Abstract

The epidemic of obesity has contributed to the rapid rise in comorbid conditions such as cardiovascular disease, type 2 diabetes, sleep apnea, and hypertension among others. Therefore, there is a critical need to develop therapeutic strategies to reduce the prevalence of the disease. Skeletal muscle cells secrete signaling cytokines/peptides (referred to as myokines) that act in autocrine, paracrine, and endocrine fashion. Myokines have been hypothesized to contribute to the immediate and chronic benefits of exercise and may thus serve as attractive therapeutic agents for the treatment of obesity. The recent discovery of the irisin, a proposed myokine, has gained much attention over the last two years as a potential therapeutic agent. Preliminary studies demonstrated that irisin has the potential to induce “browning” of white adipocytes in mice. If these findings in mice could be translated to humans, irisin could be a potential therapeutic agent for the treatment of obesity. Limitations with the available antibodies, however, have raised concerns regarding the detectability of irisin in circulation. Moreover, the gene encoding irisin, FNDC5, is expressed robustly not only in muscle but also in various white adipose tissues (WAT) in humans, raising the possibility for increased thermogenesis through autocrine mechanisms. Here we will discuss the browning of WAT, the discovery of irisin, and its potential role in improving metabolic health in humans.

Highlights

  • Obesity has rapidly become a worldwide epidemic

  • The authors concluded that these findings indicate that Fibronectin type III domaincontaining 5 (FNDC5) induces uncoupling protein 1 (UCP1)-positive cells to develop the beige/brite phenotype in mice [14]

  • Preliminary studies have indicated that recombinant FNDC5 and/or irisin can induce browning of murine white adipose tissues (WAT)

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Summary

Introduction

Obesity has rapidly become a worldwide epidemic. In parallel, the prevalence of obesity-related comorbid conditions has escalated, including insulin resistance, metabolic syndrome, type 2 diabetes, hypertension, chronic kidney disease, cardiovascular disease, heart failure, cancer, and dementia [1,2,3]. We will discuss the browning of WAT, the discovery of irisin, and its potential role in improving metabolic health in humans. The recent discovery of irisin by Bostrom et al [14], a putative exercise induced myokine, that is credited for improving metabolic health by its ability to brown white adipose tissue (WAT) in mice has received considerable attention over the last two years.

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