A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis

Show full item record



Permalink

http://hdl.handle.net/10138/346689

Citation

Lluch , A , Veiga , S R , Latorre , J , Moreno-Navarrete , J M , Bonifaci , N , Nguyen , V D , Zhou , Y , Höring , M , Liebisch , G , Olkkonen , V M , Llobet-Navas , D , Thomas , G , Rodríguez-Barrueco , R , Fernández-Real , J M , Kozma , S C & Ortega , F J 2022 , ' A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis ' , JCI INSIGHT , vol. 7 , no. 14 , e150461 . https://doi.org/10.1172/jci.insight.150461

Title: A compound directed against S6K1 hampers fat mass expansion and mitigates diet-induced hepatosteatosis
Author: Lluch, Aina; Veiga, Sonia R.; Latorre, Jèssica; Moreno-Navarrete, José M.; Bonifaci, Núria; Nguyen, Van Dien; Zhou, You; Höring, Marcus; Liebisch, Gerhard; Olkkonen, Vesa M.; Llobet-Navas, David; Thomas, George; Rodríguez-Barrueco, Ruth; Fernández-Real, José M.; Kozma, Sara C.; Ortega, Francisco J.
Contributor organization: Medicum
Department of Anatomy
University of Helsinki
Date: 2022-07-22
Language: eng
Number of pages: 17
Belongs to series: JCI INSIGHT
ISSN: 2379-3708
DOI: https://doi.org/10.1172/jci.insight.150461
URI: http://hdl.handle.net/10138/346689
Abstract: The ribosomal protein S6 kinase 1 (S6K1) is a relevant effector downstream of the mammalian target of rapamycin complex 1 (mTORC1), best known for its role in the control of lipid homeostasis. Consistent with this, mice lacking the S6k1 gene have a defect in their ability to induce the commitment of fat precursor cells to the adipogenic lineage, which contributes to a significant reduction of fat mass. Here, we assess the therapeutic blockage of S6K1 in diet-induced obese mice challenged with LY2584702 tosylate, a specific oral S6K1 inhibitor initially developed for the treatment of solid tumors. We show that diminished S6K1 activity hampers fat mass expansion and ameliorates dyslipidemia and hepatic steatosis, while modifying transcriptome-wide gene expression programs relevant for adipose and liver function. Accordingly, decreased mTORC1 signaling in fat (but increased in the liver) segregated with defective epithelial-mesenchymal transition and the impaired expression of Cd36 (coding for a fatty acid translocase) and Lgals1 (Galectin 1) in both tissues. All these factors combined align with reduced adipocyte size and improved lipidomic signatures in the liver, while hepatic steatosis and hypertriglyceridemia were improved in treatments lasting either 3 months or 6 weeks.
Description: Publisher Copyright: © 2022, Lluch et al.
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
150461.2_202207 ... 7f913fd3156f593ead4cfd.pdf 3.448Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record