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Is the metabolic response to sepsis in skeletal muscle different in infants and adults? An experimental study in rats
O Zamir1, P O Hasselgren, J A Frederick
1Department of Surgery, University of Cincinnati Medical Center, OH.
Insights
Sepsis impacts muscle protein metabolism similarly in infant and adult rats, despite differing basal rates. This study reveals age-independent sepsis effects on muscle protein synthesis and breakdown.
Area of Science:
- Biochemistry
- Physiology
- Developmental Biology
Background:
- Sepsis significantly alters whole-body protein metabolism.
- Age-related differences in muscle protein turnover are well-documented.
- The impact of sepsis on muscle protein metabolism across different age groups remains unclear.
Purpose of the Study:
- To compare the effects of sepsis on muscle protein metabolism in infant and adult rats.
- To investigate age-dependent responses to sepsis in skeletal muscle.
Main Methods:
- Sepsis was induced using cecal ligation and puncture (CLP) in infant and adult rats.
- Muscle protein synthesis and breakdown rates were measured using radiolabeled tracers (3H-phenylalanine, tyrosine, 3-methylhistidine).
- Metabolic studies were conducted on extensor digitorum longus muscles 16 hours post-CLP.
Main Results:
- Infant rats exhibited higher basal rates of protein synthesis and breakdown compared to adults.
- Sepsis similarly decreased protein synthesis by ~30% in both age groups.
- Sepsis increased total protein breakdown by 40-50% and myofibrillar breakdown severalfold in both infant and adult rats.
Conclusions:
- Despite significant differences in basal muscle protein turnover, sepsis exerts comparable relative effects on protein synthesis and breakdown in infant and adult rats.
- The response of muscle protein metabolism to sepsis is not age-dependent in rats.
- These findings highlight conserved molecular pathways responding to sepsis across developmental stages.
Abstract:
In this study we compared the effect of sepsis on muscle protein metabolism in infant (3 to 4 weeks) and adult (3 to 4 months) rats. Sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent sham operation. Sixteen hours after CLP or sham operation, metabolic studies were performed in incubated intact extensor digitorum longus muscles from infant rats or in strips of the same muscle from adult rats. Protein synthesis rate was determined as incorporation of 3H-phenylalanine into protein; total and myofibrillar protein breakdown rates were determined as release of tyrosine and 3-methylhistidine, respectively. Mortality rate following CLP was similar in both age groups. Basal protein synthesis rate was 3 times higher, total protein breakdown rate was 50% higher, and myofibrillar protein breakdown rate was 3 times higher in infant than in adult animals. However, the relative changes in protein turnover rates induced by sepsis were similar in infant and adult rats: protein synthesis rate decreased by approximately 30%, total protein breakdown increased by 40% to 50%, and myofibrillar protein breakdown increased severalfold. The data suggest that despite prominent differences in basal protein turnover rates between infant and adult rats, the effect of sepsis on muscle protein metabolism is not age dependent.