Activated Kupffer cells inhibit insulin sensitivity in obese mice

Simple item page
dc.contributor.authorTencerova, Michaela
dc.contributor.authorAouadi, Myriam
dc.contributor.authorYawe, Joseph C.
dc.contributor.authorCohen, Jessica L.
dc.contributor.authorGallagher-Dorval, Karen
dc.contributor.authorGupta, Olga T.
dc.contributor.authorCzech, Michael P.
dc.date.accessioned2023-04-13T19:31:57Z
dc.date.available2023-04-13T19:31:57Z
dc.date.issued2015
dc.description.abstractObesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.—Tencerova, M., Aouadi, M., Vangala, P., Nicoloro, S. M., Yawe, J. C., Cohen, J. L., Shen, Y., Garcia-Menendez, L., Pedersen, D. J., Gallagher-Dorval, K., Perugini, R. A., Gupta, O. T., Czech, M. P. Activated Kupffer cells inhibit insulin sensitivity in obese mice.en_US
dc.identifier.citationTencerova, M., Aouadi, M., Vangala, P., Nicoloro, S. M., Yawe, J. C., Cohen, J. L., ... & Czech, M. P. (2015). Activated Kupffer cells inhibit insulin sensitivity in obese mice. The FASEB Journal, 29(7), 2959.https://doi.org/10.1096%2Ffj.15-270496en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8465
dc.language.isoenen_US
dc.publisherThe FASEB Journalen_US
dc.subjecthepatic steatosisen_US
dc.subjectsmall interfering RNAen_US
dc.subjectinsulin resistanceen_US
dc.subjectliver macrophagesen_US
dc.titleActivated Kupffer cells inhibit insulin sensitivity in obese miceen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Activated Kupffer cells inhibit insulin sensitivity in obese mice.pdf
Size:
1.69 MB
Format:
Adobe Portable Document Format
Description:
Activated Kupffer cells inhibit insulin sensitivity in obese mice
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Medical and Health Sciences