RT Journal Article
T1 Impact of lifestyle interventions targeting physical exercise and caloric intake on cirrhosis regression in rats
A1 Lafoz, Erica
A1 García Martínez, Rita
A1 García Pagan, Juan Carlos
AB In patients, advanced cirrhosis only regresses partially once the etiological agent is withdrawn. Animal models for advanced cirrhosis regression are missing. Lifestyle interventions (LIs) have been shown to improve steatosis, inflammation, fibrosis, and portal pressure (PP) in liver disease. We aimed at characterizing cirrhosis regression after etiological agent removal in experimental models of advanced cirrhosis and to study the impact of different LI on it. Advanced cirrhosis was induced in rats either by carbon tetrachloride (CCl4) or by thioacetamide (TAA) administration. Systemic and hepatic hemodynamics, liver fibrosis, hepatic stellate cell (HSC) activation, hepatic macrophage infiltration, and metabolic profile were evaluated after 48 h, 4 wk or 8 wk of etiological agent removal. The impact of LI consisting in caloric restriction (CR) or moderate endurance exercise (MEE) during the 8-wk regression process was analyzed. The effect of MEE was also evaluated in early cirrhotic and in healthy rats. A significant reduction in portal pressure (PP), liver fibrosis, and HSC activation was observed during regression. However, these parameters remained above those in healthy animals. During regression, animals markedly worsened their metabolic profile. CR although preventing those metabolic disturbances did not further reduce PP, hepatic fibrosis, or HSC activation. MEE also prevented metabolic disturbances, without enhancing, but even attenuating the reduction of PP, hepatic fibrosis, and HSC activation achieved by regression. MEE also worsened hepatic fibrosis in early-TAA cirrhosis and in healthy rats.NEW & NOTEWORTHY We have developed two advanced cirrhosis regression experimental models with persistent relevant fibrosis and portal hypertension and an associated deteriorated metabolism that mimic what happens in patients. LI, despite improving metabolism, did not enhance the regression process in our cirrhotic models. CR did not further reduce PP, hepatic fibrosis, or HSC activation. MEE exhibited a profibrogenic effect in the liver blunting cirrhosis regression. One of the potential explanations of this worsening could be ammonia accumulation.
PB American Physiological Society
SN 0193-1857
YR 2021
FD 2021-09-20
LK https://hdl.handle.net/20.500.14352/131076
UL https://hdl.handle.net/20.500.14352/131076
LA eng
NO Lafoz, E., Campreciós, G., García-Calderó, H., Anton, A., Vilaseca, M., Ruart, M., Guasch, E., Garrabou, G., Delgado, T. C., Martínez-Chantar, M. L., García-Martínez, R., Gracia-Sancho, J., Hernández-Gea, V., & García-Pagán, J. C. (2021). Impact of lifestyle interventions targeting physical exercise and caloric intake on cirrhosis regression in rats. American journal of physiology. Gastrointestinal and liver physiology, 321(6), G603–G616. https://doi.org/10.1152/ajpgi.00191.2021
DS Docta Complutense
RD 22 mar 2026