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

Martin Friedrichsen; Rasmus Ribel-Madsen; Brynjulf Mortensen; Christina Neigaard Hansen; Amra C Alibegovic; Lise Højbjerre; Mette Paulli Sonne; Jørgen Wojtaszewski; Bente Stallknecht; Flemming Dela; Allan Vaag

doi:10.1530/eje-12-0498

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

Martin Friedrichsen, Rasmus Ribel-Madsen, Brynjulf Mortensen, Christina Neigaard Hansen, Amra C Alibegovic, Lise Højbjerre, Mette Paulli Sonne, Jørgen Wojtaszewski, Bente Stallknecht, Flemming Dela, Allan Vaag

11 Citations (Scopus)

Abstract

Objective: The 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. Methodology: The 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. Results: At 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. Conclusions: Although 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.

Original language	English
Journal	European Journal of Endocrinology
Volume	167
Issue number	6
Pages (from-to)	829-838
Number of pages	10
ISSN	0804-4643
DOIs	https://doi.org/10.1530/eje-12-0498
Publication status	Published - Dec 2012

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Friedrichsen, M., Ribel-Madsen, R., Mortensen, B., Hansen, C. N., Alibegovic, A. C., Højbjerre, L., Sonne, M. P., Wojtaszewski, J., Stallknecht, B., Dela, F., & Vaag, A. (2012). Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared to normal birth weight. European Journal of Endocrinology, 167(6), 829-838. https://doi.org/10.1530/eje-12-0498

Friedrichsen, M, Ribel-Madsen, R, Mortensen, B, Hansen, CN, Alibegovic, AC, Højbjerre, L, Sonne, MP, Wojtaszewski, J , Stallknecht, B , Dela, F & Vaag, A 2012, 'Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared to normal birth weight', European Journal of Endocrinology, vol. 167, no. 6, pp. 829-838. https://doi.org/10.1530/eje-12-0498

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

abstract = "Objective: The 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. Methodology: The 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. Results: At 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. Conclusions: Although 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.",

author = "Martin Friedrichsen and Rasmus Ribel-Madsen and Brynjulf Mortensen and Hansen, {Christina Neigaard} and Alibegovic, {Amra C} and Lise H{\o}jbjerre and Sonne, {Mette Paulli} and J{\o}rgen Wojtaszewski and Bente Stallknecht and Flemming Dela and Allan Vaag",

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doi = "10.1530/eje-12-0498",

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TY - JOUR

T1 - Muscle inflammatory signaling in response to 9 days of physical inactivity in young men with low compared to normal birth weight

AU - Friedrichsen, Martin

AU - Ribel-Madsen, Rasmus

AU - Mortensen, Brynjulf

AU - Hansen, Christina Neigaard

AU - Alibegovic, Amra C

AU - Højbjerre, Lise

AU - Sonne, Mette Paulli

AU - Wojtaszewski, Jørgen

AU - Stallknecht, Bente

AU - Dela, Flemming

AU - Vaag, Allan

N1 - CURIS 2012 5200 090

PY - 2012/12

Y1 - 2012/12

N2 - Objective: The 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. Methodology: The 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. Results: At 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. Conclusions: Although 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.

AB - Objective: The 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. Methodology: The 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. Results: At 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. Conclusions: Although 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.

U2 - 10.1530/eje-12-0498

DO - 10.1530/eje-12-0498

M3 - Journal article

C2 - 22968485

SN - 0804-4643

VL - 167

SP - 829

EP - 838

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 6

ER -

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

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