A genome-wide association study identifies FSHR rs2300441 associated with follicle-stimulating hormone levels

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play critical roles in female reproduction, while the underlying genetic basis is poorly understood. Genome-wide association studies (GWASs) of FSH and LH levels were conducted in 2590 Chinese females including 1882 polycystic ovary syndrome (PCOS) cases and 708 controls. GWAS for FSH level identified multiple variants at FSHR showing genome-wide significance with the top variant (rs2300441) located in the intron of FSHR. The A allele of rs2300441 led to a reduced level of FSH in the PCOS group (β = −.43, P = 6.70 × 10−14) as well as in the control group (β = −.35, P = 6.52 × 10−4). In the combined sample, this association was enhanced after adjusting for the PCOS status (before: β = −.38, P = 1.77 × 10−13; after: β = −.42, P = 3.33 × 10−16), suggesting the genetic effect is independent of the PCOS status. The rs2300441 explained sevenfold higher proportion of the FSH variance than the total variance explained by the two previously reported FSHR missense variants (rs2300441 R2 = 1.40% vs rs6166 R2 = 0.17%, rs6165 R2 = 0.03%). GWAS for LH did not identify any genome-wide significant associations. In conclusion, we identified genome-wide significant association between variants in FSHR and circulating FSH first, with the top associated variant rs2300441 might be a primary contributor at the population level

Fatty Acid, Triglyceride, and Kinetic Properties of Milk Fat Fractions Made by the Combination of Dry Fractionation and Short-Path Molecular Distillation.

peer reviewedIn this study, we aimed to detect the physicochemical properties of distilled products (residue and distillate) obtained from anhydrous milk fat (AMF) and its dry fractionation products (liquid and solid fractions at 25°C (25 L and 25 S)). The results showed that the saturated fatty acids and low- and medium-molecular-weight triglycerides were easily accumulated in the distillate, and the percentage of unsaturated fatty acid and high-molecular-weight triglycerides in the residue were higher, and these components in 25 S and 25 L were influenced more significantly than those in the AMF. In addition, the distillate had larger melting ranges in comparison with the distilled substrate, while the melting ranges of residue was smaller. The triglycerides were presented as the mixture crystal forms (α, β', and β crystal) in 25 S, AMF, and their distilling products, and it was transformed gradually to a single form as the increasing of distilling temperature. Moreover, the accumulated pattern of triglycerides was double chain length in 25 S, AMF, and their distilling products. These results provide a new approach to obtain the MF fractions with different properties, and the findings of this study enrich the theoretical basis of MF separation in practical production

Free fatty acid hydrolyzed with lipases and their effects on enzyme-modified cheese flavor

peer reviewed: This study investigated the effects of five lipases on enzyme-modified cheese (EMC) flavor development. Results showed that lipase 30SD contained high hydrolytic activity for short, medium, and long-chain fatty acids within 24 h incubation time, and the highest content of them among different times could reach 47.24, 475.90, 1 563.92 mg/100 g fat, respectively. Lipase DF15 and MER showed moderate capacity to hydrolyze volatile fatty acids, while lipase F3G had a stronger ability to produce long-chain fatty acids. Twenty-seven new volatiles were formed during lipolysis, most of them were acids and esters. Principal component analysis results showed that EMC produced by lipase 30SD for 18 h was similar to the commercial product with a pungent, rancid, and cheddar flavor. EMCs produced by lipase DF15 were significantly distinguished from other products by their high content of ethyl heptanoate, ethyl nonanoate, and ethyl tridecanoate. The findings might be useful for the researchers who focus on lipolysis or EMC product

Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism

Abstract Background 17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown. Methods In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC–MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro. Results sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression. Conclusion These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism

Rheological properties and microstructure of rennet-induced casein micelle/κ-carrageenan composite gels

This study aimed to investigate effects of kappa-carrageenan (κ-carrageenan) concentration and storage temperature on the rheological and texture properties of casein micelle/κ-carrageenan composite gels. The particle size, zeta potential, Fourier transform infrared spectroscopy of the mixture, and microstructure of the composite gels were measured. The movement of κ-carrageenan characteristic bond showed that the casein micelle and κ-carrageenan formed a complex with larger particle size through electrostatic adsorption. The electrostatic repulsion between molecules increased with the increase of κ-carrageenan concentration, which stabilized the mixed system. It was found that both κ-carrageenan concentration and storage conditions affected the gel's rheological properties and microstructure. As the concentration of κ-carrageenan increased, the storage modulus (G′) of the composite gels increased, the rennet coagulation time (RCT) decreased, and the water holding capacity (WHC) increased at 25 °C. Microstructure results showed that a more uniform and denser gel network structure with smaller pore sizes was formed after the addition of κ-carrageenan compared with the control. G′ and RCT were reduced and microscopic phase separation occurred after storage at 4 °C, resulting in a porous structure with large pore sizes. Thus, the addition of κ-carrageenan could enrich the diversity of food gel structure to obtain an ideal gel

Fatty acid, triglyceride, and kinetic properties of milk fat fractions made by the combination of dry fractionation and short-path molecular distillation

ABSTRACT: In this study, we aimed to detect the physicochemical properties of distilled products (residue and distillate) obtained from anhydrous milk fat (AMF) and its dry fractionation products (liquid and solid fractions at 25°C [25 L and 25 S]). The results showed that the saturated fatty acids and low- and medium molecular–weight triglycerides were easily accumulated in the distillate, and the percentage of unsaturated fatty acid and high molecular–weight triglycerides in the residue were higher, and these components in 25 S and 25 L were influenced more significantly than those in the AMF. In addition, the distillate had larger melting ranges in comparison with the distilled substrate, while the melting ranges of residue was smaller. The triglycerides were presented as the mixture crystal forms (α, βʹ, and β crystal) in 25 S, AMF, and their distilling products, and it was transformed gradually to a single form as the increasing of distilling temperature. Moreover, the accumulated pattern of triglycerides was double chain length in 25 S, AMF, and their distilling products. These results provide a new approach to obtain the milk fat fractions with different properties, and the findings of this study enrich the theoretical basis of milk fat separation in practical production

Allele comparison of rs9939609 in GWAS and replication study.

<p>GWAS = genome-wide association study. In GWAS study, PCOS: control = 741∶704. In replication study, PCOS: control = 2858∶2378. MAF = minor allele frequency. ORs = Odds Ratios. 95% CI = confidence interval. P adj, adjusted P value by BMI and age in logistic regression. P meta, meta-analysis of GWAS and replication study by PLINK.</p

Basic clinical characteristics comparisons between PCOS and Control subjects.

<p>SD = standard error. WHR = wasit-hip ratio. FSH = follicle-stimulating hormone. LH = luteinizing hormone. T = testosterone. P adj, adjusted P value by age and BMI in logistic regression.</p