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
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.
