Irisin

2022-08-12: reference:

Irisin (Fibronectin type III domain-containing protein 5/FNDC5) #

• FNDC5 is cleaved at the C terminus to give rise to a 112-aa-long secreted hormone known as irisin. Small amoutns are synthesized in adipose tissue and the liver, but is mostly a myokine.
• It’s weird. It’s increased in both hyper and hypothyroidism, and in both diabetes and I believe insulin sensitivity? (considering it promotes)
• Irisin enhances longevity by boosting SIRT1, AMPK, autophagy and telomerase
• Inhibits Caspase 3
• The Role of PGC-1α/UCP2 Signaling in the Beneficial Effects of Physical Exercise on the Brain
  • Increases BDNF, which provides negative feedback loop to FNDC5.
    • Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway
  • Influencing the temperature of neuronal environments alters neurotransmission and enhances plasticity.
• [The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic β-Cell Survival and Insulin Secretion]
  • Stimulates insulin synthesis and glucose-stimulated insulin secretion in a PKA-dependent manner. Prevented SFA-induced apoptosis.
  • Increased levels of irisin observed in mice fed HFD.
• Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy
  • Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis.
  • Circulating irisin levels have been positively correlated with biceps circumference and IGF-1 levels in humans. In Myostatin-null mice, elevated irisin levels are seen.
  • Hypertrophy of skeletal muscle can be attributed to increased protein synthesis via the AKT-mTOR and AKT blocking GSK3, and also the ERK1/2 pathway… irisin treatment results in increased p-Erk expression.
  • Promotes browning of white adipose tissue via inducing expression of: UCP1, Cidea, Cpt1b, Dio2 in white Adipocytes - all of this is partly mediated by PPAR-α.
    • Hold up PGC-1 = PPAR-γ coactivator, nor PPAR-α. Am confused.
    • A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
      • PGC-1α expression in muscle stimulates an increase in expression of FNDC5. (Exercise increases PGC-1α)
  • Irisin increases myogenic differentiation and myoblast fusion via activation of IL-6 signaling.
    • I think it’s via STAT3
  • Significant reduction in Raptor Ser792 phosphorylation, indicative of mTOR activation.
• Destroys prostate Cancer independent of androgenic mechanisms