Associations among PRDM16 polymorphisms, environmental exposure factors during mother's pregnancy, and nonsyndromic cleft lip with or without cleft palate / 华西口腔医学杂志

OBJECTIVE@#We aimed to study the association between rs7525173, rs2236518, rs2493264 single nucleotide polymorphism (SNP) in the PRDM16 gene, smoking, alcohol exposures, and nonsyndromic cleft lip with or without cleft palate (NSCL/P).@*METHODS@#A total of 157 case-parent trios were selected, and SNPs were genotyped by using ligase detection reaction (LDR) and direct sequencing methods. Transmission disequilibrium test (TDT) and linkage disequilibrium (LD) tests were con-ducted to analyze the data. A total of 1 710 patients with orofacial clefts and 956 healthy newborns were enrolled in the epidemiological survey. The smoking and drinking exposures of parents during early pregnancy were analyzed.@*RESULTS@#The C allele at rs2236518 was over-transmitted for NSCPO (P<0.05). Statistical differences were observed among three factors, namely, maternal smoking, maternal passive smoking, and maternal drinking (P<0.05).@*CONCLUSIONS@#The rs2236518 at PRDM16 gene, maternal smoking, maternal passive smoking, and maternal drinking were closely related to the occurrence of NSCL/P.

Effects of Aerobic and Resistance Exercises on Morphology and Activity of Brown Adipose Tissues in Rats / 中国运动医学杂志

Objective To compare the effect of aerobic and resistance exercise on brown adipose tissues in rats.Methods Sprague-Dawley rats were randomly assigned to a control(C)group,an aerobic exercise (T) group and a resistance exercise(L)group.The rats of group T performed treadmill exercise 5 days per week for 8 weeks,while those of group L climbed vertical ladders with progressively increased weights once in 3 days for 8 weeks.All rats were weighed before and after the intervention.Then the bilateral interscapular brown adipose tissue was isolated and weighed at 48h after the last exercise.The hematoxylin-eosin staining was used to observe the morphology of adipocytes,and the quantitative real-time PCR and Western blotting were employed to detect the mRNA and protein expression of browning genes [PR-domain-containing 16 (PRDM 16),PPAR gamma coactivator-1α (PGC-1 α) and uncoupling protein 1(UCP1)] respectively.Results After the intervention,the increment of weight of group T and group L were only 52％ and 70％ of group C(P＜0.01 and P＜0.05).The weight of BAT in both group T and L was lower than group C,but without significance(P＞0.05).The average size of lipid droplets in group T decreased significantly(P＜0.01) and slightly in group L(P＞0.05) compared with group C.The PRDM16,PGC-1α and UCP1 mRNA expression of group T was 1.78(P＜0.01),2.2(P＜ 0.01) and 1.3(P＞0.05) times of group C,while that of group L was 1.30(P＞0.05),1.25(P＞0.05) and 1.21(P＞0.05) times of group C.The PRDM16,PGC-1α and UCP1 protein level in group T was 1.46-fold(P＜0.05),1.56-fold(P＞0.05)and 1.20-fold(P＞0.05),while that of group L was 1.08-fold(P＞0.05),0.94-fold(P＞0.05) and 1.20-fold(P＞0.05) of group C.Conclusion Eight weeks of aerobic exercise can significantly make the lipid droplets of adipocyte smaller,increase the differentiation and metabolic activity of BAT,and weakly stimulate BAT thermogenesis.However,8 weeks of resistance exercise has no significant effect on BAT.

Relationship between four SNPs of PRDM16 gene and dyslipidemia and their interaction / 中华内分泌代谢杂志

Objective The aim of this study was to evaluate whether PRDM16 gene polymorphisms were associated with dyslipidemia. Methods The polymorphisms of rs2651899, rs2236518, rs870171, and rs2282198 in PRDM16 gene in 528 participants were genotyped by the method of snapshot or ligase detection reaction. The genotype differences and the allele differences between the case group and the control group were analyzed. Linkage disequilibrium analysis was performed with SHE-sis online software. The interaction between rs2651899, rs2236518, rs870171, rs2282198 and gender, age, BMI were analyzed by MDR software. Results The frequency of allele A in rs2651899 locus was significantly higher in low HDL-C group compared with that in control group[OR(95%CI)=1.32(1.02-1.71), P=0.033]. The frequency of A/C genotype in rs870171 was significantly different between LDL-C abnormal group and control group[OR(95% CI)=1.97(1.01-3.86), P=0.037]. There may be interaction between rs2236518 and sex, which is a risk factor for low HDL-C[Model Ⅱ: OR(95% CI)=1.958(1.366-2.809), P<0.01]. There may be interactions among rs2651899, rs2236518, rs870171, and rs2282198, which seemed to be risk factors for lower HDL-C[Model Ⅳ: OR(95% CI)=3.991(2.707-5.884), P<0.01]. rs870171, rs2282198 may have interaction with age, which is a risk factor for high LDL-C [Model Ⅶ: OR(95%CI)=3.991(2.707-5.884), P<0.01]. Conclusion Allele A of rs2651899 may be a risk factor to low HDL-C. Under the codominant inheritance patterns, genotype A/C of rs870171 may be a risk factor to high LDL-C. In addition, there may be interaction between SNPs with gender and age.

The exploration of the correlation between the risk of obesity and the promoter methylation of PRDM16 gene / 中华内分泌代谢杂志

Objective To explore the association between the CpG methylation level of positive regulatory domain containing 16(PRDM16)gene promoter and obesity or body mass index(BMI). Methods A total of 116 patients(91 female adults and 25 male adults) with abdominal operation in a municipal hospital of Henan province were enrolled in this study and they were divided into two groups:normal weight group(n=50), overweight or obesity group ( n=66 ) . Fasting plasma glucose, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein were measured in peripheral blood. DNA was extracted from white blood cells in peripheral blood and modified by bisulphite. Then the CpG methylation level of PRDM16 gene promoter was detected by mass spectrometry. Finally, all data were analyzed by IBM SPSS Statistics 21. 0 at the 5% level. The essential features and biochemical indexes of research objects between two groups were compared by two independent sample t-test, except chi-square test for gender. The correlation between CpG methylation level of PRDM16 gene and BMI was analyzed by multiple linear regression. Results There were no significant differences ( P>0. 05 ) in the methylation levels of PRDM16 gene's effective CpG sites(including CpG5. 6, CpG8, CpG9, CpG12, CpG13. 14. 15, CpG26. 27, CpG28 and CpG29) between two groups. The methylation level of CpG26. 27 had positive linear relation with BMI in overweight or obesity group with the standardized coefficients of 46. 928(P=0. 015), which means the higher the methylation level is, the higher the BMI would be. Conclusion The CpG26. 27 methylation level of PRDM16 gene promoter region may have relationship with the risk of obesity.

Advances in molecular mechanisms of browning of white adipose tissue / 医学研究生学报

Brown and white adipocytes have different metabolism characteristics.White adipocytes promote the formation and development of atherosclerosis.However, brown adipocytes contribute to the control of atherosclerosis.Brown and white adipocyte phe-notypes can transform mutually.This article will elaborate the pathogenesis of the transformation between brown/white adipocyte pheno-types regulated by transcription factors(such as PPARγ, PRDM16, PGC-1α), co-regulators, hormones, proteins, signal molecules, oxidative stress and miRNAs.

Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics

Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 microM) and partially by quetiapine (30 microM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPbeta, PPARgamma2, UCP-1, PGC-1alpha, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARgamma2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 microM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.