[Effect of epigallocatechin-3-gallate on liver lipid metabolism in rats with intrauterine growth restriction and related mechanism].

OBJECTIVE: To study the effect of epigallocatechin-3-gallate (EGCG) on liver lipid metabolism in rats with intrauterine growth restriction (IUGR) and related mechanism. METHODS: A rat model of IUGR was established by food restriction during entire pregnancy, and then the rats were randomly divided into an IUGR group and an EGCG group (n=8 each). The rats in the EGCG group were fed with water containing EGCG from after weaning to 10 weeks. Eight pup rats born from the pregnant maternal rats without food restriction were used as the control group. At the age of 13 weeks, body weight was measured. Blood and liver tissue samples were collected to measure fasting total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), and liver lipids. Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (adipo-IR) were calculated. Pathological sections of the liver were observed and quantitative real-time PCR was used to measure the mRNA expression of related genes in the liver. RESULTS: At the age of 13 weeks, there was no significant difference in body weight between groups (P=0.067). There were significant differences between groups in FPG, FFA, FINS, HOMA-IR, and adipo-IR (P<0.05). There were no significant differences in the serum levels of TC and TG between groups (P>0.05), while the IUGR group had significantly higher levels of TC and TG in the liver than the EGCG group (P<0.05). Oil red staining showed that the IUGR group had a significant increase in hepatic lipid accumulation, while the EGCG group had certain improvement after EGCG treatment. PCR results suggested that compared with the control group, the IUGR group had significant reductions in the mRNA expression of Ampk and Adipor1 and a significant increase in the mRNA expression of Srebf1 (P<0.05), while EGCG increased the mRNA expression of Ampk and reduced the mRNA expression of Srebf1, with no significant differences in the two indices between the EGCG and control groups (P>0.05). CONCLUSIONS: Early EGCG intervention can down-regulate the de novo synthesis of fatty acids through the Ampk/Srebf1 signaling pathway and reduce hepatic lipid accumulation in IUGR rats by improving insulin resistance of hepatocytes.

Dopamine receptor D2 polymorphism is associated with alleviation of obesity after 8-year follow-up: a retrospective cohort study in obese Chinese children and adolescents.

OBJECTIVE: The aim of this study was to explore the association of dopamine receptor D2 (DRD2) polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up. METHODS: This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical characteristics and DRD2 polymorphisms (including rs1076562, rs2075654, and rs4586205) were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance. RESULTS: One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carriers (68.6% for TC+TT) was higher compared to the major allele homozygote (43.3% for CC). After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carriers for the alleviation of obesity was 3.34 (95% confidence interval (CI): 1.30‒8.58). CONCLUSIONS: The rs2075654 polymorphism of DRD2 is related to long-term obesity alleviation in obese Chinese children and adolescents.

Omega-3 fatty acids as a treatment for non-alcoholic fatty liver disease in children: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The most typical chronic liver disease in children and adolescents is non-alcoholic fatty liver disease (NAFLD). The dietary addition of ω-3 polyunsaturated fatty acids (PUFAs) provides a promising therapy for children with NAFLD due to its convenience and safety; however, several studies suggested contradictory results for PUFA supplementation in children. Hence, we performed a systematic review and meta-analysis to evaluate the effectiveness of PUFA supplementation in children with NAFLD. METHODS: Published randomized controlled trials (RCTs) that evaluated the effectiveness of the dietary addition of PUFA in children with NAFLD were considered. The primary result was the alteration in hepatic steatosis grade on ultrasound after treatment. The secondary outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP) and components of metabolic syndrome. Predefined sensitivity analysis was also performed to explore possible explanations for heterogeneity in the evaluations. RESULTS: In total, 4 studies with 263 subjects were identified. PUFA supplementation was associated with significantly improved hepatic steatosis grade on ultrasound (risk difference: 25%, 95% CI: 12-38%), without heterogeneity (P = 0.27, I2 = 24%). Sensitivity analysis confirmed the robustness of our findings. PUFA supplementation could decrease AST levels after 6 months, but could only reduce ALT levels after 12 months. PUFA did not have a significant effect on most components of metabolic syndrome and the CRP level. CONCLUSION: ω-3 PUFA supplementation can improve liver steatosis and liver functions, and it is a potential food supplementation to treat NAFLD in children.

