Skeletal muscle atrophy is exacerbated by steatotic and fibrotic liver‐derived TNF‐α in senescence‐accelerated mice

Abstract

Although liver diseases, including non-alcoholic steatohepatitis (NASH), are associated with skeletal muscle atrophy, the mechanism behind their association has not been fully elucidated. In this study, the effects of aging and NASH on the skeletal muscle and the interaction between the liver and muscle were investigated using a diet-induced NASH model in senescence-accelerated mice (SAM). A total of four groups of SAM and its control mice were fed either an NASH-inducing or control diet. In the SAM/NASH group, the histopathology of NASH and markers of oxidative stress were signi cant. Skeletal muscles were also markedly atrophied. The expression of the ubiquitin ligase Murf1 in the muscle was signi cantly increased with muscle atrophy, while that of Tnfa was not signi cantly different. In contrast, the hepatic Tnfa expression and serum TNF-α levels were signi cantly increased in the SAM/NASH group. These results suggest that liver-derived TNF-α might promote muscle atrophy associated with steatohepatitis and aging through Murf-1. The metabolomic analysis of skeletal muscle indicated higher spermidine and lower tryptophan levels in the NASH-diet group. The ndings of this study revealed an aspect of liver-muscle interaction, which might be important in developing treatments for sarcopenia associated with liver diseases.

Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential

“…This might be a result of upregulation of systemic inflammation (Lu et al, 2022). After all, systemic inflammation would induce a senescence‐like syndrome (Shirakami et al, 2023). This issue is worth further exploration.…”

A Novel Mouse Model of Intrahepatic Cholangiocarcinoma Induced by Azoxymethane

“…A qRT-PCR analysis was performed using the LightCycler 96 System (Roche Diagnostics, Indianapolis, IN, USA) with LightCycler 480 SYBR Green I Master Mix (Roche Diagnostics). The specific primers used to amplify Ccl2, Fgfr2, Il6, Krt19, Tnfa, and 18s genes were obtained from previous reports [14,44,45] or designed using Primer-BLAST (https://www.ncbi.nlm.nih.gov/tools/primer-blast/, accessed on 1 March 2023) as follows: Ccl2, forward 5 -CCA TCA GTC CTC AGG TAT TGG-3 , reverse 5 -CTT CCG GAC GTG AAT CTT CT-3 ; Fgfr2, forward 5 -CAA ACA CTC GTC CCC TGT CT-3 , reverse 5 -GGA TGT TCG TGG GAG ATG TT-3 ; Il6, forward 5 -CCG GAG AGG AGA CTT CAC AGA G-3 , reverse 5 -CTG CAA GTG CAT CAT CGT TGT T-3 ; Krt19 forward 5 -CCA TCT GAG CTA CCA GCG AG-3 , reverse 5 -GTC GAG GGA GGG GTT AGA GT-3 ; Tnfa, forward 5 -TGG CCC AGA CCC TCA CAC TCA G-3 , reverse 5 -ACC CAT CGG CTG GCA CCA CT-3 ; and 18s, forward 5 -CCA TCC AAT CGG TAG TAG CG-3 , reverse 5 -GTA ACC CGT TGA ACC CCA TT-3 . The expression levels of these genes were normalized to those of 18s.…”