Chemical Chaperone PBA Attenuates ER Stress and Upregulates SOCS3 Expression as a Regulator of Leptin Signaling

This study involved twenty-four lean and twenty-four leptin-deficient (ob/ob) mice divided into PBA- and vehicle-treated groups. Pancreatic islets were isolated, incubated with leptin for 48 h, and assayed for the expression of CHOP and XBP1s (UPR signaling indicators) and SOCS3 (regulator of leptin signaling) by RT-qPCR. The expression levels of XBP1s and CHOP were markedly increased in the ob/ob controls compared to other groups with and without leptin treatment. No significant differences in the XBP1s and CHOP expression levels were found between the PBA-treated ob/ob and lean mice. SOCS3 expression was significantly upregulated in the PBA-treated ob/ob mice compared to the ob/ob controls after leptin treatment; but no significant difference in the SOCS3 expression was found between the PBA-treated ob/ob and lean mice with and without leptin treatment. Our findings suggested that ER stress plays an important role in the pathology of obesity, while PBA reduces ER stress and may potentially ameliorate leptin signaling.
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research