Kidney plays an important role in ketogenesis induced by risperidone and voluntary exercise in juvenile female rats.

The positive role of ketone bodies in the treatment for mental disorders has been demonstrated. Ketogenesis can be triggered by not only exercise and diet but also metabolic disorders. This study aimed to explore the role of risperidone and exercise in ketogenesis. Thirty-two juvenile female Sprague Dawley rats were randomly assigned into four groups: Vehicle-Sedentary, Risperidone (0.9 mg/kg; b.i.d)-Sedentary, Vehicle-Exercise (three hours daily access to running wheels) and Risperidone-Exercise groups for four weeks. Exercise-intervention significantly ameliorated the risperidone-induced increase in white adipose mass, fasting plasma triglyceride and insulin levels. Compared to the vehicle-exercise group, the risperidone-exercise group had significantly higher plasma ß-hydroxybutyrate (ß-HB) level, which had a positive correlation with plasma non-esterified fatty acid levels. Risperidone-treatment upregulated expression of ketogenic key enzyme, mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (HMGCS2) in the kidney rather than liver. Exercise-intervention significantly enhanced renal carnitine palmitoyltransferase1A (CPT1A) expression. These results suggested that the kidney plays an important role in ketogenesis associated with risperidone and exercise. Therefore, it is important to monitor the levels of plasma ketone bodies while exercise intervention is utilized to prevent risperidone-induced metabolic disorders in young people.

Exercise intervention for preventing risperidone-induced dyslipidemia and gluco-metabolic disorders in female juvenile rats.

Risperidone use in children and adolescents is associated with the development of metabolic disorders including increased accumulation of body fat, dyslipidemia, and glucose and insulin metabolism dysregulation. As pharmacological interventions are often limited in their ability to treat a range of side-effects, this study aimed to evaluate the effectiveness of daily voluntary exercise intervention to prevent metabolic side-effects induced by risperidone in juveniles. Thirty-two juvenile female Sprague Dawley rats were treated with risperidone (0.9 mg/kg; b.i.d; n = 16) or vehicle (0.3 g cookie dough pellet; n = 16). These rats were then assigned to a sedentary or voluntary exercise intervention (three hours daily access to running wheels) group (n = 8/group) for a period of four weeks. An intra-peritoneal glucose tolerance test was performed after three weeks of risperidone treatment and exercise intervention to assess glucose tolerance. During the exercise intervention, risperidone-treated rats ran significantly less than vehicle-treated rats. Risperidone treatment of sedentary rats resulted in significantly increased white adipose tissue, fasting triglyceride and fasting insulin compared to vehicle-treated sedentary rats. Exercise intervention of risperidone-treated rats prevented significant increases in these metabolic parameters compared to risperidone-treated sedentary rats. These results support voluntary exercise as an effective mitigator of metabolic side-effects associated with risperidone treatment in juvenile rats. Dyslipidemia and dysregulation of glucose and insulin metabolism are significant risk factors for morbidities and mortality later in life, therefore a focus on strategies to mitigate these adverse effects is critical. Our findings support clinical trials in exercise intervention to prevent metabolic disorders associated with antipsychotic medication in children and adolescents.

Effects of green tea polyphenols on trace metals level of rats on food restriction and high-fat diet.

Little evidence showed the interplay between tea and diet in the regulation of trace metal. Here, we examined the effects of green tea polyphenols (GTPs) on the level of trace elements (TEs) in rats on food restriction or high-fat diet. Thirty-six rats (Wistar, male) were randomly divided into 6 groups and fed on standard diet, food restriction and high-fat diet with or without GTPs (200 mg/kg bw/day) supplementation, respectively. Levels of vanadium (V), manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo) and cobalt (Co) in feed, whole blood, femur and urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Blood glucose, total cholesterol (TC), triglycerides (TG), high and low density lipoprotein-cholesterol (LDL-C, HDL-C) in serum were determined. Decreased daily intakes of TEs were observed in rats on food restriction and high-fat diet. Decreased whole blood level of Zn, femur level of Co and increase urinary excretion of Se were observed in rats fed on high-fat diet. GTPs altered the whole blood level of several TEs in rats on food restriction (V, Zn, Co) or high-fat diet (V, Se), respectively, but not in rats fed on standard diet. The level of several TEs in femur and the daily urinary excretion of V and Mo were altered by GTPs in rats on all of the three diets. In addition, rats fed on high-fat diet developed dyslipidemia, which was ameliorated by GTPs. The data indicated that diet status played a role in the effects of GTPs on TEs and lipid metabolism, and trace elements may play a role in the modulation of lipid metabolic disturbances by high-fat diet and GTPs.

