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. 2022 Jan 20;12:1048. doi: 10.1038/s41598-022-05140-y

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© The Author(s) 2022, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Analysis of down- and upregulated pathways in 6-mo Pcyt2^+/—liver. (A) Downregulated genes of 6-mo Pcyt2^+/− liver were analyzed with Enrichr (https://maayanlab.cloud/Enrichr/)^33–35 (n = 3). (A-a) The Mouse 2019 KEGG^38–40 pathway analysis and genes cluster analysis indicated that the most downregulated pathways included the growth factor (insulin, ErB, prolactin, cancer) pathways, and mTOR and AMPK pathways. (A-b) GO Biological Processes 2018 showed that the most downregulated processes were insulin signaling and glucose metabolism. (B) Upregulated genes of 6-mo old Pcyt2^+/− were analyzed with Enrich (n = 3). (B-a) WikiPathway Mouse 2019 established the most significantly upregulated gene clusters and pathways for insulin/EGFR signaling and pro inflammatory pathways mediated by IL2, IL9, IL5, IL6, and IL7 (B-b) Jansen Diseases analysis showed that the most upregulated were gene involved in hyperglycemia, hyperinsulinemia, and fatty liver disease. (C) Immunoblot analysis of Pi3k/Akt pathway in fasted and fed 6-mo Pcyt2^+/− (n = 4). Serum levels of liver enzymes ALT, AST, ALP in (D) 2-mo and (E) 6-mo Pcyt2^+/− (n = 12). Serum levels of albumin in (F) 2-mo and (E) 6-mo Pcyt2^+/− (n = 12). Histology of 8-mo liver with (H) H&E stain showing steatosis (blue circles), ballooned hepatocytes (black circles) with Mallory-Denk bodies (black arrows) and lobular inflammation (yellow arrows); (I) immunohistochemical stain with F4/80 showing macrophage infiltration; (J) Picrosirius red stain showing collagen deposition. Band intensities were measured using ImageJ. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Analysis of down- and upregulated pathways in 6-mo Pcyt2^+/—liver. (A) Downregulated genes of 6-mo Pcyt2^+/− liver were analyzed with Enrichr (https://maayanlab.cloud/Enrichr/)^33–35 (n = 3). (A-a) The Mouse 2019 KEGG^38–40 pathway analysis and genes cluster analysis indicated that the most downregulated pathways included the growth factor (insulin, ErB, prolactin, cancer) pathways, and mTOR and AMPK pathways. (A-b) GO Biological Processes 2018 showed that the most downregulated processes were insulin signaling and glucose metabolism. (B) Upregulated genes of 6-mo old Pcyt2^+/− were analyzed with Enrich (n = 3). (B-a) WikiPathway Mouse 2019 established the most significantly upregulated gene clusters and pathways for insulin/EGFR signaling and pro inflammatory pathways mediated by IL2, IL9, IL5, IL6, and IL7 (B-b) Jansen Diseases analysis showed that the most upregulated were gene involved in hyperglycemia, hyperinsulinemia, and fatty liver disease. (C) Immunoblot analysis of Pi3k/Akt pathway in fasted and fed 6-mo Pcyt2^+/− (n = 4). Serum levels of liver enzymes ALT, AST, ALP in (D) 2-mo and (E) 6-mo Pcyt2^+/− (n = 12). Serum levels of albumin in (F) 2-mo and (E) 6-mo Pcyt2^+/− (n = 12). Histology of 8-mo liver with (H) H&E stain showing steatosis (blue circles), ballooned hepatocytes (black circles) with Mallory-Denk bodies (black arrows) and lobular inflammation (yellow arrows); (I) immunohistochemical stain with F4/80 showing macrophage infiltration; (J) Picrosirius red stain showing collagen deposition. Band intensities were measured using ImageJ. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.