RESUMEN
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle-stimulating hormone. Though POI affects many aspects of women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch-chain amino acid (BCAA) insufficiency-related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency-induced POI is associated with abnormal activation of the ceramide-reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS-induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
Asunto(s)
Menopausia Prematura , Insuficiencia Ovárica Primaria , Humanos , Femenino , Ratones , Animales , Especies Reactivas de Oxígeno , Aminoácidos , Ratones Endogámicos C57BL , Insuficiencia Ovárica Primaria/inducido químicamente , Insuficiencia Ovárica Primaria/patología , Insuficiencia Ovárica Primaria/terapiaRESUMEN
Low water solubility strictly limits the potential applications of plant or animal proteins such as rice proteins (RPs) and cod proteins (CPs). In this study, nanoscale hydrophilic colloidal co-assemblies (80 ~ 150 nm) with excellent water solubility were prepared by hydrating RPs and CPs at pH 12 combined with neutralization. The solubility of RPs was boosted to over 90% (w/v), while most of the subunits in CPs became fully soluble. Structural analysis revealed that RPs and CPs non-covalently reacted, which triggered sheet-helix transitions and formed a compact core of RPs coated by a layer of CPs. Both proteins exposed significant hydrophilic motifs and buried hydrophobic moieties, contributing to the high water-dispersibility of their co-assemblies. Moreover, the co-assembled proteins acquired leveraged amino acid compositions between RPs and CPs. This study will enrich the processing technology of protein components, customizing their structural and nutritional characteristics.