy study, especially in structure recognition, compared with traditional education materials.

Efficacy and Safety of Bromocriptine-QR in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Bromocriptine-QR (quick release) is a novel treatment for type 2 diabetes. The objective of this study is to assess the efficacy and safety of bromocriptine-QR in adults with type 2 diabetes mellitus based on randomized controlled trials published in peer-reviewed journals or as abstracts. We performed a comprehensive literature search of MEDLINE, Pubmed, Web of Science, EMBASE, and the Cochrane Library up to May 2015. Randomized controlled trials of bromocriptine-QR therapy in type 2 diabetes mellitus were eligible. Two reviewers independently assessed the eligibility of trials based on predefined inclusion criteria. Information was collected concerning basic study data, patient characteristics, efficacy and safety outcomes, and methodological quality. Bromocriptine-QR add-on therapy lowered hemoglobin A1c compared with placebo (weighted mean difference, - 6.52 mmol/mol; 95% CI, - 8.07 to - 4.97 mmol/mol). Bromocriptine-QR exhibited an increase in achieving an HbA1c level ≤ 53 mmol/mol (≤ 7.0%) (32.0 vs. 9.5%; odds ratio, 4.57; 95% CI, 2.42-8.62). Fasting plasma glucose was reduced with bromocriptine-QR compared with placebo (weighted mean difference,-1.04 mmol/l; 95% CI,-1.49 to-0.59 mmol/l). Moreover, bromocriptine-QR had neutral effects on postprandial glycemia, Body Mass Index (BMI), and lipid profile. Bromocriptine-QR had more gastrointestinal side effects of nausea and vomiting. Bromocriptine-QR had no increased risk of hypoglycemia, hypotension, or cardiovascular effects. Bromocriptine-QR therapy offers an alternative option to currently available antidiabetic agents for type 2 diabetes mellitus adults. Neither hypoglycemia nor other metabolic changes occur with this drug. More data for long-term efficacy and safety are needed for further observation.

rs4215 SNP in zinc-α2-glycoprotein gene is associated with obesity in Chinese north Han population ☆

OBJECTIVE Zinc-α2-glycoprotein (ZAG) has been identified recently as a novel adipokine due to its close link with lipid and glucose metabolism, as well as regulation of body weight. The aim of our present study is to investigate the ZAG genetic polymorphism association with obesity in Chinese north Han population. DESIGN AND METHODS Five SNPs of ZAG gene including rs2247607 (A>T), rs4727442 (G>T), rs4215 (A>G), rs2527923 (C>T) and rs2527882 (C>T) were genotyped in 648 overweight/obese patients and 313 healthy controls by TaqMan-PCR methods. Crosstabs statistical analysis method with subjects stratifying by age (≦ 30 y, 31-45 y, ≧ 46 y) and gender was used. RESULTS The results showed the constitution of three genotype frequencies in rs4215 (A>G) site significantly differs in male subgroup (aged 31-45 y) between overweight/obese and healthy control group (χ(2)=6.401, P=0.041). GG genotype frequency in overweight/obese group is 19.3% which is much higher than 6.1% in healthy control group. Further statistical analysis under a recessive inheritance model demonstrated odd ratio (OR) for GG vs. AA+AG in overweight/obese group was 3.674 (95% CI 1.049-12.866; P=0.035). Among three genotypes of rs4215, the subjects with GG genotype have much more higher body weight, BMI, waist circumference and SBP. CONCLUSION Our data, for the first time, suggest the genotypes of rs4215 in ZAG gene are significantly associated with obesity in Chinese north Han population. GG genotype subjects in rs4215 site have an increased susceptibility to obesity when compared with the AA+AG genotype subjects.

The impact of maternal hypothyroidism during pregnancy on neonatal outcomes: a systematic review and meta-analysis.

Abstract The effects of maternal hypothyroidism on neonatal outcomes were not definitely confirmed. We conduct a systematic review of the literatures on the impact of maternal hypothyroidism on neonatal outcomes. We searched Pubmed, Embase and the Cochrane Controlled Trials Register databases complemented by manual searches in article references without language restrictions published from 1946 to April 2015. Nine trials are included. For preterm birth in pregnancies of hypothyroidism women, there is an increased tendency (RR 1.18; 95% CI 0.99 to 1.40; p = 0.06). The same result is seen relating to the low birth weight (RR 1.31; 95% CI 1.00 to 1.72; p = 0.05). Regarding small for gestational age there is no significant increase. Children who were born from mothers with hypothyroidism during pregnancy have increased birth weight (MD 32.35, 95% CI 7.46 to 57.24; p = 0.01). The impact of maternal hypothyroidism shows a trend of reduced risk of large for gestational age (RR 1.17; 95% CI 0.99 to 1.38; p = 0.06). Our review suggests that mothers with hypothyroidism during pregnancy are more likely to give birth to children with higher birth weight or LGA, and L-T4 supplementation should be recommended. The risk of preterm birth and low birth weight also tends to be higher in children with hypothyroidism mothers.

Safety and efficiency of SGLT2 inhibitor combining with insulin in subjects with diabetes: Systematic review and meta-analysis of randomized controlled trials

Background: We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM). Methods: We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently. The risk of bias was assessed by Cochrance System Evaluate Method and Q test was used to evaluate the heterogeneity between studies. We used random effect model to analyze the results by Revman 5.3. This meta-analysis has been registered at online public registry PROSPERO (registration number is: CRD42017054718). Results: Nine trials including 3069 patients were analyzed. Compared with control group, SGLT2 inhibitor produced absolute reduction in glycosylated hemoglobin A1c (HbA1c) (MD −1.35%, 95% confidence interval [CI] [−2.36 to −0.34], P = .009), fasting plasma glucose (FPG) (MD −1.01 mmol/L, 95%CI [−1.98 to 0.04], P = .04), insulin dosage (MD −4.85 U/24 hours, 95%CI [−7.42 to −2.29], P = .002), and body weight (MD −2.30 kg, 95%CI [−3.09 to −1.50], P < .00001). But the risk of hypoglycemia (OR 1.18, 95%CI [0.86, 1.61], P = . 30) and urinary tract infection (UTI) (OR 1.34, 95%CI [0.79, 2.27], P = .28) were proved as no difference and genital tract infection (GTI) with SGLT2 inhibitors was higher than control group (OR 2.96, 95%CI [1.05, 8.37], P = .04), in which cases were mild and responded to the therapy. According to the subgroup analysis, SGLT2 inhibitors had a similar effect in effective factors of both T1DM and T2DM, but the risk of GTI mainly increased in T2DM versus T1DM (T1DM OR 0.27 [0.01, 7.19], P = .43 vs T2DM OR 4.28 [2.00, 9.16], P = .0002). Conclusion: SGLT2 inhibitors have improved the HbA1c, FPG, and body weight when combined with insulin and decreased the dose of insulin without increasing the risk of hypoglycemia. However, SGLT2 inhibitor was proved to be related to the events of GTI, despite SGLT2 inhibitors appeared to be well tolerated. We suggest that more monitoring should be done to prevent the events of GTI, and more randomized controlled trials should be planned next step.

Preconception TSH and pregnancy outcomes: a population‐based cohort study in 184 611 women

Whether subclinical hypothyroidism adversely impacts pregnancy outcomes is inconclusive, and limited data are available on the optimal TSH range in women planning pregnancy.