Biology subjects

Wu, J.-C.

Publications and source records attributed to Wu, J.-C..

3 recordsLinked to original sources

bioRxiv2024

The ameliorative effect of C-Kit pos hepatic endothelial Mertk deficiency on nonalcoholic steatohepatitis

Recently, Mer tyrosine kinase (Mertk) and KIT proto-oncogene (C-Kit) were reported play a role in liver sinusoidal endothelial cells (LSECs) in patients with nonalcoholic steatohepatitis (NASH). In this study, lower levels of C-Kit and higher levels of Mertk/p-Mertk were confirmed in steatotic LSECs and in the livers of patients and mice with NASH. C-Kit was suggested to negatively regulate Mertk signaling in steatotic LSECs. The steatotic LSECs in which Mertk was knocked down displayed high fenestration and reduced expression of procapillarized CD31/VN; showed antiangiogenic features and decreased expression of proangiogenic VEGF/ERK1/2; and exhibited intact mitophagy and upregulation of the Pink1/Parkin pathway. Bone marrow transplantation (BMT) of C-Kitpos-BMCssh-Mertk to MCD mice could equivalently protect endothelial functions. Steatotic hepatocytes (HCs) or hepatic stellate cells (HSCs) cocultured with LSECssh-Mertk exhibited diminished lipid deposition; decreased expression of prolipogenic LXR/SREBP-1c, proinflammatory TNF-/IL-6 and profibrotic -SMA/ColI; and increased expression of prolipolytic FXR/ADPN. Similarly, the BMT of C-Kitpos-BMCssh-Mertk to MCD mice ameliorated NASH. C-Kitpos-LSECs that underwent Mertk cleavage were found to limit NASH progression. Therefore, Mertk deficiency should be a novel therapeutic agent for restoring LSECs in patients with NASH.

molecular biology↗

bioRxiv2024

Dietary bacteria controls C. elegans lipid metabolism through pathways converging at phosphatidylcholine

Dietary factors play a pivotal role in regulating metabolism in both health and disease. Lipid metabolism is particularly important for organismal health and longevity. However, the mechanisms by which dietary factors influence lipid metabolism remain poorly understood. Here, using the nematode C. elegans as a model system, we investigated the influence of distinct bacterial diets on fat metabolism. We found that dietary vitamin B12 activates the S-adenosyl methionine (SAM) and phosphatidylcholine (PC) biosynthetic pathways. This activation leads to elevated levels of PC, which in turn suppresses the expression of the gene fat-7 and modulates lipid droplet dynamics through the regulatory proteins SBP-1/SREBP1 and SEIP-1/SEIPIN, respectively. Additionally, we identified a feedback loop involving SBP-1-mediated regulation of acid sphingomyelinase ASM-3, which enhances the production of phospho-choline and further stimulates PC synthesis. Our localization studies further suggest that ASM-3 may act as a signaling mediator between the intestine and coelomocytes, coordinating their roles in vitamin B12-mediated fat regulation. Overall, our findings shed new light on the complex interplay between diet and metabolic regulation, with a particular emphasis on the central role of phosphatidylcholine. HighlightsO_LIAnimals govern PC level to regulate lipid homeostasis in response to diets C_LIO_LIB12 regulates SAM-PC axis to affect lipogenic genes expression and LD biogenesis C_LIO_LICoelomocytes regulate diets-induced lipid homeostasis through asm-3 C_LIO_LIasm-3 constructs a positive feedback loop to participate in PC metabolism C_LI

cell biology↗

bioRxiv2020

Dietary supplementation with PUFAs rescues the eggshell defects caused by seipin mutations in C. elegans

SEIPIN, an ER membrane protein, plays critical roles in lipid droplet (LD) formation and lipid storage. Dysfunction of SEIPIN causes a variety of human diseases, including lipodystrophy, neuropathies, and male and female infertility. However, the cellular and molecular mechanisms of SEIPIN in causing these diseases are poorly understood. To address such mechanisms, we investigated the functional roles of R01B10.6 (seip-1), the sole SEIPIN1 ortholog in C. elegans, using CRISPR/Cas9 gene editing, and transcriptional assays. SEIP-1::mScarlet is widely expressed throughout development in C. elegans. Three full gene deletion mutants, generated by CRISPR/Cas9, displayed penetrant embryonic lethality. EM imaging and the visualization of reporter genes revealed that the lipid-rich permeability barrier, the innermost layer of the C. elegans embryonic eggshell, was defective or missing. Intriguingly, depletion of SEIP-1 revealed a perturbed gene expression pattern for fatty acid biosynthesis enzymes, in agreement with the disrupted permeability barrier formation phenotype of the embryos. Lastly, dietary supplementation of PUFAs rescued the embryonic lethality and defective permeability barrier in the deletion mutants. In sum, our study suggests that SEIP-1 may maternally regulate LD biogenesis and maintain lipid homeostasis to orchestrate the formation of the lipid-rich permeability barrier, which is crucial for eggshell formation and embryogenesis.

cell biology↗