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Effects of deproteinized extract of calf blood on the energy metabolism of acute hypoxia model mice and its targets

ABSTRACT: Deproteinized extract of calf blood (DECB) can improve the transport and utilization of blood oxygen and glucose in hypoxic tissue cells, and accelerate the oxidative phosphorylation process of mitochondria, to improve the energy metabolism of cells. Due to its complex composition, the mechanism of DECB on energy metabolism is not entirely clear yet. Effects of DECB on the energy metabolism of acute hypoxia model mice were observed by detecting glucose, lactic acid, and protein and ATP contents in the brain, heart and liver of the mice. Differentially expressed genes related to the effect of DECB on the energy metabolism of acute hypoxia model mice were screened with the mRNA chip and the correlation analysis was performed. Hmgcs2, Cpt1a, Angptl4, Cyp8b1 and Ehhadh genes were involved in the energy metabolism in mice, and mainly closely related to some biological processes, including ABC transporters, adipocytokine signaling pathway and PPAR signaling pathway. DECB can improve the body energy metabolism in mice, of which Angptl4, Cyp8b1 and Ehhadh are important factors in regulating pathways of glucose metabolism, Hmgcs2 gene can directly provide the energy in the lack of energy in the body, and Cpt1a may regulate the inflammatory reaction and promote the energy metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE142545 | GEO | 2022/12/22

REPOSITORIES: GEO

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Project description:Studies in mice have shown that PPARÎ± is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARÎ± in human liver. Here we set out to compare the function of PPARÎ± in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARÎ± agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARÎ± expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARÎ± in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARÎ± targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPARÎ± in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARÎ± targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPARÎ± activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARÎ± as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARÎ± regulates a mostly divergent set of genes in mouse and human hepatocytes. GSE17250: Comparative analysis of gene regulation by the transcription factor PPARÎ±_mouse; GSE17251: Comparative analysis of gene regulation by the transcription factor PPARÎ±_human Experiment Overall Design: Refer to individual Series

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Effects of deproteinized extract of calf blood on the energy metabolism of acute hypoxia model mice and its targets

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