2,4-dinitrophenol downregulates genes for diabetes and fatty liver in obese mice
Author and article information
Abstract
Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the visceral low-grade inflammatory obesity. While the noninsulin dependent diabetes mellitus (NIDDM)- and nonalcoholic fatty liver disease (NAFLD)-related genes are globally upregulated in HFD+low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD+high-dose LPS mice. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.
Cite this as
2015. 2,4-dinitrophenol downregulates genes for diabetes and fatty liver in obese mice. PeerJ PrePrints 3:e1229v1 https://doi.org/10.7287/peerj.preprints.1229v1Author comment
This is a revised submission to PeerJ for review.
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Supplemental Information
Cytokine array
Table S1 Raw data of a cytokine/chemokine array
RT-PCR array of cytokines in obese mice
Table S2 Raw data of RT-PCR arrary of cytokine/chemokine transcripts in HFD+1.2mg/kg LPS mice
RT-PCR array of obese mice
Table S3 Raw data of RT-PCR arrary of NAFLD-related transcripts in HFD+0.25mg/kg LPS mice
RT-PCR array of DNP-treated obese mice
Table S4 Raw data of RT-PCR arrary of NAFLD-related transcripts in HFD+0.25mg/kg LPS mice treated by DNP
Additional Information
Competing Interests
The authors declare there are no competing interests.
Author Contributions
Qian Gao performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, prepared figures and/or tables, reviewed drafts of the paper.
Jiang He performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Tao Liao performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, reviewed drafts of the paper.
Qing-Ping Zeng conceived and designed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
All animal procedures were in accordance with the animal care committee at the Guangzhou University of Chinese Medicine, Guangzhou, China. The protocol was approved by the Animal Care Welfare Committee of Guangzhou University of Chinese Medicine (PermitNumber: SPF-2011007).
Microarray Data Deposition
The following information was supplied regarding the deposition of microarray data:
They will be provided prior to publication.
Funding
Financial support was provided by the National Science Foundation of China (NSFC) with the grant number 81273620. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.