152589 - Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity.pdf (2.54 MB)
Download fileCentral s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity
journal contribution
posted on 2023-05-21, 12:25 authored by Rodriguez, M, Pintado, C, Molto, E, Gallardo, N, Carmen Fernandez-MartosCarmen Fernandez-Martos, Lopez, V, Andres, A, Arribas, CS-resistin, a non-secretable resistin isoform, acts as an intracrine factor that regulates adipocyte maduration, inflammatory and insulin response in 3T3-L1 cells. However, its intracellular function in vivo is still unknown. In this study, we analyze the central role of s-resistin, decreasing its hypothalamic expression using an intracerebroventricular injection of lentiviral RNAi. The data present herein support an improvement in the hypothalamic leptin and insulin signaling pathway upon s-resistin downregulation. Furthermore, hypothalamic levels of pro-inflammatory markers decrease, meanwhile those of the anti-inflammatory cytokine IL-10 increases. Interestingly, peripheral NEFA decreases alike circulating leptin and resistin levels. These data demonstrate that hypothalamic s-resistin controls fuel mobilization and adipokines secretion. Importantly, central s-resistin downregulation improves systemic insulin sensitivity, as demonstrated after an IPGTT. Interestingly, our data also indicate that s-resistin downregulation could improve hypothalamic inflammation in aged Wistar rats. Altogether, our findings suggest that hypothalamic s-resistin seems to be a key regulator of the brain-fat axis which links inflammation with metabolic homeostasis.
History
Publication title
Scientific ReportsVolume
8Article number
3921Number
3921Pagination
1-13ISSN
2045-2322Department/School
Wicking Dementia Research Education CentrePublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2018 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/Repository Status
- Open