Abstract:
Db/db mice with obesity (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ expression levels as diabetes markers. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and under expression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid chitinase (CHIA) in the liver of db/db mice. Compared to a control, CHIA expression in db/db mice is significantly lower only in the spleen, indicating different expression changes for these two enzymatically active chitinases. Trehalose treatment of db/db mice was followed by increased autophagy induction in the heart and liver (in addition to autophagy induction in the brain, as shown by us previously). Trehalose exerted the beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes. We propose some mechanisms for the observed positive influence of trehalose.
