Disordered metabolism in mice lacking irisin

Yunyao Luo,Xiaoyong Qiao,Yaxian Ma,Hongxia Deng,Charles C Xu,Liangzhi Xu

doi:10.1038/s41598-020-74588-7

Abstract

Irisin is a product of fibronectin type III domain-containing protein (Fndc5) and is involved in the regulation of adipokine secretion and the differentiation of osteoblasts and osteoclasts. In this study, we aimed to determine whether irisin lacking affects glucose/lipid and bone metabolism. We knocked out the Fndc5 gene to generate irisin-lacking mice. Remarkable, irisin lacking was related to poor ‘browning response’, with a bigger size of the intraperitoneal white adipose cell and decreased a number of brown adipose cells in brown adipose of interscapular tissue. The irisin lacking mice had hyperlipidemia and insulin resistance, reduced HDL-cholesterol level, increased LDL-cholesterol level, and decreased insulin sensitivity. The lacking of irisin was associated with reduced bone strength and bone mass in mice. The increased number of osteoclasts and higher expression of RANKL indicated increased bone resorption in irisin lacking mice. The level of IL-6 and TNF-α also increased in irisin lacking mice. The results showed that irisin lacking was related to decreased ‘browning response’, glucose/lipid metabolic derangement, and reduced bone mass with increased bone resorption. Further studies are needed to confirm these initial observations and explore the mechanisms underlying the effects of irisin on glucose/lipid and bone metabolism.

Highlights

Irisin is a product of fibronectin type III domain-containing protein (Fndc5) and is involved in the regulation of adipokine secretion and the differentiation of osteoblasts and osteoclasts
Irisin is a recently described cytokine secreted by skeletal muscles and was discovered in 20121. It is derived from the 196 amino acid transmembrane protein fibronectin type III domain containing 5 (Fndc5), which is cleaved by specific p roteases[2,3]
KO mice had significantly reduced body weight, they had an increased intraperitoneal white adipose tissue ratio, and a decreased interscapular brown adipose tissue ratio compared to wild type mice (WT) mice (Fig. 2A; Table 1)

Summary

Introduction

Irisin is a product of fibronectin type III domain-containing protein (Fndc5) and is involved in the regulation of adipokine secretion and the differentiation of osteoblasts and osteoclasts. The results showed that irisin lacking was related to decreased ‘browning response’, glucose/lipid metabolic derangement, and reduced bone mass with increased bone resorption. Irisin is a recently described cytokine secreted by skeletal muscles and was discovered in 20121 It is derived from the 196 amino acid transmembrane protein fibronectin type III domain containing 5 (Fndc5), which is cleaved by specific p roteases[2,3]. Colaianni et al indicated that irisin injection prevented bone loss and induced recovery of bone mass in 2-month-old male mice[10]. These effects were consistent with in vitro studies in our lab, indicating that irisin enhances osteoblast differentiation but inhibits osteoclast precursor cell differentiation[11,12]. We knocked out the Fndc[5] gene to generate irisin lacking mice, to identify the multiple effects of irisin in metabolism

Objectives

Methods

Results

Conclusion