Irisin deficiency exacerbates diet-induced insulin resistance and cardiac dysfunction in type II diabetes in mice

Am J Physiol Cell Physiol. 2023 Sep 11. doi: 10.1152/ajpcell.00232.2023. Online ahead of print.ABSTRACTMyokine Irisin is involved in the regulation of a variety of physiological conditions, metabolism, and survival. We and others have demonstrated that recombinant irisin contributes critically to modulation of insulin resistance and the improvement of cardiac function. However, whether deletion of irisin will regulates cardiac function and insulin sensitivity in type II diabetes remains unclear. We utilized the CRISPR/Cas-9 genome-editing system to delete irisin globally in mice and high fat diet (HFD)-induced type II diabetes model. We found that irisin deficiency did not result in developmental abnormality during adult stage, which illustrates normal cardiac function and insulin sensitivity in the absence of stress. The ultrastructural analysis of the transmission electronic microscope (TEM) indicated that deletion of irisin did not change the morphology of mitochondria in myocardium. Gene expression profiling showed that several key signaling pathways related to integrin signaling, extracellular matrix and insulin-like growth factors signaling were coordinately downregulated by deletion of irisin. When mice were fed with a HFD for sixteen weeks, ablation of irisin in mice exposed to HFD resulted in much severer insulin resistance, metabolic derangements, profound cardiac dysfunction and hypertrophic response and remodeling as compared with wild type control. Taken together...
Source: American Journal of Physiology. Cell Physiology - Category: Cytology Authors: Source Type: research