Bisphenol A induces proliferative effects on both breast cancer cells and vascular endothelial cells through a shared GPER-dependent pathway in hypoxia.

Based on the breast cancer cells and the vascular endothelial cells are both estrogen-sensitive, we proposed a close reciprocity existed between them in the tumor microenvironment, via shared molecular mechanism affected by environmental endocrine disruptors (EDCs). In this study, bisphenol A (BPA), via triggering G-protein estrogen receptor (GPER), stimulated cell proliferation and migration of bovine vascular endothelial cells (BVECs) and breast cancer cells (SkBr-3 and MDA-MB-231) and enhanced tumor growth in vivo. Moreover, the expression of both hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were up-regulated in a GPER-dependent manner by BPA treatment under hypoxic condition, and the activated GPER induced the HIF-1α expression by competitively binding to caveolin-1 (Cav-1) and facilitating the release of heat shock protein 90 (HSP90). These findings show that in a hypoxic microenvironment, BPA promotes HIF-1α and VEGF expressions through a shared GPER/Cav-1/HSP90 signaling cascade. Our observations provide a probable hypothesis that the effects of BPA on tumor development are copromoting relevant biological responses in both vascular endothelial and breast cancer cells.

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway.

SCOPE: Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs). Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD) in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. METHODS AND RESULTS: Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase 2 (HMGCS2) and sirtuin 3(SIRT3) were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE) level and the acetyl-MnSOD (K122)/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. CONCLUSION: The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (Danio rerio).

Defective lipid metabolism is associated with increased risk of various chronic diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol (RSV), a natural polyphenol, has been shown the potential of ameliorating disregulations of lipid metabolism. The objective of this study was to investigate the effects of feed intake and RSV on lipid metabolism in zebrafish (Danio rerio). The adult males were randomly allocated to 6 groups: control (Con, 8 mg cysts/fish/day), control with 20 µmol/L RSV (Con+RSV), calorie restriction (CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF, 60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment period was 8 weeks. Results showed that CR reduced body length, body weight, and condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and induced protein expression of phosphorylated AMP-activated protein kinase-α (pAMPKα), silent information regulator 2 homolog 1 (Sirt1), and peroxisome proliferator activated receptor gamma coactivator-1α (PGC1α). RSV attenuated CR-induced pAMPKα/AMPKαincreases. RSV increased levels of Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in peroxisome proliferator-activated receptor-γ (PPARγ) protein level. Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule-associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish. In conclusion, these results suggest that 1) CR reduces plasma TG level through activation of the AMPKα-Sirt1- PGC1α pathway; 2) under different dietary stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3) RSV might regulate lipid metabolism through the AMPKα-Sirt1-PPARγ pathway in OF zebrafish.

Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux.

Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR) or dietary polyphenols such as green tea polyphenols (GTPs) can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD), DR, high-fat diet (HFD), and three diets plus 200 mg/kg(bw)/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-ß-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA)-treated human proximal tubular epithelial cells (HK-2), which was ameliorated by epigallocatechin-3-gallate (EGCG). Furthermore, GTPs (or EGCG) elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

[Analysis on dietary patterns and influencing factors among the elderly in Yantai City].

