Investigating the role of fibroblast growth factor 21 (FGF21) as an autophagic inducer during injury and regeneration following hepatic resection associated with ischemia-reperfusion in diabetic and healthy mice.
Introduction: In clinical condition, partial hepatectomy (PH) under ischemia-reperfusion (I/R) is commonly accomplished to control bleeding during hepatic resection. It is well known that I/R significantly reduces liver regeneration after hepatectomy. Diabetes mellitus (DM) is particularly associated with poor prognosis of I/R injury. Fibroblast growth factor 21 (FGF21) has beneficial metabolic effects in animal models of DM. FGF21 activate silent mating type information regulator 2 homolog 1 (SIRT1) pathway. SIRT1 plays important roles in the regulation of autophagy. Autophagy during the early phase of liver regeneration may be essential for preserving cellular quality. Aims: 1) to identify the generation of FGF21 in diabetic mice livers undergoing PH under I/R; 2) to evaluate if FGF21 is able to stimulate autophagy and the consequents effects of this homeostatic mechanism on liver injury and regeneration; 3) to investigate whether modulating of FGF21 and proteins associated with autophagy could protect livers against damage and regenerative failure following surgery; 4) to evaluate if adipose tissue as well participate as a source of generation of FGF21 after the submission of the diabetic mice livers to surgical procedure. Methods: Wild (C57BL/6) and diabetics (alloxan, 60mg/kg, i.v.) mice will be undergoing to liver surgery and the effects of different pharmacological treatments on hepatic injury and regeneration, and the underlying mechanisms, will be investigated. As DM is one of the diseases that most victimize the world population, increasing knowledge about PH under I/R, including in diabetic subjects, is of fundamental relevance.
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