title: Transcriptome analysis on the inflammatory cell infiltration of nonalcoholic steatohepatitis in bama minipigs induced by a long-term high-fat, high-sucrose diet.
abstract: Long-term adherence to a high-fat, high-calorie diet influences human health and causes obesity, metabolic syndrome and nonalcoholic steatohepatitis (NASH). Inflammation plays a key role in the development of NASH; however, the mechanism of inflammation induced by over-nutrition remains largely unknown. In this study, we fed Bama minipigs a high-fat, high-sucrose diet (HFHSD) for 23 months. The pigs exhibited characteristics of metabolic syndrome and developed steatohepatitis with greatly increased numbers of inflammatory cells, such as lymphocytes (2.27-fold, P<0.05), Kupffer cells (2.59-fold, P<0.05), eosinophils (1.42-fold, P<0.05) and neutrophils (2.77-fold, P<0.05). High-throughput RNA sequencing (RNA-seq) was performed to explore the systemic transcriptome of the pig liver during inflammation. Approximately 18.2 gigabases of raw sequence data were generated, and over 303 million high-quality reads were assembled into 21,126 unigenes. RNA-seq data analysis showed that 822 genes were differentially expressed in liver (P<0.05) between the HFHSD and control groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the process of inflammation involved the inflammatory signal transduction-related toll-like receptor, MAPK, and PPAR signaling pathways; the cytokine-related chemokine signaling, cytokine-cytokine receptor interaction, and IL2, IL4, IL6, and IL12 signaling pathways; the leukocyte receptor signaling-related T cell, B cell, and natural killer cell signaling pathways; inflammatory cell migration and invasion- related pathways; and other pathways. Moreover, we identified several differentially expressed inflammation-related genes between the two groups, including FOS, JUN, TLR7, MYC, PIK3CD, VAV3, IL2RB and IL4R, that could be potential targets for further investigation. Our study suggested that long-term HFHSD induced obesity and liver inflammation, providing basic insight into the molecular mechanism of this condition and laying the groundwork for further studies on obesity and steatohepatitis.
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Jihan
authors.initials: J
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China; College of Animal Science, Yangtz University, Jinzhou, Hubei, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Xin
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Kong
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, P. R. China.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D030561:Databases, Nucleic Acid; D004040:Dietary Carbohydrates / Q000009:adverse effects* / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013395:Sucrose / Q000009:adverse effects* / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D059467:Transcriptome
chemical_list: D016207:Cytokines; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D013395:Sucrose