Yi Jiang, Xuan Zhou, Zhenzhen He, Lijie Wei, Shenglan Zhu, Huiting Zhang, Jingyi Zhang, Yuting Chen, Yuanyuan Du, Wencheng Ding, Shaoshuai Wang, Zizhuo Wang, Ling Feng
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引用次数: 0
Abstract
Offspring of women with gestational diabetes mellitus (GDM) face an increased risk of long-term neurodevelopmental abnormalities. This study explores the altered expression of key placental fatty acid transport proteins-FATP2, FATP4, FATP6, FABP4, and FAT/CD36-in GDM patients, and the potential of docosahexaenoic acid (DHA) to mitigate neurodevelopmental risks in offspring by enhancing their expression through activation of peroxisome proliferator-activated receptor γ (PPAR-γ). Our findings demonstrate that placental FATP4 expression is reduced in GDM patients. In HTR8/SVneo cells, PPAR-γ activation upregulated the expression of FATP4, FAT/CD36, and FABP4, while PPAR-γ inhibition only reduced FAT/CD36 expression. DHA treatment led to increased expression of FATP4, FATP/CD36 and FABP4, which was partially reversed by PPAR-γ inhibition. Consistent results were observed in an insulin-resistant cell model. Supplementing GDM mice with exogenous DHA restored placental FATP4 expression and improved offspring social behavior and cognitive function. These results suggest that DHA supplementation during pregnancy could reduce the adverse effects of GDM on placental FATP4 expression and support better neurodevelopmental outcomes in offspring by promoting essential fatty acid transport through the PPAR-γ/FATP4 pathway. This study highlights the therapeutic potential of DHA in improving fetal outcomes in GDM pregnancies.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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