The unfolded protein response induced by endoplasmic reticulum stress promotes lipid synthesis in the crop tissues of pigeons during the breeding period

内质网应激诱导的未折叠蛋白反应促进鸽子繁殖期嗉囊组织中的脂质合成。

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Abstract

The endoplasmic reticulum stress (ERS) plays an important role in lipid deposition in mammals, but little is known in bird. In the present study, forty-two pairs of adult pigeons were randomly divided into the following 7 groups: Day 4 (I4), Day 10 (I10), and Day 17 (I17) of incubation, Day 1 (R1), Day 7 (R7), Day 15 (R15), and Day 25 (R25) of chick rearing. Crop tissues were sampled, and Gene Ontology (GO) enrichment analysis revealed upregulated differentially expressed genes were enriched in ERS, IRE1/PERK/ATF6-mediated unfolded protein response (UPR), and lipid synthesis-related pathways (I4 vs. R1). Additionally, accumulation of lipid droplets was greater at R1. The transcript levels of HSPA5 in males and females were upregulated at R1. The proteins upregulated at I17 and R1 in male and female pigeons included XBP1s, PERK, p-eIF2α, and ATF6. The mRNA abundances of the lipogenic genes of ACLY, ACACA, FASN, ELOVL6, GK, and DGAT2 showed distinct sex-specific timing, with peaks occurring from I17 to R1 in males and peaks occurring from R1 to R7 in females. Eighteen pairs of adult pigeons at I14 were assigned to 3 groups, namely, the C, T1 and T2 groups; pigeons in these groups were fed 4-PBA for one week at dosages of 0, 50 mg, and 100 mg (per pigeon/day), respectively. Oil Red O staining revealed 4-PBA attenuated lipid accumulation in pigeons. Treatment with 4-PBA significantly downregulated transcripts of HSPA5, ATF3, and DNAJB11 in males and HSPA5, DNAJB11, and BHLHA15 in females. Moreover, 4-PBA significantly decreased the translational levels of XBP1s, PERK, p-eIF2α, and ATF6 in males and XBP1s and PERK in females. Moreover, the transcript levels of ACACA, FASN, ELOVL6, and DGAT2 in males and those of ACLY and DGAT2 in females were also inhibited by 4-PBA. In conclusion, ERS-mediated UPR contributes to and is functionally linked with the elevated lipid synthesis (upregulated genes like ACLY, FASN, DGAT2, etc) during pigeon milk production.

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