Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Abstract
Purpose. This study aimed to investigate the
role of cathepsin B dependent autophagy induced by
chronic aerobic exercise on a high-fat diet (HFD)-
induced nonalcoholic steatohepatitis (NASH) in rats.
Methods. Healthy female (Sprague-Dawley) SD rats (8-
10 weeks old; 180g-200g; n=6 per group) were divided
into: (1) control group; (2) HFD group; (3) Exercise
group; (4) HFD + exercise group. Rats were fed with a
normal chow or an HFD for 12 weeks. Rats with
exercise ran on a rotarod for 30 min per day from weeks
9-12. Results. Exercise training significantly (1)
upregulated the levels of autophagy markers Beclin1,
ATG5 and LC3II partly through inhibiting the p-
AKT/mTOR pathway; (2) ameliorated HFD-mediated
accumulation of fat mass by upregulating β-oxidation
regulator PPAR-α and downregulating fatty acid
synthesis marker SREBP-1c via lipophagy; (3)
diminished the HFD-induced hepatic pro-inflammatory
mediators TNF-α and IL-1β via NF-κB inactivation; (4)
decreased the NASH-induced hepatic apoptotic marker
caspase-3 activation caused by the upstream oxidative
stress and by cytochrome P450 2E1 (CYP2E1); (5)
mitigated the HFD-mediated lysosomal membrane
permeabilisation and cathepsin B release partly via the
reduction of reactive oxygen species (ROS).
Conclusions. Chronic aerobic exercise reduces oxidative
stress/ROS and ROS may cause lysosomal membrane
destabilisation and disrupts the autophagic process. The
beneficial effect of chronic exercise may further inhibit
the process of lysosome membrane permeabilisation and
facilitate lysosome fusion with autophagosomes to
trigger autophagy. This process may possibly contribute
to the inhibition of cathepsin B released into cytosol
which further reduces inflammation and mitochondrial-
dependent apoptosis