Transcription factor-driven co-expression networks reveal liver responses to dietary lipids in pigs

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  • Presentation type: Poster
  • Track: PhD (Doctorate)
  • Keywords: regulatory mechanisms; fatty acids; metabolism; diseases; animal model;
  • 1 Faculdade de Zootecnia e Engenharia de Alimentos - Universidade de São Paulo
  • 2 Wageningen University & Research
  • 3 Universidade de São Paulo (USP), Escola Superior de Agricultura Luiz de Queiroz (ESALQ) - Piracicaba/SP
  • 4 Escola Superior de Agricultura Luiz de Queiroz - Universidade de São Paulo
  • 5 Escola Superior de Agricultura "Luiz de Queiroz"

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Abstract

Fatty acids (FA) modulate gene expression mainly by altering membrane lipids or through enzyme signaling pathways. Additionally, FA can influence gene regulation by modulating the activity or nuclear levels of transcription factors (TF). The TF associated with diets containing different proportions of soybean oil remain unknown. Therefore, we aimed to identify the TF involved in modulating diets with different soybean oil addition levels (1.5%, SOY1.5 or 3%, SOY3.0) in pig’s liver. Immunocastrated male Large White pigs were divided into two groups: SOY1.5 (17 animals) and SOY3.0 (18 animals) during a 98-day experiment conducted under the ethical statement CEUA2018-28. Total liver RNA was extracted and mRNA was sequenced by Illumina Technology. Bioinformatics analyses included FastQC to evaluate RNA-Seq data quality. TrimGalore removed sequencing adapters and low complexity reads. Bowtie2 aligned the reads to the Sus scrofa 11.1 genome, and RSEM quantified gene expression in TPM. We used WGCNA/R to find sets of co-expressed genes and correlated then to FA deposition. Fatty acids deposited from the liver included polyunsaturated fatty acids, palmitoleic acid, oleic acid, α-linolenic acid, total saturated fatty acids, monounsaturated fatty acids, and the PUFA:SFA ratio. We used Enrichr to predict the TF within relevant gene modules. Predicted TF revealed diet-specific regulatory patterns. In SOY1.5, we identified FOXP3 associated with the Black module, and HNF1A with the Darkorange2 module. In contrast, SOY3.0 showed HDAC2 and STAT3 as predicted regulators in the Pink module, indicating distinct transcriptional responses to lipid levels. The identified TF include regulators of T cells, such as FOXP3, as well as factors involved in maintaining cellular homeostasis, such as HNF1A. HDAC2, on the other hand, plays a key role in liver disease pathogenesis, and STAT3 is also implicated in liver disease development. Dietary lipid levels were found to modulate hepatic gene co-expression networks and TF in pigs.

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