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Updated: Dec 5, 2025

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Disordered metabolism in mice lacking irisin.

Yunyao Luo1,2,3,4, Xiaoyong Qiao1,2,3,4, Yaxian Ma1,2,3,4

  • 1Reproductive Endocrinology and Regulation Laboratory West China Second University Hospital, Sichuan University, #20 Section 3, Ren Min Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.

Scientific Reports
|October 16, 2020
PubMed
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Irisin deficiency impairs the browning response, leading to metabolic issues like insulin resistance and hyperlipidemia. It also reduces bone mass by increasing bone resorption, highlighting irisin

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Bone Biology

Background:

  • Irisin, a fibronectin type III domain-containing protein 5 (Fndc5) product, influences adipokine secretion and osteoblast/osteoclast differentiation.
  • Understanding irisin's role in glucose/lipid and bone metabolism is crucial for metabolic and skeletal health.

Purpose of the Study:

  • To investigate the effects of irisin deficiency on glucose/lipid metabolism and bone health.
  • To characterize the metabolic and skeletal phenotypes of irisin-lacking mice.

Main Methods:

  • Generation of irisin-lacking mice via Fndc5 gene knockout.
  • Assessment of adipose tissue characteristics, glucose/lipid profiles, insulin sensitivity, bone strength, bone mass, osteoclast activity, and inflammatory markers (IL-6, TNF-α).

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Main Results:

  • Irisin deficiency resulted in impaired "browning response," characterized by larger white adipocytes and fewer brown adipocytes.
  • Mice lacking irisin exhibited hyperlipidemia, insulin resistance, reduced HDL-cholesterol, increased LDL-cholesterol, and decreased insulin sensitivity.
  • Bone mass and strength were reduced in irisin-lacking mice, accompanied by increased osteoclast numbers, elevated RANKL expression, and higher levels of IL-6 and TNF-α, indicating enhanced bone resorption and inflammation.

Conclusions:

  • Irisin deficiency is linked to a compromised "browning response," metabolic dysregulation (glucose/lipid metabolism), and diminished bone mass due to increased bone resorption.
  • These findings underscore the critical role of irisin in maintaining metabolic and skeletal homeostasis.
  • Further research is warranted to elucidate the precise mechanisms underlying irisin's multifaceted effects.