Min Wan

Phosphatidylethanolamine (PE) biosynthesis is critical for membrane biology and cellular homeostasis. However, its specific role in antiviral innate immunity remains poorly understood. Here, we demonstrate that inhibition of phosphoethanolamine cytidylyltransferase 2 (PCYT2), a key enzyme in PE biosynthesis, promotes TBK1 activation to enhance the antiviral innate immune response. Mechanistically, PCYT2 deficiency leads to the accumulation of diacylglycerol, which activates protein kinase C-δ (PKCδ). We identify PKCδ as a direct kinase for TBK1 and demonstrate that it binds to and phosphorylates TBK1 at Ser716. This Ser716 phosphorylation facilitates the subsequent canonical phosphorylation of TBK1 at Ser172, resulting in hyperactivation of the TBK1–IRF3 axis. Our findings uncover a link between PE metabolism and antiviral innate immunity, suggesting that targeting the PE biosynthesis pathway could be a potential therapeutic strategy against viral infections.

Postbiotics are gaining recognition as effective components in functional aquafeeds. In this study, we assessed the physiological effects of postbiotics derived from Cetobacterium somerae WT-1 on juvenile turbot (Scophthalmus maximus L.), with a focus on growth performance, intestinal health, and disease resistance. Six experimental diets were formulated to include increasing levels of postbiotics (0%, 0.2%, 0.4%, 0.6%, 1%, and 2%), labeled Ctrl, F-2, F-4, F-6, F-10, and F-20, respectively. Juvenile fish with an average initial body weight of 10.48 ± 0.02 g were fed the test diets over an eight-week period. Notably, fish receiving 0.4% (F-4) and 0.6% (F-6) supplementation presented significant improvements in weight gain, higher digestive enzyme activities (lipase and trypsin), and better feed utilization compared with the control. Histological examination and gene expression analysis further revealed strengthened intestinal barrier structures and enhanced intestinal immune responses in the F-4 and F-6 groups. Additionally, supplementation with postbiotics from C. somerae WT-1 clearly reshaped the gut microbiota, characterized by enrichment of Lactobacillus spp. and increased microbial functional pathways related to amino acid metabolism, vitamin biosynthesis, and xenobiotic degradation in the F-6 and F-4 groups. Notably, the F-4 and F-6 groups also exhibited markedly enhanced kidney innate immune responses, with the upregulation of hif-1α, il-1β, tnf-α, and lysozyme, leading to significantly higher survival rates of turbot following Edwardsiella tarda (E. tarda) challenge. Collectively, these findings demonstrate that C. somerae WT-1-derived postbiotics exert beneficial effects on growth, gut health, and disease resistance in turbot, underscoring their strong potential as functional feed additives in aquaculture.

Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1^−/− zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.

Our study has identified that VD influences intestinal uptake and transport of folate in zebrafish while also altering hepatic folate metabolism and storage. Interestingly, the regulatory effects of VD on folate transport and metabolism diminished after the gut flora was interrupted by antibiotic treatment, suggesting that the regulatory effects of VD on folate metabolism in zebrafish are most likely dependent on the intestinal flora.