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Irisin: The Greek Goddess Hormone



Currently, one of the leading causes of death in the US is heart disease. This along with diabetes and obesity is shifting the focus towards various new diets and exercises to help lose weight and control these conditions. In the past decade, a lot of research work has been focused on understanding how the metabolism in our body can be increased, leading to the discovery of Irisin.

What is Irisin?

Irisin is a hormone, which was discovered in 2012, in the skeletal muscles of mice by Bruce Spiegelman and colleagues at the Dana-Farber Cancer Institute in Harvard University. The name Irisin was derived from the ancient messenger Greek goddess Iris to refer to its role as the muscles’ messenger to fat cells. It is a 122 amino-acid, exercise-induced, myokine (a cytokine synthesized and released by muscle contractions). Irisin is a product of the cleavage of Fibronectin type III domain-containing protein 5 (FNDC 5). The function and structure of irisin are considered to be similar in many mammals with a 100% similarity between mice and humans. 

Irisin is mainly secreted in the skeletal muscles, especially in the perimysium, endomysium, and nuclear parts. Apart from these, it is also expressed in adipose tissue, pancreas, sebaceous glands, and cardiac muscle.

Let’s talk about body fat.

In our body, we have two kinds of fat or adipose tissue namely-

  1. White Adipose Tissue (WAT) – These are the fat molecules we have been taught about and try to burn when exercising, which stores excess energy as white fat droplets. These droplets accumulate in the body and help us keep warm by providing insulation. However, in humans, too much WAT is harmful and leads to obesity along with a higher risk of developing diabetes, heart diseases, and other comorbidities.
  2. Brown Adipose Tissue (BAT) – It stores energy in a smaller space than WAT. The brown color of this tissue is due to the presence of iron-packed mitochondria. When brown fat is burnt, it creates heat without shivering as seen in white fat through a process called non-shivering thermogenesis. During this process, brown fat also burns calories and is hence seen as a potential treatment for obesity and related diseases.

Irisin and body fat 

Irisin belongs to the class of adipo-myokines which acts on both adipose as well as muscle tissues and is a thermogenic protein that promotes energy expenditure by WAT browning (i.e. WAT is converted to BAT). It has been discovered that irisin is present in the human body naturally, and that physical activity like cardio exercises influences the level of irisin circulating in the body.

According to a study published by Steward et al. exercise induces the transcriptional regulator PGC-1α (peroxisome proliferator-activated receptor-γ co-activator 1α) which is responsible for the synthesis of FNDC5. More FNDC5 leads to a greater titer of irisin in the body by cleavage. This leads to an increase in the number of brown fat cells as along with irsin, FNDC5 also influences the expression of UCP1 (Uncoupling Protein 1 or Thermogenin). UCP1 is a mitochondrial carrier protein, found in BAT, and plays a role in non-shivering thermogenesis.

Benefits of irisin

  1. It reduces blood sugar and diabetes as irisin reduces insulin resistance and increases glucose uptake via the AMP-activated kinase (AMPK) pathway. It also lowers hemoglobin A1C. Irisin is also known to help regulate maternal-fetal glucose homeostasis. In mouse models with Type 1 Diabetes Mellitus, it was found to repair the cells.
  2. Helps in weight loss by inducing PGC-1α and FNDC5 which convert white fat to brown fat. It also lowers total cholesterol levels in both men and women.
  3. It supports the skeletal system by promoting bone formation by promoting osteoblast differentiation and lowering osteoporosis. It is seen to be positively correlated with bone mineral density in adolescent females.
  4. It acts as an anti-aging agent. Cell death is influenced by the length of telomeres which are present on the tip of chromosomes. It has been seen that irisin increases this telomere length thereby promoting cell survival.
  5. It acts as an anti-cancer agent. It has been shown to increase apoptosis in malignant mammary cells, in breast cancers, thereby decreasing the viability and the ability to migrate from these cells. Also, it was found that it increases the sensitivity of malignant cells to chemotherapeutic treatments without causing harm to normal cells.
  6. In mouse models, Irisin can prevent atherosclerosis. It is seen in mice that are injected with irisin, that they gain protection against endothelial injury by inhibiting oxidative stress from LDL cholesterol. It is also seen to reduce blood pressure by increasing the levels of nitric oxide (via the AMPK-Protein Kinase 3/Akt-endothelial Nitric Oxide Synthase- Nitric Oxide pathway).
  7. In rodents, it was found to be responsible for neuroprotection through exercise for diseases such as cerebral ischemia by activating the Akt and Extracellular signal-regulated Kinases 1/2 (ERK 1/2) pathways of the brain. It can also protect against brain damage and increase neurogenesis via the Signal transducer and activator of the transcription 3 (STAT3) pathway.
  8. It was discovered that in otherwise healthy people, irisin levels can be a predictor of acute coronary syndrome. Also, it was found that decreased levels of irisin in patients with coronary artery disease treated by percutaneous interventions, survival rate are up to only a year.

Figure: Effect of irisin on different organs

Future implications

The discovery of irisin is still very recent in the scientific community. Not much is known about the hormone and its various functions and research is still being carried out at Harvard University, University of Bari Aldo Moro (Italy), Duke University, and Scripps Research Institute to name a few, to find out its potential. However, it has been established that irisin levels can be increased through exercise and are being looked at as a treatment for obesity and obesity-related complications. This breakthrough discovery is likely to pave the way to a healthier world and future.

Reference (A8-May-21)

Author Biography: I am currently pursuing my B.Tech in Medical Biotechnology from Pune. I have a keen interest in vaccine technology especially cancer vaccines and wish to pursue a career in the same and hopefully cause a difference and help people one day.

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