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. 2023 Mar 23:14:1130350.
doi: 10.3389/fendo.2023.1130350. eCollection 2023.

The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model

Dongming Wu  1 , Zhenyuan Zhang  2   3   4   5 , Wenxiu Sun  6 , Yong Yan  7 , Mengzhe Jing  2   3   4   5 , Shizhan Ma  2   3   4   5
Affiliations

The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model

Dongming Wu et al. Front Endocrinol (Lausanne). .

Abstract

Background: Previous research has shown a tight relationship between the G0/G1 switch gene 2 (G0S2) and metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and obesity and diabetes, and insulin resistance has been shown as the major risk factor for both NAFLD and T2DM. However, the mechanisms underlying the relationship between G0S2 and insulin resistance remain incompletely understood. Our study aimed to confirm the effect of G0S2 on insulin resistance, and determine whether the insulin resistance in mice fed a high-fat diet (HFD) results from G0S2 elevation.

Methods: In this study, we extracted livers from mice that consumed HFD and received tail vein injections of AD-G0S2/Ad-LacZ, and performed a proteomics analysis.

Results: Proteomic analysis revealed that there was a total of 125 differentially expressed proteins (DEPs) (56 increased and 69 decreased proteins) among the identified 3583 proteins. Functional enrichment analysis revealed that four insulin signaling pathway-associated proteins were significantly upregulated and five insulin signaling pathway -associated proteins were significantly downregulated.

Conclusion: These findings show that the DEPs, which were associated with insulin resistance, are generally consistent with enhanced insulin resistance in G0S2 overexpression mice. Collectively, this study demonstrates that G0S2 may be a potential target gene for the treatment of obesity, NAFLD, and diabetes.

Keywords: G0S2; high-fat diet; insulin sensitivity; label-free proteomics; metabolic diseases.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
G0S2 increased HFD-induced obesity and insulin resistance. (A) Fasting body weight of mice in G0S2 normal expression group (HFD) and G0S2 overexpression group (HFD+G0S2 overexpress). (B, C) Representative GTT (B) and ITT (C) results of mice in the two given groups. (D) Western blot and RT-PCR were used to analyze the levels of G0S2 gene in mice that did and did not receive tail vein injections of Ad-G0S2 after HFD feeding for 16 weeks in all. *P<0.05; **P<0.01 compared with HFD-vehicle mice.
Figure 2
Figure 2
Differentially expressed proteins in the liver tissue of HFD-G0S2 overexpression mice.
Figure 3
Figure 3
Gene Ontology (GO) enrichment analysis of molecular function for DEPs. (A) Pie chart of DEP-enriched GO terms for molecular function (MF). (B) Max level for MF.
Figure 4
Figure 4
Gene Ontology (GO) enrichment analysis of biological processes for DEPs. (A) Pie chart of DEP-enriched GO terms for biological processes (bp). (B) Enriched GO terms for bp.
Figure 5
Figure 5
Gene Ontology (GO) enrichment analysis of biological processes for DEPs involved in insulin signaling pathways. (A) Heatmap of nine DEPs in response to insulin. (B) Protein–protein interaction (PPI) network of DEPs associated with the response to insulin. The red signal represents upregulation and green signal represents downregulation. The red pentagram represents the most pronounced upregulation and green pentagram represents the most pronounced downregulation,.
Figure 6
Figure 6
Insulin resistance was evaluated using western blotting and RT-PCR analysis. Upregulation of phosphatase Foxo1, Socs3, and Ptpn1, and downregulation of Gstp1 and PPAR-γ in the livers of HFD-G0S2 overexpression mice were determined by western blotting and RT-PCR in liver tissue. The experiment was repeated three times, using three independent batches of mice and three independent mice in each group. *P<0.05.
Figure 7
Figure 7
The genes involved in insulin resistance were evaluated using RT-PCR analysis in primary mouse hepatocytes. Downregulation of the phosphatases Foxo1, Socs3, and Ptpn1, as well as upregulation of Gstp1 and PPAR-γ, were determined in primary mouse hepatocytes isolated from G0S2-overexpressing mice (HFD+G0S2 overexpression) by RT-PCR. *P<0.05, **P<0.01. ns, P>0.05.
Figure 8
Figure 8
The proteins involved in insulin resistance were evaluated using western blotting analysis in primary mouse hepatocytes. Downregulation of the phosphatases Foxo1, Socs3, and Ptpn1, as well as upregulation of Gstp1 and PPAR-γ, were determined in primary mouse hepatocytes isolated from G0S2-overexpressing mice (HFD+G0S2 overexpression) by western blotting. *P<0.05, **P<0.01, ns P>0.05.
Figure 9
Figure 9
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs. (A) Pie chart of DEP-enriched KEGG pathways. (B) KEGG pathway enrichment distribution of DEPs.
Figure 10
Figure 10
Protein–protein interaction (PPI) network analysis of differentially insulin resistance-associated proteins.
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