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152589 - Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity.pdf (2.54 MB)

Central s-resistin deficiency ameliorates hypothalamic inflammation and increases whole body insulin sensitivity

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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, C
S-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 Reports

Volume

8

Article number

3921

Number

3921

Pagination

1-13

ISSN

2045-2322

Department/School

Wicking Dementia Research Education Centre

Publisher

Nature Publishing Group

Place of publication

United Kingdom

Rights 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

Socio-economic Objectives

Clinical health not elsewhere classified

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