Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Aug 2:10:524.
doi: 10.3389/fendo.2019.00524. eCollection 2019.

Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome

Lidia I Arhire  1   2 , Laura Mihalache  1   2 , Mihai Covasa  3   4
Affiliations
Review

Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome

Lidia I Arhire et al. Front Endocrinol (Lausanne). .

Abstract

White adipose tissue (WAT) is an endocrine organ highly integrated in homeostasis and capable of establishing ways of communicating and influencing multiple metabolic processes. Brown adipose tissue promotes energy expenditure by incorporating the uncoupling protein 1 (UCP1), also known as thermogenin, which decouples cellular respiration and heat production, in the mitochondrial membranes. Recent data suggest the presence of a thermogenic cell formation from white adipocytes (beige or brite cells) with a potential role in preventing obesity and metabolic syndrome. The formation of these cells is influenced by physical exertion that induces expression of PPARγ coactivator-1 (PGC1) and downstream membrane protein, fibronectin type III domain-containing protein 5 (FNDC5) in skeletal muscle. Irisin, a thermogenic adipomyokine produced by FNDC5 cleavage is involved in the browning of adipose tissue. While animal studies are congruent with regard to the relationship between physical exertion and irisin release, the results from human studies are less than clear. Therefore, this review focuses on recent advances in our understanding of muscle and adipose tissue thermogenesis. Further, it describes the molecular mechanisms by which irisin impacts exercise, glucose homeostasis and obesity. Finally, the review discusses current gaps and controversies related to irisin release, its mode of action and its future potential as a therapeutic tool in managing obesity and metabolic syndrome.

Keywords: adipokines; adipose tissue; exercise; skeletal muscle; thermogenesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Cold initiates shivering in skeletal muscle and a non-shivering phase in which brown and beige adipose tissue is activated to release heat via UCP-1. Shivering and exercise promote adipose tissue-mediated thermogenesis via secretion of irisin (30). Exercise increases transcriptional co-activator PGC1-α and induces expression of the FNDC5 gene. FNDC5 membrane protein is cleaved to release irisin into the bloodstream. Irisin is also released by adipocytes thus becoming an adipocytokine (18). Other sources such as the brain, pancreas, stomach, Kupffer cells, tongue, rectum, heart, testis, sinusoidal epithelial cells, and optic nerve also release irisin (31). Irisin promotes “browning” of mature white adipocytes in response to exercise (32, 33). Brown and beige adipose tissues increase energy expenditure through the uncoupling of oxidative metabolism from ATP production. This is a key function of UCP1 (34). PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1 alpha; FNDC5, Fibronectin type III domain-containing protein 5; WAT, white adipose tissue; BAT, brown adipose tissue; BEIGE, beige adipocyte, brite (“brown-in-white”), or inducible BAT; UCP1, uncoupling protein-1; SNS, sympathetic nervous system.
Figure 2
Figure 2
Circulating irisin originates mainly from skeletal muscle during activity of, and from, adipose tissue. Irisin acts locally, in an autocrine/paracrine manner, and when released into circulation, acts in a hormone-like fashion mediating peripheral activity (80). Irisin has multi-spectrum functions on various tissues or organs, inhibits adipogenic differentiation while promotes osteogenic differentiation (59). Irisin influences the function of skeletal muscle, pancreas (81), liver (82), brain (83), and bone (84, 85) enhances insulin sensitivity, metabolism, cognition, and osteogenesis. Irisin improves insulin resistance and type 2 diabetes by increasing sensitivity of the insulin receptor in skeletal muscle and heart, by improving hepatic glucose and lipid metabolism and by promoting pancreatic β cell functions, and browning of white adipose tissue (86). WAT, white adipose tissue; BDNF, brain-derived neurotrophic factor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Welle S. Endocrine, paracrine, and autocrine regulation. Human Protein Metabolism. New York, NY: Springer-Verlag Inc; (1999).
    1. Saely CH, Geiger K, Drexel H. Brown versus white adipose tissue: a mini-review. Gerontology. (2012) 58:15–23. 10.1159/000321319 - DOI - PubMed
    1. Vargas-Castillo A, Fuentes-Romero R, Rodriguez-Lopez LA, Torres N, Tovar AR. Understanding the biology of thermogenic fat: is browning a new approach to the treatment of obesity? Arch Med Res. (2017) 48:401–13. 10.1016/j.arcmed.2017.10.002 - DOI - PubMed
    1. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. (2007) 131:242–56. 10.1016/j.cell.2007.10.004 - DOI - PubMed
    1. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, et al. . General and abdominal adiposity and risk of death in Europe. N Engl J Med. (2008) 359:2105–20. 10.1056/NEJMoa0801891 - DOI - PubMed