Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared with normal birth weight

• Published in: European journal of endocrinology Vol. 167; no. 6; pp. 829 - 838
• Main Authors: Friedrichsen, Martin, Ribel-Madsen, Rasmus, Mortensen, Brynjulf, Hansen, Christina N, Alibegovic, Amra C, Højbjerre, Lise, Sonne, Mette P, Wojtaszewski, Jørgen F P, Stallknecht, Bente, Dela, Flemming, Vaag, Allan
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.12.2012
• Subjects: Adult; Antigens, CD - genetics; Antigens, Differentiation, Myelomonocytic - genetics; Biological and medical sciences; Carrier Proteins - genetics; Chemokine CCL2 - genetics; Clinical Study; Diseases of mother, fetus and pregnancy; Electron Transport Complex IV - genetics; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Gynecology. Andrology. Obstetrics; Humans; Infant, Low Birth Weight; Infant, Newborn; Interleukin-6 - genetics; Male; Medical sciences; Muscle, Skeletal - metabolism; NADH, NADPH Oxidoreductases - genetics; NF-kappa B - metabolism; Pregnancy. Fetus. Placenta; Rest - physiology; Signal Transduction - physiology; Vertebrates: endocrinology; Young Adult; Human; Physical exercise; Pregnancy disorders; Low birth weight; Male; Inflammation; Normal; Newborn diseases; Prematurity; Young adult; Muscle; Endocrinology; Comparative study
• ISSN: 0804-4643; 1479-683X; 1479-683X
• DOI: 10.1530/EJE-12-0498

ObjectiveThe molecular mechanisms linking physical inactivity and muscle insulin resistance in humans have been suggested to include increased muscle inflammation, possibly associated with impaired oxidative metabolism. We employed a human bed rest study including 20 young males with normal birth weight (NBW) and 20 with low birth weight (LBW) and increased risk of diabetes.MethodologyThe subjects were studied before and after 9 days of bed rest using the euglycemic–hyperinsulinemic clamp and muscle biopsy excision. Muscle inflammatory status was assessed as nuclear factor-κB (NF-κB) activity and mRNA expression of the pro-inflammatory MCP1 (CCL2) and IL6 and the macrophage marker CD68. Furthermore, mRNA expression of genes central to oxidative phosphorylation (OXPHOS) was measured including ATP5O, COX7A1, NDUFB6, and UQCRB.ResultsAt baseline, muscle inflammatory status was similar in NBW and LBW individuals. After bed rest, CD68 expression was increased in LBW (P=0.03) but not in NBW individuals. Furthermore, expression levels of all OXPHOS genes were reduced after bed rest in LBW (P≤0.05) but not in NBW subjects and were negatively correlated with CD68 expression in LBW subjects (P≤0.03 for all correlations). MCP1 expression and NF-κB activity were unaffected by bed rest, and IL6 expression was too low for accurate measurements. None of the inflammatory markers correlated with insulin sensitivity.ConclusionsAlthough LBW subjects exhibit disproportionately elevated CD68 mRNA expression suggesting macrophage infiltration and reduced OXPHOS gene expression when exposed to bed rest, our data altogether do not support the notion that bed rest-induced (9 days) insulin resistance is caused by increased muscle inflammation.