Hualing Zhai

Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)).

Recent studies have suggested an association between vitamin D and non-alcoholic fatty liver disease (NAFLD); however, some results are subject to debate. This study was carried out to evaluate the correlation between NAFLD and vitamin D in men and women in East China. The data were obtained from a cross-sectional study that focused on the health and metabolic status of adults in sixteen areas of East China. According to ultrasonic assessments, the patients were divided into normal and NAFLD groups. Demographic characteristics and biochemical measurements were obtained. Binary logistic regression analysis was used to explore the association. In total, 5066 subjects were enrolled, and 2193 (43·3 %) were diagnosed with NAFLD; 84·56 % of the subjects showed vitamin D deficiency. Subjects with high vitamin D levels had a lower prevalence of NAFLD, particularly male subjects. Within the highest quartile of vitamin D levels, the prevalence of NAFLD was 40·8 %, whereas the lowest quartile of vitamin D levels showed a prevalence of 62·2 %, which was unchanged in women across the vitamin D levels. Binary logistic analysis showed that decreased vitamin D levels were associated with an increased risk of NAFLD (OR 1·54; 95 % CI 1·26, 1·88). This study suggests that vitamin D levels are significantly associated with NAFLD and that vitamin D acts as an independent factor for NAFLD prevalence, particularly in males in East China. Vitamin D interventional treatment might be a new target for controlling NAFLD; elucidating the mechanism requires further research.

Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

BackgroundThere is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet.MethodsFemale Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured.ResultsCompared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups.ConclusionsAndronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

Blood lead level and its association with body mass index and obesity in China - Results from SPECT-China study

We aimed to report environmental and blood lead level (BLL) in China, and investigate the relationship of BLL with body mass index (BMI) and obesity. 5558 subjects were enrolled from 16 sites in China. BLL was measured by atomic absorption spectrometry. Obesity was defined as BMI ≥ 30 kg/m2. Median (interquartile range) of BLL was 44.00 μg/L (29.00–62.16) for men and 37.79 μg/L (25.13–54.35) for women, about twice higher than in U.S. population. Subjects in rural and high-economic-status areas had significantly greater BLL (P < 0.001). However, in these areas, the lead levels in drinking water, river water and rice were comparable to or significantly lower than those in urban and low-economic-status areas. After adjustment for age, urbanization, economic status and metabolic factors, BLL was independently associated with BMI in women (P for trend < 0.001), but not in men. In fully adjusted model, increased quartiles of BLL were associated with significantly increased odds ratios of obesity (P for trend < 0.01) in women. In conclusion, BLLs in Chinese adults were much higher than in developed countries. There was a sex-specific association between BLL and BMI. Elevated BLL does not appear to be associated with lead levels in drinking water or rice, suggesting some other exposure source.

Visceral fat dysfunction is positively associated with hypogonadism in Chinese men.

Visceral adiposity index (VAI) well mirrors visceral fat dysfunction. No study explored the association between low androgen and VAI. We aimed to determine whether VAI was associated with hypogonadism and sex hormones, and also whether it better predicted hypogonadism than other obesity indices. Our data were collected from 16 sites in East China. 2,759 men were enrolled. Hypogonadism was defined as total testosterone < 11.3 nmol/L. VAI was calculated in male: (waist circumference/(39.68 + (1.88 × BMI))) × (triglycerides/1.03) × (1.31/HDL). 484 (17.5%) hypogonadal men had significantly higher VAI. After adjusting for age, smoking, neck and hip circumference, diabetes and hypertension, VAI was inversely associated with total testosterone, estradiol and SHBG (P < 0.01). Higher quartiles of VAI were associated with significantly increasing odds of hypogonadism (P for trend < 0.01). The fully adjusted odds ratio was 5.88 (95 CI% 4.09, 8.46) for the highest quartile compared with the lowest quartile of VAI. Among all the indices investigated, VAI showed the largest area under the curve (P < 0.001). In conclusion, the VAI was significantly associated with a higher prevalence of hypogonadism in Chinese men. VAI also best predicted hypogonadism among obesity indices (waist, hip and neck circumference, BMI, waist-hip ratio and body adiposity index).

The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P < 0.01) and glycerol (P < 0.01) and GNG (P < 0.001). During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P < 0.01) during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women

PurposeFollicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women.MethodsSPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells.ResultsIn Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells.ConclusionSerum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

Associations of blood lead levels with reproductive hormone levels in men and postmenopausal women: Results from the SPECT-China Study

We examined whether blood lead levels (BLLs) were associated with reproductive hormone levels in a cross-sectional study using data from the SPECT-China study. We selected 2286 men and 1571 postmenopausal women without hormone replacement therapy. BLLs, blood cadmium, total testosterone (TT), oestradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin(SHBG) levels were measured. The results showed that median values (interquartile range) of BLLs were 44.00 μg/L (29.00–62.30) for men and 41.00 μg/L (27.00–59.81) for postmenopausal women. In linear regression, after adjusting for age, current smoking status, body mass index, systolic blood pressure, diabetes and blood cadmium level, TT (P for trend = 0.001) and SHBG (P for trend < 0.001) levels were still positively associated with BLLs in men. Meanwhile, significant positive associations were found for BLLs with SHBG (P for trend = 0.002), FSH (P for trend = 0.001) and LH (P for trend = 0.026) levels in postmenopausal women. Additionally, the association between BLL and SHBG was modified by dysglycaemia (P for interaction = 0.03) in postmenopausal women. In conclusion, BLLs were associated with reproductive hormone levels in the general population of Chinese men and postmenopausal women, which may have important implications for human health. Concerted efforts to reduce adult lead exposure are warranted.

Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats

Objective: To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis. Methods: Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing. Results: Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus. Conclusion: Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis.

Acute effects of different glycemic index diets on serum motilin, orexin and neuropeptide Y concentrations in healthy individuals

AIM To determine whether different glycemic index (GI) diets have different effects on the acute secretion of motilin, orexin and neuropeptide Y (NPY), regulators of food intake, energy homeostasis and glucose metabolism. METHODS Fifty healthy volunteers were randomly assigned to two groups and were fed an isocaloric breakfast (464 kcal) containing high GI (HGI; GI=90) or low GI (LGI; GI=47) components. Serum motilin, orexin, and NPY concentrations were measured before (0 h) and 2h after the meal. RESULTS The concentrations of motilin, orexin-A, NPY, C-peptide, and blood glucose at 0 h were similar in both groups of subjects. However, 2 h after breakfast, the serum motilin, NPY, C-peptide, and blood glucose concentrations were increased and orexin-A concentrations were decreased in both groups. The percentage changes from 0 to 2 h [(2-h value-0-h value)/baseline×100)] in motilin (27.72±2.46% vs. 20.95±2.06%, p=0.04) and orexin-A (9.15±2.06% vs. 3.49±1.67%, p=0.038) concentrations were significantly higher in the LGI group than in the HGI group. By contrast, the percentage changes in NPY (53.7±9.73% vs. 28.1±5.2%, p=0.026) and blood glucose (12.3±3.78% vs. 1.77±2.52%, p=0.025) concentrations were significantly greater in the HGI group than in the LGI group. Although C-peptide concentrations increased significantly after breakfast in both groups, the magnitude of the increase was similar (132.69±25.15% vs. 139.98±27.29%, p=0.845). Motilin and NPY concentrations were moderately positive correlated (r=0.410, p=0.042), while orexin-A and NPY concentrations were negatively correlated (r=-0.429, p=0.033) at 2h in the LGI group. CONCLUSIONS A breakfast with a LGI reduced the secretion of orexin-A but significantly stimulated motilin secretion, without marked effects on the secretion of NPY. Therefore, consumption of a LGI diet may help to regulate food intake and energy expenditure in healthy individuals based on the changes in these hormones.

Effects of exenatide therapy on insulin resistance in the skeletal muscles of high-fat diet and low-dose streptozotocin-induced diabetic rats

Abstract Purpose: The glucagon-like peptide (GLP)-1 agonist exenatide shows the same multiple effects on glucose homeostasis as native GLP-1, which can reduce blood glucose levels in individuals with type-2 diabetes mellitus (T2DM). However, its underlying action mechanism on glucose metabolism in the skeletal muscle of T2DM cases is unknown. We investigated the effects and action mechanisms of exenatide on insulin resistance (IR) in the skeletal muscle of high-fat diet and low-dose streptozotocin-induced T2DM rats. Methods: Four groups of Sprague–Dawley rats were studied: non-T2DM (control, C); non-T2DM + exenatide (C + E); T2DM (D); and T2DM + exenatide (D + E). After eight weeks, isotope-tracer methodology was applied to measure the total rate of appearance (Ra) of glucose and glucose infusion rate (GIR) using a hyperinsulinemic–euglycemic clamp with 3-3H-glucose infusion. Glucose uptake in gastrocnemius muscles was determined by measuring 2-deoxy-D-14C-glucose radioactivity. Simultaneously, ultrastructural changes in the cells of gastrocnemius muscles were studied. Results: In the D + E group, body weight and levels of fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein and insulin were decreased significantly (p < 0.01) compared with the D group. The Ra of glucose (94.70 ± 13.46 versus 121.07 ± 16.55 μmol/kg/min) was decreased (p < 0.01), whereas the exogenous GIR (144.68 ± 11.03 versus 114.50 ± 9.40 μmol/kg/min) and glucose uptake in muscle (0.24 ± 0.02 versus 0.17 ± 0.02 μmol/g/min) were increased markedly (p < 0.01). Ultrastructural observations revealed that exenatide attenuated the effect of swollen mitochondrial and endoplasmic reticulum within the cells of the skeletal muscle of T2DM rats. Conclusions: These data suggest that exenatide can significantly improve insulin sensitivity in skeletal muscle by increasing glucose uptake in T2DM rats.