RT Journal Article
SR Electronic
T1 Early but not late exercise training in mice exacerbates hepatic inflammation in early NAFLD
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.28.518192
DO 10.1101/2022.11.28.518192
A1 Artemiy Kovynev
A1 Zhixiong Ying
A1 Joost Lambooij
A1 Bruno Guigas
A1 Patrick C.N. Rensen
A1 Milena Schönke
YR 2022
UL http://biorxiv.org/content/early/2022/11/28/2022.11.28.518192.abstract
AB Exercise effectively prevents obesity-related disorders, but it is unclear whether the beneficial health effects of exercise are restricted to unique circadian windows. Therefore, we aimed to study whether timing of exercise training differentially modulates the development and progression of non-alcoholic fatty liver disease (NAFLD), a disease currently estimated to affect over two billion people worldwide. We endurance-trained high fat-high cholesterol-fed NAFLD-prone male APOE*3-Leiden.CETP mice five times per week for eight weeks either in the early (ZT13) or in the late (ZT22) active phase and assessed the NAFLD score (histology) and hepatic inflammation compared to sedentary mice. Exercise training prevented an increase in body fat mass and fasting plasma glucose as expected, but neither early nor late training affected liver triglyceride or cholesterol content compared to sedentary mice, likely due to a very early stage of hepatic steatosis. In line, hepatic expression of de novo lipogenesis genes (e.g., Fasn, Srebp1c) was similarly downregulated by early and late training. However, exercise had a distinct time-dependent effect on hepatic inflammation, as only early training promoted an influx of pro-inflammtory cells into the liver paired with increased expression of the pro-inflammatory cytokines (e.g. Tnfa, Il1b). This data suggests that the timing of exercise is a critical factor for the effect on cardiometabolic disease development.Competing Interest StatementThe authors have declared no competing interest.