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Upregulation of Anti-Oxidative Stress Response Improves Metabolic Changes in L-Selectin-Deficient Mice but Does Not Prevent NAFLD Progression or Fecal Microbiota Shifts.

Authors :
Eswaran, Sreepradha
Babbar, Anshu
Drescher, Hannah K.
Hitch, Thomas C. A.
Clavel, Thomas
Muschaweck, Moritz
Ritz, Thomas
Kroy, Daniela C.
Trautwein, Christian
Wagner, Norbert
Schippers, Angela
Source :
International Journal of Molecular Sciences; Jul2021, Vol. 22 Issue 14, p7314-7314, 1p
Publication Year :
2021

Abstract

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a growing global health problem. NAFLD progression involves a complex interplay of imbalanced inflammatory cell populations and inflammatory signals such as reactive oxygen species and cytokines. These signals can derive from the liver itself but also from adipose tissue or be mediated via changes in the gut microbiome. We analyzed the effects of a simultaneous migration blockade caused by L-selectin-deficiency and an enhancement of the anti-oxidative stress response triggered by hepatocytic Kelch-like ECH-associated protein 1 (Keap1) deletion on NAFLD progression. (2) Methods: L-selectin-deficient mice (Lsel<superscript>−/−</superscript>Keap1<superscript>flx/flx</superscript>) and littermates with selective hepatic Keap1 deletion (Lsel<superscript>−/−</superscript>Keap1<superscript>Δhepa</superscript>) were compared in a 24-week Western-style diet (WD) model. (3) Results: Lsel<superscript>−/−</superscript>Keap1<superscript>Δhepa</superscript> mice exhibited increased expression of erythroid 2-related factor 2 (Nrf2) target genes in the liver, decreased body weight, reduced epidydimal white adipose tissue with decreased immune cell frequencies, and improved glucose response when compared to their Lsel<superscript>−/−</superscript>Keap1<superscript>flx/flx</superscript> littermates. Although WD feeding caused drastic changes in fecal microbiota profiles with decreased microbial diversity, no genotype-dependent shifts were observed. (4) Conclusions: Upregulation of the anti-oxidative stress response improves metabolic changes in L-selectin-deficient mice but does not prevent NAFLD progression and shifts in the gut microbiota. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
22
Issue :
14
Database :
Complementary Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
151586762
Full Text :
https://doi.org/10.3390/ijms22147314