PPARδ Activation Rescues Pancreatic β-Cell Line INS-1E from Palmitate-Induced Endoplasmic Reticulum Stress through Enhanced Fatty Acid Oxidation

Abstract EN

One of the key factors responsible for the development of type 2 diabetes is the loss of functional pancreatic β cells.

This occurs due to a chronic exposure to a high fatty acid environment.

ER stress is caused by an accumulation of irreversible misfold or unfold protein: these trigger the death of functional pancreatic β cells.

PPARδ is an orphan nuclear receptor.

It plays a pivotal role in regulating the metabolism of dietary lipids and fats.

However, the correlation between PPARδ of fatty acids and ER stress of pancreatic β cells is not quite clear till date.

Here, we show that PPARδ attenuates palmitate-induced ER stress of pancreatic β cells.

On the other hand, PPARδ agonist inhibits both abnormal changes in ER structure and activation of signaling cascade, which is downstream ER stress.

Further, we illustrate that PPARδ attenuates palmitate-induced ER stress by promoting fatty acid oxidation through treatment with etomoxir, an inhibitor of fatty acid oxidation.

It dramatically abolishes PPARδ-mediated inhibition of ER stress.

Finally, we show that PPARδ could protect pancreatic β cells from palmitate-induced cell death and dysfunction of insulin secretion.

Our work elucidates the protective effect of PPARδ on the fatty-acid-induced toxicity of pancreatic β cells.