2011年12月6日火曜日

IL-6誘導の悪液質に対する運動効果:マウス

マウスでのIL-6誘導の悪液質に対する運動の効果を検証した論文を紹介します。

Melissa J. Puppa, et al: The effect of exercise on IL-6-induced cachexia in the Apc Min/+ mouse. Journal of Cachexia, Sarcopenia and Muscle, 2011, doi: 10.1007/s13539-011-0047-1

下記のHPで全文見ることができます。

http://www.springerlink.com/content/p7kt828212q763n1/fulltext.pdf

基礎研究なので簡単なコメントのみとさせていただきます。中程度のトレッドミル運動(18m/分で1時間、週6日、傾斜5%)でIL-6誘導の悪液質を改善できるかどうかを、カゴの中の対照群と比較検証しています。結果ですが、対照群ではIL-6を過剰発現させると8%の体重減少を認めましたが、運動で有意に体重減少が少なくなりました。

対照群ではIL-6の過剰発現で空腹時血糖と中性脂肪が高値となりましたが、運動で正常化しました。運動による変化は骨格筋の炎症シグナルが上昇しても生じました。これよりIL-6濃度と独立して中程度の運動はIL-6による悪液質を改善させるという結論です。運動効果はインスリン感受性とエネルギー状態の改善と関連していました。

マウスでの実験ですので、そのままヒトにあてはめることはできません。ただ、IL-6が高値でも有酸素運動が有効ということは、ヒト悪液質でもIL-6やCRPが高値でも有酸素運動が有効な可能性があります。IL-6やCRPが高値の場合、レジスタンストレーニングは禁忌と考えていますが、一定の有酸素運動は行ったほうがよいのかもしれません。要検証ですが。

Abstract
Background Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the ApcMin/+ mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL-6-induced cachexia in the ApcMin/+ mouse has not been investigated. The purpose of this study was to assess the effects of exercise on the development of cachexia in the ApcMin/+ mouse.

Methods Mice were randomly assigned to moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were electroporated with either IL-6-containing or control plasmid into the quadriceps muscle. Mice were killed after 2 weeks of systemic IL-6 overexpression or control treatment.

Results IL-6 overexpression induced an 8% loss in body weight in CC mice, which was significantly attenuated by exercise. IL-6 overexpression in CC mice increased fasting insulin and triglyceride levels, which were normalized by exercise, and associated with increased oxidative capacity, an induction of AKT signaling, and a repression of AMPK signaling in muscle. These exercise-induced changes occurred despite elevated inflammatory signaling in skeletal muscle.

Conclusion We conclude that moderate-intensity exercise can attenuate IL-6-dependent cachexia in ApcMin/+ mice, independent of changes in IL-6 concentration and muscle inflammatory signaling. The exercise effect was associated with improved insulin sensitivity and improved energy status in the muscle.

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