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

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journal contribution
posted on 2024-11-21, 01:05 authored by M Rodriguez, C Pintado, E Molto, N Gallardo, Carmen Fernandez-MartosCarmen Fernandez-Martos, V Lopez, A Andres, C Arribas
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

Issue

1

Article number

3921

Number

3921

Pagination

1-13

ISSN

2045-2322

Department/School

Wicking Dementia Research Education Centre

Publisher

Nature Publishing Group

Publication status

  • Published

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/

Socio-economic Objectives

200199 Clinical health not elsewhere classified