ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This cross-sectional study explored the relationship between obesity and skeletal muscle protein synthesis, focusing on the expression of IGF-I and its mRNA splice variants. It provides insights into how obesity might impair protein synthesis and IGF-I levels, potentially contributing to the reduced muscle quality observed in obese patients.

This study explored IGF-I expression in the muscles of obese patients as a potential factor contributing to their impaired muscle protein synthesis (1). It enrolled 9 adult volunteers with obesity and nine controls, matched for age and height. Muscle biopsy was performed to analyse mitochondrial function. Blood samples were collected for IGF-I, glucose, insulin and d9-leucine enrichment, that represents a marker of synthesis rates of muscle proteins (2,3). Obese patients showed lower mixed-muscle protein fractional synthesis rate compared to the controls, in addition to lower levels of mitochondrial protein synthesis. Obese patients had also lower expression of IGF-I and its receptor in their skeletal muscles compared to normal weight subjects. The expression of specific IGF-I mRNA splice variants, named IGF-I Eb and Ec, was lower in the muscle tissue of obese individuals. These splice variants are critical for muscle growth and repair and are closely related to mitochondrial protein synthesis in the skeletal muscle of healthy individuals but not in those with obesity (4).

These findings provide new insights into the molecular mechanisms underlying muscle dysfunction in obese subjects and highlight the need for further research to develop targeted interventions to mitigate these effects (5). The reduced expression of IGF-I suggests that therapeutic strategies aimed at increasing IGF-I signaling may improve muscle protein synthesis and overall muscle health in obese individuals.

References: 1. Vassilakos G, Barton ER. Insulin-Like Growth Factor I Regulation and Its Actions in Skeletal Muscle. Compr Physiol. 2018 Dec 13;9(1):413-438. doi: 10.1002/cphy.c180010. PMID: 30549022.2. Guillet C, Delcourt I, Rance M, Giraudet C, Walrand S, Bedu M, Duche P, Boirie Y. Changes in basal and insulin and amino acid response of whole body and skeletal muscle proteins in obese men. ` J Clin Endocrinol Metab. 2009 Aug;94(8):3044-50. doi: 10.1210/jc.2008-2216. Epub 2009 May 26. PMID: 19470633.3. Tran L, Masters H, Roust LR, Katsanos CS. A new method to measure muscle protein synthesis in humans by endogenously introduced d9-leucine and using blood for precursor enrichment determination. Physiol Rep. 2015 Aug;3(8):e12479. doi: 10.14814/phy2.12479. PMID: 26243214; PMCID: PMC4562565.4. Brisson BK, Barton ER. Insulin-like growth factor-I E-peptide activity is dependent on the IGF-I receptor. PLoS One. 2012;7(9):e45588. doi: 10.1371/journal.pone.0045588. Epub 2012 Sep 21. PMID: 23029120; PMCID: PMC3448668.5. O’Neill BT, Lauritzen HP, Hirshman MF, Smyth G, Goodyear LJ, Kahn CR. Differential Role of Insulin/IGF-1 Receptor Signaling in Muscle Growth and Glucose Homeostasis. Cell Rep. 2015 May 26;11(8):1220-35. doi: 10.1016/j.celrep.2015.04.037. Epub 2015 May 14. PMID: 25981038; PMCID: PMC4449334.