Oxysterol-binding protein-like 3 is a novel target gene of peroxisome proliferator-activated receptor γ in fatty liver disease

Aibara, Daisuke; Sakaguchi, Ai; Matsusue, Kimihiko

doi:10.1016/j.mce.2023.111887

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…Not much is known regarding the role of SOX30 in adiposity traits although Sox30 knockout mouse displays altered fasting glucose levels (according to Mouse Genome Informatics (MGI) database, https://www.informatics.jax.org/). OSBPL3 is primarily known for tumor growth regulation, but has recently been linked to fatty liver disease via PPARG -dependent mechanisms (45, 46). Interestingly, Osbpl3 knockout mouse were found to display decreased body fat and increased lean body mass (according to MGI database search).…”

Section: Discussionmentioning

confidence: 99%

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity

Wang,

Sesachalam,

Chua

et al. 2023

Preprint

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ObjectiveVisceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene-regulatory networks in human visceral obesity are lacking.MethodsWe analyzed gene-regulatory networks in human visceral adipose tissue (VAT) from 48 obese and 11 non-obese Chinese subjects using gene co-expression and network construction with RNA-sequencing data. We also conducted RNA interference-based tests on selected genes for adipocyte differentiation effects.ResultsA scale-free gene co-expression network was constructed from 360 differentially expressed genes between obese and non-obese VAT (absolute log fold-change >1, FDR<0.05) with edge probability >0.8. Gene regulatory network analysis identified candidate transcription factors associated with differentially expressed genes. Fifteen subnetworks (communities) displayed altered connectivity patterns between obese and non-obese networks. Genes in pro-inflammatory pathways showed increased network connectivities in obese VAT whereas the oxidative phosphorylation pathway displayed reduced connections (enrichment FDR<0.05). Functional screening via RNA interference identifiedSOX30andOSBPL3as potential network-derived gene candidates influencing adipocyte differentiation.ConclusionsThis interactome-based approach highlights the network architecture, identifies novel candidate genes, and leads to new hypotheses regarding network-assisted gene regulation in obese vs. non-obese VAT.What is already known about this subject?Visceral adipose tissue (VAT) is associated with increased levels of proinflammatory activity, insulin resistance, diabetes risk and mortality rate.Gene expression studies have identified candidate genes associated with proinflammatory function in VAT.What are the new findings in your manuscript?Using integrative network-science, we identified co-expression and gene regulatory networks that are differentially regulated in VAT samples from subjects with and without obesityWe used functional testing (adipocyte differentiation) to validate a subset of novel candidate genes with minimal prior reported associations to obesityHow might your results change the direction of research or the focus of clinical practiceNetwork biology-based investigation provides a new avenue to our understanding of gene function in visceral adiposityFunctional validation screen allows for the identification of novel gene candidates that may be targeted for the treatment of adipose tissue dysfunction in obesity

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Section: Discussionmentioning

confidence: 99%

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity

Wang,

Sesachalam,

Chua

et al. 2023

Preprint

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“…hepatic fat accumulation [30]. Interleukin-6 (IL-6), encoded by the IL6 gene, influences peripheral lipid metabolism [31].…”

Section: E P T E Dmentioning

confidence: 99%

Genome-wide association studies of the fatty acid composition of Korean native chicken breast meat

Munyaneza,

Kim,

Cho

et al. 2024

J Anim Sci Technol

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“…Western blotting was performed as previously described (Aibara et al, 2023; Aibara, Takahashi, et al, 2022). The following antibodies were used: anti‐ADIG goat IgG (EB12488; Everest Biotech) and anti‐histone H3 rabbit IgG (#4620; Cell Signaling Technology).…”

Section: Experimental Proceduersmentioning

confidence: 99%

Transcriptional regulation of adipogenin expression in liver steatosis by hepatic peroxisome proliferator‐activated receptor gamma

2023

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The nuclear receptors peroxisome proliferator‐activated receptor gamma (PPARγ) and adipogenin (ADIG) play vital roles in lipid metabolism. However, the interaction between PPARγ and ADIG during liver steatosis remains unclear. In this study, we aimed to investigate the role of PPARγ in the transcriptional regulation of hepatic ADIG expression. Adig was found to be highly expressed in various fatty liver mouse models. Although hepatic Adig was expressed at high levels in the fatty liver of type 2 diabetic ob/ob mice and was upregulated by PPARγ agonist treatment, it was expressed at significantly low levels in liver‐specific Pparg‐knockout mice. Moreover, hepatic Adig expression was observed in other mouse models of liver steatosis, such as the leptin receptor mutant db/db and alcohol‐fed mice. Adig was also highly expressed in the white and brown adipose tissues, skeletal muscles, and heart of ob/ob mice. Reporter and electromobility shift assays showed that PPARγ positively regulates Adig transcriptional activity by directly binding to a functional PPARγ‐responsive element in the promoter region. Our results indicate that Adig is a novel target gene of hepatic PPARγ in liver steatosis.

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Oxysterol-binding protein-like 3 is a novel target gene of peroxisome proliferator-activated receptor γ in fatty liver disease

Cited by 6 publications

References 35 publications

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity

Genome-wide association studies of the fatty acid composition of Korean native chicken breast meat

Transcriptional regulation of adipogenin expression in liver steatosis by hepatic peroxisome proliferator‐activated receptor gamma

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