Irisin reverses high-fat diet-induced metabolic dysfunction via activation of brown adipose tissue in mice.

Abstract

Background: High-fat diet (HFD) induces negative effects on the activity of interscapular brown adipose tissue (iBAT) 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 action on iBAT function remains to be fully elucidated. This study sought to investigate whether irisin intervention could restore the thermogenic function of iBAT in mice with HFD-induced obesity, thereby regulating systemic metabolism.

Methods: Magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) were used to monitor changes of thermogenic capacity of iBAT and systemic metabolism in mice with HFD-induced obesity and iBAT deficiency during 2-week or 4-week irisin intervention. 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 results showed that irisin intervention for 4-week reduced lipid content in iBAT, increased uncoupling protein 1 (UCP 1) expression and enhanced glucose analogue uptake capacity. These improvements of functions in iBAT activity were accompanied by an improvement in systemic metabolism. The positive effects of irisin appears to be dependent on the length of intervention time. When iBAT was removed, the beneficial 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.