How high-fat diet causes obesity

Mechanisms behind impaired insulin receptor (INSR) signaling in obesity induced by a high-fat diet remain elusive.
The researchers show that high-fat diet induces phosphorylation of nuclear translocation of SREBP-1c (Sterol Regulatory Element-Binding Protein 1c) and induces expression of the E3 ubiquitin ligase TRIM32. TRIM32 impairs cellular insulin action by degrading cell surface insulin receptors in the liver.
They also show that hepatic downregulation of TRIM32 increases insulin receptor expression and increases hepatic and systemic insulin sensitivity in high-fat diet-fed mice.
https://www.embopress.org/doi/full/10.1038/s44319-024-00348-7
https://sciencemission.com/TRIM32-regulates-insulin-sensitivity