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| L-carnitine inhibits skeletal muscle atrophy in cancer cachexia via the AMPK/ mTOR/ FOXO1 signaling pathway |
| Wang Li, Tong Ning, Huo Zhenyu, Lu Zongliang, Li Na, Xu Hongxia |
| Department of Clinical Nutrition Daping Hospital Army Medical University Third Military Medical University Chongqing Municipal
Health Commission Key Laboratory of Intelligent Clinical Nutrition and Transformation Chongqing 400042 China |
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Abstract Objective This study aimed to elucidate the role of the AMPK signaling pathway in interleukin-6 IL-6 -induced
skeletal muscle atrophy and to evaluate the inhibitory effect of L-carnitine LC on tumor cachexia-induced skeletal muscle atrophy
as well as whether this effect is mediated through the AMPK signaling pathway. Method C2C12 myoblasts were induced to atrophy with
200 ng / ml IL-6 to establish an in vitro cellular model of tumor cachexia-induced skeletal muscle decline. The experiment was divided
into control group IL-6 group and IL-6+LC treatment group to observe the effects of LC on the prevention and treatment of tumor
cachexia-induced skeletal muscle atrophy C2C12 cells were stained with crystal violet to assess the effect of LC on myotube atrophy
RT-PCR was used to detect the transcription levels of p70S6K MuRF1 and Atrogin - 1 to assess the effect of LC on tumor
cachexia-induced skeletal muscle decline Western blot analysis was used to examine the expression and phosphorylation levels of
AMPK/ mTOR/ FOXO1 signaling pathway proteins in C2C12 cells to explore the possible mechanism by which LC alleviates IL- 6-
induced skeletal muscle decline. An in vivo tumor cachexia model was established by intraperitoneal injection of colon cancer MC38
cells in 8-week-old C57 mice. The experiment was divided into MC38+LC group and MC38+ddH2O group with daily intragastric
administration of 5 mg / kg LC or an equivalent volume of ddH2O. The mice's physical fitness muscle strength and serum IL-6
levels were tested by open field test grip strength test and ELISA respectively. Result In vitro compared to the control group the
IL-6 group showed a reduction in myotube diameter P< 0. 05 upregulation of MuRF1 and Atrogin- 1 transcriptional levels P<0. 05 increased phosphorylation of AMPK P<0. 05 and decreased phosphorylation of mTOR p70S6K and FOXO1 P<0. 05
with LC reversing these effects. In vivo mice in the MC38+LC group exhibited increased movement distance 178. 29% P<0. 05
enhanced muscle strength 62. 74% P< 0. 05 and lower serum IL - 6 levels P< 0. 05 compared to the MC38 + ddH2O group.
Conclusion L-carnitine may inhibit interleukin-6-induced tumor cachexia skeletal muscle decline through the AMPK/ mTOR/ FOXO1
signaling pathway.
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