Role of ISR in SFA-induced GDF15 expression. (A,B) GDF15 expression measured by RT-qPCR in PMA-differentiated THP-1 cells treated with 200 µM C18:0 for 16 h after PERK silencing by siRNA (A) (n = 5) or in presence of 2 µM GSK2606414 (PERKi1) or GSK2656157 (PERKi2) (B) (n = 5). (C–E) GDF15 expression measured by RT-qPCR (C,E) or GDF-15 secretion in supernatant (SN) measured by luminex assay (D) in MDMs treated with 100 µM C18:0 or 5 µg/mL tunicamycin for 16 h in presence of 2 µM GSK2606414 (PERKi1) or GSK2656157 (PERKi2) (n = 4). (F,G) GDF15 expression measured by RT-qPCR after treatment with 200 µM C18:0 or 5 µg/mL tunicamycin for 16 hrs in PMA-differentiated THP-1 cells in presence of 1 µM trans-ISRIB or 50 µM salubrinal (n = 5). * p < 0.05, ** p < 0.01, *** p < 0.001 by two-way ANOVA with Sidak’s multiple comparisons test. Results are presented as mean ± SEM. FC, fold change.