Lower muscle protein synthesis in humans with obesity concurrent with lower expression of muscle IGF1 splice variants

Obesity (Silver Spring). 2023 Nov;31(11):2689-2698. doi: 10.1002/oby.23896. Epub 2023 Oct 16.

Abstract

Objective: This study tested the hypothesis that expression of insulin-like growth factor 1 (IGF-1) protein and mRNA splice variants is lower in skeletal muscle of humans with obesity who have a lower mixed-muscle protein fractional synthesis rate (MMP-FSR) when compared with individuals without obesity.

Methods: The study included nine participants with obesity (OB, mean [SD], BMI = 35 [3] kg/m2 , MMP-FSR = 0.06%/h [0.02%/h]) and nine participants without obesity (W-OB, BMI = 24 [3] kg/m2 , MMP-FSR = 0.08%/h [0.02%/h]; for both BMI and MMP-FSR p < 0.05). MMP-FSR and mitochondrial protein FSR were measured following an overnight fast.

Results: Along with lower MMP-FSR, OB participants displayed lower mitochondrial protein FSR (p = 0.03) compared with W-OB participants. Expression of IGF-1 (p = 0.04) and IGF-1 receptor (p < 0.01) proteins was lower in muscle of OB participants. In addition, OB participants had lower (p < 0.05) mRNA expression of IGF1 variants Eb and Ec. This study demonstrates that lower protein synthesis in muscle of humans with obesity occurs concurrently with lower expression of muscle IGF-1 and IGF-1 receptor proteins, as well as lower mRNA expression of the IGF1 splice variants.

Conclusions: These findings indicate that lower protein synthesis observed in muscle of humans with obesity may result from diminished muscle IGF1 gene expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Insulin-Like Growth Factor I* / genetics
  • Insulin-Like Growth Factor I* / metabolism
  • Mitochondrial Proteins / metabolism
  • Muscle Proteins*
  • Muscle, Skeletal / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism

Substances

  • Muscle Proteins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • RNA, Messenger
  • Mitochondrial Proteins
  • IGF1 protein, human