Expression of IGF-1 isoforms in skeletal muscle of humans with obesity and their associations with muscle protein synthesis

Abstract

PURPOSE: There are currently discrepant findings describing the effects of obesity on skeletal muscle protein metabolism, with some, but not all, studies reporting impaired protein synthesis in skeletal muscle. The underlying causes for the different findings remain unknown. Considering the importance of the insulin-like growth factor one (IGF-1) on skeletal muscle protein metabolism and stimulation of protein synthesis, we investigated the effects of obesity on the expression of the different isoforms of IGF-1 in skeletal muscle and their association with the rates of mixed-muscle and mitochondrial protein synthesis. METHODS: Seventeen adults with obesity (OB, males = 9, females = 7, BMI = 34.70 ± 3.13 kg/m2, age = 34.12±9.95 yrs) and 19 lean adults (LN, males = 8, females = 9, BMI = 23.35 ± 2.63 kg/m2, age = 32.47 ± 9.43 yrs) underwent infusion of d10-leu coupled with vastus lateralis muscle biopsies to measure fractional synthesis rate (FSR) of mixed-muscle (MMP) and mitochondrial proteins (MITOP) after an overnight (~ 10-h) fast. Muscle protein synthesis was evaluated using standard precursor-product approach, after determination of enrichment of plasma leucine and muscle proteins leucine with d10-leu by mass spectrometry. Predesigned TaqMan gene expression assays (Thermo Fisher Scientific Inc) were used to measure the mRNA expression of IGF-1 Ea, IGF-1 Eb, and IGF-1 Ec isoforms and ACTB (used as control). RESULTS: There were no significant differences between LN and OB in the FSR of MMP (LN = 0.07 ± 0.02, OB = 0.07 ± 0.02, p = 0.50) or MITOP (LN = 0.09 ± 0.03, OB = 0.08 ± 0.03, p = 0.17). Moreover, there were no significant group differences in the mRNA expression of either Ea (LN = 1.00 ± 0.45, OB = 1.09 ± 0.45, p = 0.62) or Ec (LN = 1.06 ± 0.68, OB = 0.93 ± 0.44, p = 0.47) isoforms of IGF-1. However, a significantly ( p = 0.04) lower mRNA expression of the Eb isoform was observed in the OB group (0.73 ± 0.28) compared to the LN group (1.11 ± 0.50). Although no significant correlations were observed in the mRNA expression between either Ea or Ec IGF-1 isoforms and MMP and MITOP FSR, a significant correlation was observed between the Eb isoform mRNA expression and MITOP ( r = 0.53, p = 0.02), whereas the correlation with MMP FSR only approached statistical significance ( r = 0.38, p = 0.07). CONCLUSION: These results suggest that mRNA expression of the IGF-1 Eb isoform is reduced in humans with obesity compared to lean. Also, reduced expression of the IGF-1 Eb isoform is associated with lower production of mitochondrial proteins in skeletal muscle. Therefore, lower muscle mRNA expression of the IGF-1 Eb isoform may be a culprit impairing synthesis of protein previously documented in skeletal muscle of humans with obesity. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.