Irisin Prevents High-Fat Diet-Induced Metabolic Disorders Via Brown Adipose Tissue Activation

Background High-fat diet (HFD) induces negative effects on interscapular brown adipose tissue (iBAT) activity and systemic energy metabolism. Irisin, a small hormonal agent known to modulate metabolism has been used for intervening HFD induced obesity. However, its mechanism of actions on iBAT function remains to be fully elucidated. This study sought to investigate whether an intervention with irisin could restore the thermogenic function of iBAT in HFD-induced mice with obesity, thereby regulating systemic metabolism. Methods Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) were used to determine and follow the changes of thermogenic capacity of iBAT and systemic metabolism in mice with obesity and iBAT-deficient mice during intervention with irisin for varying periods of time. Pathological and molecular biology analyses were performed on tissue and blood samples. Results Prolonged HFD feeding in mice induced obesity and impaired the thermogenic capacity of iBAT. MRI showed that irisin intervention decreased lipid content in iBAT, coupled with increased uncoupling protein 1 (UCP 1) expression and glucose analogue uptake capacity. This restoration of iBAT activity was accompanied by an improvement in systemic metabolism. The beneficial effects of irisin appears to be dependent on the length of intervention time. When iBAT was removed, the positive effects of irisin were partially suppressed, suggesting that irisin regulates metabolism through the restoration of the thermogenic function of iBAT. Conclusions HFD results in reduced thermogenic capacity of iBAT, while irisin intervention can effectively restore iBAT function, leading to improvement in overall glucose and lipid metabolism.