OBJECTIVE: To analyze the dietary patterns and influencing factors among the elderly in Yantai City. METHODS: A total of 2626 old people( ≥60 years old) were recruited from 6 districts in Yantai City, including Zhifu District, Muping District, Haiyang District, Zhaoyuan District, Longkou District and Changdao County by stratified cluster of random sampling and surveyed using general questionnaires and dietary questionnaires, while physical examinations were conducted. Factors analysis was used to identify the dietary patterns. Influencing factors of dietary patterns were analyzed by multivariate logistic regression analysis. RESULTS: Three evident dietary patterns were derived by factors analysis including healthy( 31. 83%), traditional( 45. 63%) and western( 22. 54%) dietary patterns. Non-smoking older men with low-literacy were more likely to follow traditional dietary pattern. The highly educated elderly women were likelyto follow healthy dietary pattern. The elder with a family history of chronic diseases were likely to follow western dietary pattern( P < 0. 001). People who were in family with higher incomes( OR = 1. 53, 95% CI 1. 32- 2. 61) or had family history of diabetes mellitus( OR = 1. 43, 95% CI 1. 21- 1. 98) or family history of coronary heart diseases( OR = 1. 17, 95% CI 1. 08- 1. 84) used western dietary pattern more than healthy dietary pattern. In addition, the elderly male( OR = 2. 87, 95% CI 2. 27- 3. 38) using traditional dietary pattern were more than the elderly female using healthy dietary pattern. CONCLUSION: There are three dietary patterns among the elderly in Yantai City. The main influencing factors include gender, level of education, economic level and a family history of chronic diseases.

[Cross-sectional association between diabetes and obesity among the elderly of different genders in Yantai City].

OBJECTIVE: To explore the cross-sectional association between the incidence of diabetes and obesity among the elderly of different genders, which intends to provide the scientific basis for undertaking glycemia interventions in the early stage to be conducive to the old folks' health status in Yantai City. METHODS: A total of 986 old people (≥ 60 years old) were recruited from 4 districts in Laishan District Yantai City, Penglai City, Qixia City, Haiyang City by stratified cluster of random sampling and surveyed using questionnaires, while the physical examinations and blood glucose tests were conducted. The logistic regression model was used to analyze the cross-sectional association between the incidence of diabetes and obesity among the elderly of different genders in Yantai City. RESULTS: The rates of obesity and abdominal obesity were 10.04% and 60.85% among the old people in Yantai, respectively. The morbidity rate of diabetes was 10.85%. The influencing factors such as age, cultural standard, monthly income, past job category, smoking, drinking were adjusted, the fat old people had 3.121 times as much chance of suffering from obesity as the normal weight ones (OR = 3.121, 95% CI 1.978 - 5.119). And there was a gender difference between diabetes and obesity. The cross-sectional association between the incidence of diabetes and masculine obesity was of statistical significance alone (OR = 3.924, 95% CI 1.561 - 7.174). The elderly with the abdominal obesity 2.398 times as likely to suffer from diabetes as the elderly with the non-abdominal obesity (OR = 2.398, 95% CI 2.123 - 4.412). There was a gender difference between diabetes and abdominal obesity. The cross-sectional association between the incidence of diabetes and masculine abdominal obesity was of statistical significance alone (OR = 2.917, 95% CI 1.249 - 4.019). CONCLUSION: There are gender difference in the relationship between obesity, abdominal obesity and diabetes in the elderly in Yantai. BMI and waist circumference can be used as the predictive indexes of masculine diabetes.

Mitochondrial HMG-CoA synthase partially contributes to antioxidant protection in the kidney of stroke-prone spontaneously hypertensive rats.

OBJECTIVE: Increased oxidative stress plays an important role in cardiovascular diseases including hypertension and stroke. Evidence has indicated that ketone bodies could exert antioxidative effects. We explored the role of renal mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2) expression, a key control site of ketogenesis, in stroke-prone spontaneously hypertensive rats (SHRSPs) and their ancestral hypertensive but stroke-resistant spontaneously hypertensive rats (SHRs). METHODS: Two groups of SHRSPs were fed a standard chow or standard chow supplemented with clofibrate (an agonist of HMGCS2 promoter), respectively, and SHRs fed with a standard chow were used as controls. The renal levels of HMGCS2, Akt, and phosphorylated protein kinase B (Akt) were measured by western blotting. Malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase were detected by assay kits. RESULTS: Compared with SHRs, lower HMGCS2 protein expression, enhanced phosphorylated Akt signal, higher malondialdehyde levels, and higher catalase activity were observed in kidney tissues in SHRSPs (P < 0.05). No differences in superoxide dismutase and glutathione peroxidase activities were observed between SHRSPs and SHRs. Clofibrate treatment significantly upregulated renal HMGCS2 expressions, inhibited phosphorylation of Akt, and decreased malondialdehyde levels and catalase activities in SHRSP kidney tissues (P < 0.05). CONCLUSION: These results demonstrated the difference in HMGCS2 expression and oxidative stress in kidney tissues between SHRSPs and their SHR controls. The enhanced oxidative stress was partly due to the lower HMGCS2 expression regulated possibly by the Akt signaling pathway.