Relationship between birth weight and total cholesterol concentration in adulthood: A meta-analysis.

BACKGROUND: Although a substantial number of studies have investigated the relationship between birth weight and serum cholesterol later in life, the results vary extensively. The aim of this study was to explore the relationship between birth weight and total cholesterol concentration in adulthood. METHODS: We considered the results of several published observational studies that reported the association between birth weight and total cholesterol concentration in adulthood. The associations were assessed by linear regression coefficients. Summary regression coefficients with 95% confidence intervals (CI) were computed using random-effects models. Subgroup and sensitivity analyses were also conducted to explore possible explanations for heterogeneity among the studies. RESULTS: A total of 20 studies with 26,122 participants were identified. After adjustment for adult body mass index, the summary regression coefficient for an increment in birth weight of 1 kg was -0.09 mmol/L (95% CI: -0.13, -0.05) for men without heterogeneity (I2 = 17.2%) and -0.08 mmol/L (95% CI: -0.13, -0.03) for women with low heterogeneity (I2 = 34.0%). Stratified and sensitivity analyses generally confirmed the robustness of the findings in men. However, subgroup analyses by age indicated that the association of birth weight with total cholesterol was statistically significant only in women aged <50 years. There was no evidence of publication bias in these studies. CONCLUSION: Based on our results, lower birth weight was found to be associated with higher concentrations of total cholesterol in men aged >18 years and in women aged <50 years.

Fish oil improves lipid profile in juvenile rats with intrauterine growth retardation by altering the transcriptional expression of lipid-related hepatic genes.

OBJECTIVE: To determine whether maternal intrauterine undernutrition and post-weaning fish oil intake influence lipid profile in juvenile offspring, and explore the possible mechanisms at transcriptional levels. METHODS: After weaning, 32 control offspring and 24 intrauterine growth retardation (IUGR) offspring were randomly allocated to standard chow or fish oil diet. At 10 weeks, fasting plasma glucose, triglycerides, total cholesterol and expressions of related hepatic genes were examined. RESULTS: IUGR offspring without catch-up growth tended to develop hyperglycemia, dyslipidemia and hepatic steatosis. Down-regulation of CPT-1 and LDLR at transcriptional levels were found in IUGR offspring. Early short-term fish oil intervention reversed these unfavorable changes in juvenile rats with IUGR. The mechanisms might be mediated by decreased expression of ACC-1, increased expression of CPT-1, LDLR and ABCG5. CONCLUSION: These data suggest that IUGR offspring already present lipid abnormality in juvenile stage, and early short-term fish oil consumption is beneficial to prevent these unfavorable changes.

[Effects of asthma and inhaled corticosteroids in children on the final adult height: a systemic review and Meta analysis].

OBJECTIVE: To evaluate the effects of asthma and inhaled corticosteroids (ICS) in children on the final adult height. METHODS: A search was performed to collect studies evaluating the relationship between asthma and ICS in children and the final adult height in PubMed, BCI, EMbase, Web of Science, CNKI and Wanfang databases, then a systemic review and Meta analysis were conducted. RESULTS: Six studies evaluating the relationship between childhood asthma and the final adult height were enrolled. Three of them indicated that the final adult height was not influenced by childhood asthma. Two of them suggested a mild effect, and the effect was correlated with severity of childhood asthma. One of them indicated that a lower final adult height related to childhhod asthma was found only in black females without a high school education. Four studies evaluating the relationship between ICS and the final adult height were included. Compared with the non-ICS treatment group, healthy control group and the target height, ICS treatment had no effects on the final adult height. CONCLUSIONS: Childhood asthma does not or only mildly decrease the final adult height. ICS treatment does not significantly affect the final adult height.

[Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats].

