1H-NMR-based metabolomics reveals the preventive effect of Enteromorpha prolifera polysaccharides on diabetes in Zucker diabetic fatty rats.

The primary objective of this investigation was to explore the beneficial impacts of Enteromorpha prolifera polysaccharide (EP) on dysglycemia in Zucker diabetic fatty (ZDF) rats, while also shedding light on its potential mechanism using 1H-NMR-based metabolomics. The results demonstrated a noteworthy reduction in fasting blood glucose (FBG, 46.3%), fasting insulin (50.17%), glycosylated hemoglobin A1c (HbA1c, 44.1%), and homeostatic model assessment of insulin resistance (HOMA-IR, 59.75%) following EP administration, while the insulin sensitivity index (ISI, 19.6%) and homeostatic model assessment of ß-cell function (HOMA-ß, 2.5-fold) were significantly increased. These findings indicate that EP enhances ß-cell function, increases insulin sensitivity, and improves insulin resistance caused by diabetes. Moreover, EP significantly reduced serum lipid levels, suggesting improvement of dyslipidemia. Through the analysis of serum metabolomics, 17 metabolites were found to be altered in diabetic rats, 14 of which were upregulated and 3 of which were downregulated. Notably, the administration of EP successfully reversed the abnormal levels of 9 out of the 17 metabolites. Pathway analysis further revealed that EP treatment partially restored metabolic dysfunction, with notable effects observed in valine, leucine, and isoleucine metabolism; aminoacyl-transfer RNA (tRNA) biosynthesis; and ketone body metabolism. These findings collectively indicate the potential therapeutic efficacy of EP in preventing glycemic abnormalities and improving insulin resistance. Thus, EP holds promise as a valuable treatment option for individuals with diabetes.

Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling.

Dysfunction of protein trafficking has been intensively associated with neurological diseases, including neurodegeneration, but whether and how protein transport contributes to oligodendrocyte (OL) maturation and myelin repair in white matter injury remains unclear. ER-to-Golgi trafficking of newly synthesized proteins is mediated by coat protein complex II (COPII). Here, we demonstrate that the COPII component Sec13 was essential for OL differentiation and postnatal myelination. Ablation of Sec13 in the OL lineage prevented OPC differentiation and inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), while improving protein trafficking by tauroursodeoxycholic acid (TUDCA) or ectopic expression of COPII components accelerated myelination. COPII components were upregulated in OL lineage cells after demyelinating injury. Loss of Sec13 altered the secretome of OLs and inhibited the secretion of pleiotrophin (PTN), which was found to function as an autocrine factor to promote OL differentiation and myelin repair. These data suggest that Sec13-dependent protein transport is essential for OL differentiation and that Sec13-mediated PTN autocrine signaling is required for proper myelination and remyelination.

Nucleoporin Seh1 Interacts with Olig2/Brd7 to Promote Oligodendrocyte Differentiation and Myelination.

Nucleoporins (Nups) are involved in neural development, and alterations in Nup genes are linked to human neurological diseases. However, physiological functions of specific Nups and the underlying mechanisms involved in these processes remain elusive. Here, we show that tissue-specific depletion of the nucleoporin Seh1 causes dramatic myelination defects in the CNS. Although proliferation is not altered in Seh1-deficient oligodendrocyte progenitor cells (OPCs), they fail to differentiate into mature oligodendrocytes, which impairs myelin production and remyelination after demyelinating injury. Genome-wide analyses show that Seh1 regulates a core myelinogenic regulatory network and establishes an accessible chromatin landscape. Mechanistically, Seh1 regulates OPCs differentiation by assembling Olig2 and Brd7 into a transcription complex at nuclear periphery. Together, our results reveal that Seh1 is required for oligodendrocyte differentiation and myelination by promoting assembly of an Olig2-dependent transcription complex and define a nucleoporin as a key player in the CNS.