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Research
Dandong Wu
The second affiliated hospital of Chongqing medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8128-0611
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective
C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO.
Methods
Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-α and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-κB signaling cascade and microglial activation were also examined in vivo. In addition, NF-κB signaling and proinflammatory factors were investigated in BV2 cells after CTRP4 intervention.
Results
We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-α and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-κB signaling and microglial activation were also significantly suppressed in vivo. In addition, NF-κB signaling was inhibited in BV2 cells after CTRP4 intervention, which was consistent with the decreased production of TNF-α and IL-6.
Conclusions
Our data indicate that CTRP4 reverses leptin resistance by inhibiting NF-κB-dependent microglial activation and hypothalamic inflammation.
Keywords
CTRP4, leptin signaling, microglial activation, NF-κB signaling, diet-induced obesity
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View the published article at Journal of Neuroinflammation.
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Editorial decision: Major Revision
On 22 Feb, 2021
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Received 15 Feb, 2021
Review #1 received
Received 13 Feb, 2021
Reviewer #2 agreed
On 02 Feb, 2021
Reviewer #1 agreed
On 26 Jan, 2021
Reviewers invited
Invitations sent on 23 Jan, 2021
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On 14 Jan, 2021
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On 14 Jan, 2021
Editor invited
On 14 Jan, 2021
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Subject Areas
Neurobiology of Disease
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A new preprint design is coming!
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See the published version of this preprint at Journal of Neuroinflammation.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Dandong Wu
The second affiliated hospital of Chongqing medical university
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8128-0611
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Neuroinflammation.
Version 1
Posted 19 Jan, 2021
No community comments so far
Editorial decision: Major Revision
On 22 Feb, 2021
Review #2 received
Received 15 Feb, 2021
Review #1 received
Received 13 Feb, 2021
Reviewer #2 agreed
On 02 Feb, 2021
Reviewer #1 agreed
On 26 Jan, 2021
Reviewers invited
Invitations sent on 23 Jan, 2021
Editor assigned
On 14 Jan, 2021
Submission checks complete
On 14 Jan, 2021
Editor invited
On 14 Jan, 2021
First submitted
On 13 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Neuroinflammation.
Objective
C1qTNF-related protein 4 (CTRP4) acts in the hypothalamus to modulate food intake in diet-induced obese mice and has been shown to exert an anti-inflammatory effect on macrophages. Since high-fat diet-induced microglial activation and hypothalamic inflammation impair leptin signaling and increase food intake, we aimed to explore the potential connection between the anorexigenic effect of CTRP4 and the suppression of hypothalamic inflammation in mice with DIO.
Methods
Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and the hypothalamic leptin signaling pathway in diet-induced obese mice. Furthermore, central and plasma proinflammatory cytokines, including TNF-α and IL-6, were measured by Western blotting and ELISA. Changes in the hypothalamic NF-κB signaling cascade and microglial activation were also examined in vivo. In addition, NF-κB signaling and proinflammatory factors were investigated in BV2 cells after CTRP4 intervention.
Results
We found that food intake was decreased, while leptin signaling was significantly improved in mice with DIO after CTRP4 overexpression. Central and peripheral TNF-α and IL-6 levels were reduced by central Ad-CTRP4 administration. Hypothalamic NF-κB signaling and microglial activation were also significantly suppressed in vivo. In addition, NF-κB signaling was inhibited in BV2 cells after CTRP4 intervention, which was consistent with the decreased production of TNF-α and IL-6.
Conclusions
Our data indicate that CTRP4 reverses leptin resistance by inhibiting NF-κB-dependent microglial activation and hypothalamic inflammation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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