OBJECTIVE: To study the effects of intrauterine growth restriction (IUGR) and high-fat diet on the growth, lipid metabolism, and related hepatic genes in rat offspring. METHODS: The rat model of IUGR was established by food restriction during the entire pregnancy. After weaning, 32 normal rats and 24 offspring rats with IUGR were randomly allocated to standard diet group or high-fat diet group. At the age of 10 weeks, fasting plasma glucose and blood lipid were examined. Additionally, pathological sections for hepatic tissues were observed, and the transcriptional levels of related hepatic genes were measured. RESULTS: At the age of 10 weeks, there was a significant difference in body weight between IUGR rats and normal rats on standard diets, but no significant difference in body weight was observed between the two groups on high-fat diets. Compared with the normal rats, IUGR rats showed increased energy intake and increased levels of fasting plasma glucose, total cholesterol, and triglyceride on both standard and high-fat diets. High-fat diets reduced the concentration of serum triglyceride in both normal rats and IUGR rats. IUGR and high-fat diets aggravated the fat accumulation in the liver. Two-factor analysis of variance showed that at the age of 10 weeks, the expression of genes related to lipid metabolism in the liver, PGC-1α, CPT-1, SREBF-2, HMGR, LDLR and SREBF-1, differed significantly between IUGR and normal rats. Compared with standard diets, high-fat diets increased the expression of PPARα, SREBF-1, SREBF-2, ABCG5, and CYP7A1 in both normal rats and IUGR rats. IUGR and high-fat diets had an interactive effect on LDLR expression. CONCLUSIONS: Hyperlipidemia and fat accumulation in the liver observed in IUGR rats may be related to increased appetite and regulation disorder in genes related to fatty acid oxidation at the transcriptional level. High-fat diets may aggravate fat accumulation in the liver in rats, which may be related to increased expression of genes related to regulation of fatty acid synthesis at the transcriptional level and reduction in secretion of triglyceride.

Serum bisphenol A concentration and premature thelarche in female infants aged 4-month to 2-year.

OBJECTIVES: To estimate the association between serum bisphenol A and premature thelarche in female infants aged 4-mo to 2-y. METHODS: A total of 251 female infants (aged 4 mo to 2 y) with premature thelarche and 33 healthy age-matched control subjects were analyzed. All participants underwent physical examination and serum bisphenol A was measured by ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Serum bisphenol A concentration in the premature thelarche group (3.48 ng/ml, 95%CI: 0.09-140.26) was significantly higher than that in the control group (1.70 ng/ml, 95%CI: 0.06-51.78) (p = 0.039). There was no correlation between age and serum bisphenol A (BPA) level. Univariate logistic regression analysis showed that serum BPA concentration positively associated with premature thelarche, and the effect of BPA fell down as the age grew. CONCLUSIONS: This hospital-based study implied that there is an association between serum BPA concentrations and premature thelarche. Additionally, serum BPA levels were markedly higher in infants aged 4-mo to 2-y-old, raising a concern for public health authorities.

Relationship between glycated haemoglobin and subclinical atherosclerosis in obese children and adolescents.

OBJECTIVE: To explore the relationship between glycated haemoglobin A1C (HbA1C) and subclinical atherosclerosis as assessed by carotid intima-media thickness (cIMT) in Chinese Han obese children and adolescents without diabetes. METHODS: A total of 524 obese children and adolescents without diabetes were analysed. All participants underwent HbA1C measurements, oral glucose tolerance tests and ultrasound measurements of cIMT. The logistic regression models were implemented to evaluate the adjusted OR of HbA1C for increased cIMT. RESULTS: In obese boys, HbA1C was associated with increased cIMT independently of age, measurements of anthropometry, blood pressure, plasma lipid and lipoprotein, fasting plasma glucose, 2 h postchallenge glucose, uric acid and hepatic function. After adjustment for all these risk factors, the OR of increased cIMT for every 1% (11 mmol/mol) increase in HbA1C was 2.702 (95% CI 1.640 to 4.452). However, in girls, the major risk factor independently associated with cIMT was measurement of abdominal obesity instead of HbA1C. CONCLUSIONS: Our research suggests that the adoption of HbA1C as a diagnostic criterion of prediabetes and diabetes in obese boys may help to identify early macrovascular complications.

