Hypothalamic Hnscr regulates glucose balance by mediating central inflammation and insulin signal. Issue 1 (30th August 2022)

• Record Type: Journal Article
• Authors: Liu, Ya; Guo, Yi‐Fan; Peng, Hui; Zhou, Hai‐yan; Su, Tian; Yang, Mi; Guo, Qi; Ye, Xiao; Huang, Yan; Jiang, Tie‐Jian
• Is Part Of: Cell proliferation. Volume 56:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-08-30
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13332
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Hypothalamic dysfunction leads to glucose metabolic imbalance; however, the mechanisms still need clarification. Our current study was to explore the role of hypothalamic Hnscr in glucose metabolism. Materials and Methods: Using Hnscr knockout or htNSC‐specific Hnscr overexpression mice, we evaluated the effects of Hnscr on glucose metabolism through GTTs, ITTs, serum indicator measurements, etc. Immunofluorescence staining and Western blotting were performed to test inflammation levels and insulin signalling in hypothalamus. Conditioned medium intervene were used to investigate the effects of htNSCs on neuronal cell line. We also detected the glucose metabolism of mice with htNSCs implantation. Results: Hnscr expression decreased in the hypothalamus after high‐fat diet feed. Hnscr ‐null mice displayed aggravated systematic insulin resistance, while mice with htNSC‐specific Hnscr overexpression had the opposite phenotype. Notably, Hnscr ‐null mice had increased NF‐κB signal in htNSCs, along with enhanced inflammation and damaged insulin signal in neurons located in arcuate nucleus of hypothalamus. The secretions, including sEVs, of Hnscr ‐deficient htNSCs mediated the detrimental effects on the CNS cell line. Locally implantation with Hnscr ‐depleted htNSCs disrupted glucose homeostasis. Conclusions: This study demonstrated that decreased Hnscr in htNSCs led to systematic glucose imbalance through activating NF‐κB signal and dampening insulin signal in hypothalamic neurons. Abstract : We discovered the lncRNA Hnscr participated in the regulation of high fat diet‐induced insulin resistance. Hnscr knockout aggravated diet‐induced insulin resistance. Mechanistically, loss of Hnscr reduced trim56 level, leading to NF‐κB activation in htNSCs. Hnscr ‐deficient htNSCs also contributed to increased inflammation and insulin resistance in neurons finally damaged systematic glucose balance.