Propionate alleviates palmitic acid–induced endoplasmic reticulum stress by enhancing autophagy in calf hepatic cells

Negative energy balance–induced high blood concentrations of free fatty acids during the early postpartum period in dairy cows is a major cause liver injury. Cows severe negative balance often have suboptimal intakes feed, which contributes to shortfalls production ruminal propionate and circulating glucose. Although increasing by rumen through feed additives such as propylene glycol effective helping alleviate shortfall dietary supply, mechanisms whereby affects function beyond gluconeogenesis are unknown. Therefore, objective this study was investigate whether could protect calf hepatic cells from palmitic acid (PA)-induced lipotoxicity underlying mechanisms. Calf were isolated 5 healthy calves (1 d old, female, 30–40 kg, fasting) treated with various PA (0, 100, 200, or 400 ?M) 1, 2, 4 mM) after being administered without autophagic inhibitor. Propionate enhanced activity cells, indicated elevated expression autophagy markers LC3-II (microtubule-associated protein 1 light chain 3-II, encoded MAP1LC3) decreased SQSTM1 (sequestosome-1, also called p62). Conversely, suppressed cell viability, improved cells. In addition, phosphorylation proteins EIF2AK3 (kinase R/PKR like ER kinase) ERN1 (inositol-requiring enzyme 1?) cleaved ATF6 (activating transcription factor 6) PA-treated indicating suppression effect on endoplasmic reticulum (ER) stress. However, inhibition chloroquine bafilomycin A1 impede beneficial effects stress viability. These results demonstrated that alleviates elevates viability enhancing autophagy, implies may be promising target improving injury transition period.