[Non-high-density-cholesterol as a predictor of non-lipid cardiovascular disease risk factors in obese children].

OBJECTIVE: To investigate the role of non-high density lipoprotein cholesterol (non-HDL-C) in the assessment of cardiovascular disease (CVD) risk factors such as hypertension, pre-diabetes and diabetes in obese children. METHODS: According to the presence of complications (hypertension, pre-diabetes and diabetes), 810 children with central obesity were divided into two groups: one group with complications (n=499) and one group without complications (n=311). One hundred and sixty-four age- and sex-matched children served as the control group. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to analyze the detection of non-lipid CVD risk factors by seven lipid markers. RESULTS: The prevalence rates of hypertension and pre-diabetes were significantly higher in obese children with high non-HDL-C concentrations (≥3.76 mmol/L). After adjusting for waist circumference Z-scores, the area under the ROC curve for non-HDL-C was 0.680 to detect non-lipid CVD risk factors, while the areas for low-density lipoprotein cholesterol, total cholesterol and apoprotein B were 0.659, 0.669 and 0.647 respectively. CONCLUSIONS: Compared with the other lipid markers, non-HDL-C is a better predictor for non-lipid CVD risk factors in obese children. Measurement of non-HDL-C concentations is recommended for obese children.

A novel amine receptor based on the binol scaffold functions as a highly effective chiral shift reagent for carboxylic acids.

A "smart" receptor has been newly synthesized. NMR studies demonstrated that the receptor functions as a chiral shift reagent that is highly effective for determining the enantiomeric purity of a series of carboxylic acids, particularly those that have an α-oxygen atom.

Asymmetric catalysis of Morita-Baylis-Hillman reactions by chiral phosphine Lewis bases bearing multiple phenol groups.

In the Morita-Baylis-Hillman (MBH) reactions of arylaldehydes with methyl vinyl ketone, it was observed that in the presence of a catalytic amount of a chiral phosphine Lewis base (CPLB) bearing multiple phenol groups, such as CPLB1 (10 mol %), the corresponding MBH adducts could be obtained in moderate to good yields with low to moderate ee's (4-45% ee) at ambient temperature (10 degrees C) in THF.

Chiral phosphine lewis bases catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with activated olefins.

In the aza-Baylis-Hillman reaction of N-sulfonated imines (N-arylmethylidene-4-methylbenzenesulfonamides and others) with methyl vinyl ketone, ethyl vinyl ketone, and acrolein, we found that, in the presence of a catalytic amount of chiral phosphine Lewis base such as (R)-2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-ol LB1 (10 mol %) and molecular sieve 4A, the corresponding aza-Baylis-Hillman adducts could be obtained in good yields with good to high ee (70-95% ee) at low temperature (approximately -30 to -20 degrees C) or at room temperature in THF, respectively. In CH2Cl2 upon heating at 40 degrees C, the aza-Baylis-Hillman reaction of N-sulfonated imines with phenyl acrylate or naphthyl acrylate gave the adducts in good to high yields (60-97%) with moderate ee (52-77%). The mechanistic insight has been investigated by 31P and 1H NMR spectroscopic measurements. The key enolate intermediate, which has been stabilized by intramolecular hydrogen bonding, has been observed by 31P and 1H NMR spectroscopy. An effective bifunctional Lewis base and Bronsted acid phosphine Lewis base system has been disclosed in this catalytic, asymmetric aza-Baylis-Hillman reaction.

Chiral phosphine Lewis base catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone and phenyl acrylate.

In the aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone (MVK) promoted by chiral phosphine Lewis base: (R)-2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-ol (10 mol%), the aza-Baylis-Hillman adducts 1 were obtained in good yields with high ee (70-94% ee) at -30 degrees C in THF. In CH2Cl2 upon heating at 40 degrees C, the aza-Baylis-Hillman reaction of N-sulfonated imines with phenyl acrylate gave the adducts 2 in high yields (60-97%) with moderate ee (52-77%).