[Effects of carbon source and flooding time on microbial Fe(III) reduction in paddy soils].

Paddy soil samples were collected from six provinces of China, and an anaerobic incubation test was conducted to examine the microbial Fe(III) reduction potential under the conditions of different flooding time and with glucose, pyruvate, lactate, or acetate as the sole carbon source. The results showed that flooding time had significant effects on the eigenvalue of Fe(III) reduction, Vmax, with the order of 20 d > 30 d > 12 d > 1 d > 5 d, which suggested that the difference in the microbial community structure in different flooding periods was the main reason inducing the different potential of Fe(III) reduction. In all test flooding periods, glucose and pyruvate were the superior carbon sources, with the Fe(III) reduction rate being 88.1%-99.9% and 58.0%-97.9%, respectively. When lactate was amended, the Fe(III) reduction rate varied greatly among different paddy soils. For the paddy soils from Hunan and Zhejiang, the Fe(III) reduction rate during flooding period could reach 87.1%-100%; while for other soils, it was 5.0%-49.4% in the first 5 days of flooding and 52.2%-99.9% in 12 days after flooding. When acetate was used as a carbon source, the Fe(III) reduction rate increased with flooding time. Especially in the paddy soil from Zhejiang, the Fe(III) reduction rate changed greatly from 5.3% to 75.8%.

Green tea polyphenols inhibit plasminogen activator inhibitor-1 expression and secretion in endothelial cells.

Compelling epidemiological evidence suggests that the consumption of green tea is associated with beneficial effects in prevention of cardiovascular diseases. Plasminogen activator inhibitor-1 (PAI-1) is known to play a pivotal role in cardiovascular diseases including arteriosclerosis and hypertension. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. To determine the effect and molecular mechanism of green tea polyphenols (GTPs) on the regulation of PAI-1 expression in endothelial cells, bovine aortic endothelial cells were incubated with GTPs, and PAI-1 expressions were measured by western blot and enzyme-linked immunosorbent assay, respectively. GTPs significantly reduced PAI-1 expression and secretion in a time-dependent and dose-dependent manner. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin markedly reversed GTPs repression of PAI-1 expression. In addition, the GTP-induced inhibitory effect was associated with an increased of activation of the protein kinase Akt. These results suggest that GTPs inhibit PAI-1 expression and its release from endothelial cells through the PI3K/Akt pathway, which may contribute to cardiovascular protection.

Green tea polyphenols down-regulate caveolin-1 expression via ERK1/2 and p38MAPK in endothelial cells.

Caveolin-1 (Cav-1), a negative regulator of endothelial nitric oxide synthase (eNOS), influences various aspects of the cardiovascular functions. We had reported that a high-fat diet up-regulated aortic Cav-1 expressions in rats. In this study, we investigated the effects of green tea polyphenols (GTPs) on endothelial Cav-1 expression and phosphorylation in vitro. Bovine aortic endothelial cells (BAECs) were treated with 4 microg/ml GTPs for 0, 4, 8, 12, 16 and 24 h, and with 0, 0.04, 0.4, 4 and 40 microg/ml GTPs for 16 h, respectively. Cav-1 protein and mRNA were detected using Western blot and reverse transcriptase polymerase chain reaction. Cav-1 protein expression was down-regulated after treatment of BAECs with 4 microg/ml GTPs for 12, 16 and 24 h. And decrease in the level of Cav-1 mRNA was observed after GTP treatment for 4 and 8 h. GTPs (0.04-4 microg/ml) down-regulate Cav-1 protein expressions and mRNA levels dose dependently. PD98059, an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2), up-regulated Cav-1 expression in BAECs alone and abolished the down-regulation effects of GTPs in BAECs while pretreatment with it. Inhibition of p38 mitogen-activated protein kinase (p38MAPK) with SB203580, which down-regulates Cav-1 expression in BAECs alone, deteriorated the Cav-1 down-regulating effects by GTPs. In addition to the effects on expression of Cav-1, GTP treatment inhibited phosphorylation of Cav-1 [tyrosine 14 (Tyr14)]. These data indicate that GTPs down-regulate gene expression of Cav-1 time- and dose- dependently via activating ERK1/2 and inhibiting p38MAPK signaling.