Back to Search
Start Over
Insulin sensitization by hepatic FoxO deletion is insufficient to lower atherosclerosis in mice.
- Source :
-
BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 18. Date of Electronic Publication: 2023 Oct 18. - Publication Year :
- 2023
-
Abstract
- Background–: Type 2 diabetes is associated with an increased risk of atherosclerotic cardiovascular disease. It has been suggested that insulin resistance underlies this link, possibly by altering the functions of cells in the artery wall. We aimed to test whether improving systemic insulin sensitivity reduces atherosclerosis.<br />Methods–: We used mice that are established to have improved systemic insulin sensitivity: those lacking FoxO transcription factors in hepatocytes. Three hepatic FoxO isoforms (FoxO1, FoxO3, and FoxO4) function together to promote hepatic glucose output, and ablating them lowers glucose production, lowers circulating glucose and insulin, and improves systemic insulin sensitivity. We made these mice susceptible to atherosclerosis in two different ways, by injecting them with gain-of-function AAV8.mPcsk9 <superscript>D377Y</superscript> and by crossing with Ldlr <superscript>-/-</superscript> mice.<br />Results–: We verified that hepatic FoxO ablation improves systemic insulin sensitivity in these atherosclerotic settings. We observed that FoxO deficiency caused no reductions in atherosclerosis, and in some cases increased atherosclerosis. These phenotypes coincided with large increases in circulating triglycerides in FoxO-ablated mice.<br />Conclusions–: These findings suggest that systemic insulin sensitization is insufficient to reduce atherosclerosis.<br />Competing Interests: Conflict of interest statement. The authors have declared that no conflict of interest exists.
Details
- Language :
- English
- Database :
- MEDLINE
- Journal :
- BioRxiv : the preprint server for biology
- Accession number :
- 37905094
- Full Text :
- https://doi.org/10.1101/2023.10.14.562366