Search Results (3)

Background/Objectives: Sterol regulatory element-binding transcription factor 2 (SREBF2) is a key transcription factor involved in regulating cholesterol homeostasis. However, its role in buffalo mammary gland lipid metabolism remains unclear. Methods: To address this, we isolated and characterized the SREBF2 gene from buffalo mammary glands and performed an in-depth analysis of its molecular characteristics, tissue-specific expression, and functional roles in buffalo mammary epithelial cells (BuMECs). Additionally, we investigated the single nucleotide polymorphisms (SNPs) of SREBF2 in both river and swamp buffalo. Results: The coding sequence (CDS) of buffalo SREBF2 is 3327 bp long and encodes a protein of 1108 amino acid residues. Bioinformatics analysis revealed that the molecular characteristics of buffalo SREBF2 were highly similar across Bovidae species, with collinearity being observed among them. An expression profile analysis revealed that SREBF2 is expressed in all 11 tested tissues of buffalo, with its expression level in the mammary gland being higher during lactation than in the dry period. The knockdown of SREBF2 in BuMECs during lactation led to a significant reduction in the expression of genes involved in triglyceride (TAG) and cholesterol synthesis, including PI3K, AKT, mTOR, SREBF1, PPARG, INSIG1, ACACA, SCD, DGAT1, LPL, CD36, HMGCR, and SQLE. This knockdown led to a 23.53% and 94.56% reduction in TAG and cholesterol levels in BuMECs, respectively. In addition, a total of 22 SNPs were identified in both buffalo types, of which four non-synonymous substitutions (c.301G>C, c.304A>T, c.1240G>A, and c.2944G>A) were found exclusively in the SREBF2 CDS of swamp buffalo, and the assessment revealed that these substitutions had no impact on SREBF2 function. Conclusions: These findings emphasize the critical role of SREBF2 in regulating both triglyceride and cholesterol biosynthesis, providing valuable insights into its functions in buffalo mammary glands. Full article

The SCD is a rate-limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids (MUFAs) in dairy cows; however, its role in the mammary gland of buffalo is not well understood. In this study, we isolated and characterized the complete coding sequence (CDS) of the buffalo SCD gene from mammary gland tissue and investigated its effects on milk fat synthesis using bioinformatics analyses, tissue differential expression detection, and cellular functional experiments. The cloned SCD gene has a CDS length of 1080 bp, encoding a protein of 359 amino acids. This protein is hydrophilic, lacks a signal peptide, and contains four transmembrane domains, including 10 conserved motifs and a Delta9-FADS domain, characteristic of the fatty acid desaturase family involved in unsaturated fatty acid biosynthesis within the endoplasmic reticulum. Molecular characterization revealed that the physicochemical properties, conserved domains, structures, and functions of buffalo SCD are highly similar to those in other Bovidae species. Among the tissues analyzed, SCD expression was highest in the mammary gland during lactation and in the cerebellum during dry-off period. Notably, SCD expression in the mammary gland was significantly higher during lactation compared to the dry-off period. Subcellular localization experiments confirmed that SCD functions in the endoplasmic reticulum of buffalo mammary epithelial cells (BuMECs). Functional overexpression and interference experiments in BuMECs demonstrated that SCD promotes milk fat synthesis by affecting the expression of lipid synthesis-related genes such as ACACA, FASN, and DGAT1, as well as milk fat regulatory genes like SREBFs and PPARG, thereby influencing intracellular triglyceride (TAG) content. Additionally, 18 single-nucleotide polymorphisms (SNPs) were identified in the buffalo SCD gene, with a specific SNP at c.-605, showing potential as molecular markers for improving milk production traits. These findings highlight that the SCD gene is a key gene in buffalo milk fat synthesis, involved in the de novo synthesis of milk fatty acids. Full article

Background: Patients with psychotic disorders who receive atypical antipsychotic drugs often develop metabolic abnormalities. The sterol regulatory element-binding factor 2 (SREBF2) gene and insulin-induced gene (INSIG) have important roles in lipid metabolism. A previous study indicated that risperidone stimulated both lipogenesis and cholesterogenesis through activation of SREBP2 expression and inhibition of INSIG2. The SREBF2 gene and INSIG2 polymorphisms have been reported to be associated with metabolic abnormalities. Objective: To investigate the association of the SREBF2 gene (rs1052717, rs2267439, and rs2267443) and INSIG2 (rs7566605, rs11123469, and rs17587100) polymorphisms and the presence of obesity and dyslipidemia in Thai psychotic disorder patients treated with risperidone. Methods: All 113 psychiatric patients using risperidone were evaluated for their lipid profile and screened for obesity criteria. We genotyped the SREBF2 gene and INSIG2 polymorphisms using TaqMan real-time polymerase chain reaction. Results: None of the studied SREBF2 gene and INSIG2 SNPs were associated with obesity in Thai psychotic disorder patients receiving risperidone. Nonetheless, the SREBF2 rs2267443 (G/A) A-allele carriers were at a higher risk for hypertriglyceridemia, whereas the INSIG2 rs11123469 (T/C) C-allele carriers had a lower risk for hypertriglyceridemia, after being adjusted for clinical characteristics using multiple logistic regression. Conclusions: Our findings suggest that the SREBF2 gene rs2267443 (G/A) and the INSIG2 rs11123469 (T/C) polymorphisms are associated with dyslipidemia in Thai psychotic disorder patients treated with risperidone. Further studies with prospective designs and larger patient groups are needed. Full article