Scripties UMCG - Rijksuniversiteit Groningen
 
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Autophagy-inducer rapamycin alleviates malnutrition-associated liver steatosis :The role of autophagy in malnutrition induced liver damage

(2017) Weise, L.(Linnéa)

Background: Severe prolonged malnutrition in children is associated hepatic metabolic disturbances, related to poor clinical outcome. Research with a rat model of severe malnutrition showed liver steatosis and impaired hepatic synthetic function, associated with a reduction in mitochondrial function and autophagy flux. Autophagy is a cellular pathway for recycling cell organelles and proteins. Aim: Determine whether the induction of autophagy through rapamycin causes a reduction of hepatic steatosis and a change of hepatic mitochondrial structure in a mouse model of malnutrition. Methods: Mice were placed ad libitum on a low protein diet (1%), control diet (18%) or low protein diet with daily rapamycin-injections (1% + Rapa) for 14 days. General phenotypes were analyzed. Liver tissue was examined with histology and immunofluorescence staining. Results: A protein deficient diet caused a distinct phenotype with a decrease in body weight and length, which was not rescued by rapamycin treatment. Rapamycin alleviated malnutrition induced hepatic steatosis and improved tissue morphology with a significant decrease in lipid droplet count and size. Mitochondria in rapamycin treated liver seem to resemble a partial reversion to non-malnourished morphology. Discussion: Rapamycin might reduce lipid accumulation by removing damaged mitochondria through an increase in autophagy (mitophagy). Enhanced autophagy through rapamycin might induce lipolysis or autophagy-mediated removal of hepatic lipids (lipophagy). Conclusion: Autophagy seems to be involved in the development of malnutrition induced hepatic steatosis. Inducing autophagy might represent a treatment option for malnutrition induced hepatic dysfunction.






 
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