Cancer cachexia is characterized by progressive
weight loss with the depletion of adipose tissue and skeletal muscle. Impaired
fatty acid oxidation mainly resulting from the decrease of
carnitine palmitoyltransferase I and II activities in the liver is an important factor that contributes to
cancer cachexia . Although recent studies suggest a potential application of
L-carnitine in treatment of
cancer cachexia, the underlying mechanisms are unknown. In the present study, we aim to assess the effects of
L-carnitine on the activity and expression of
CPT I and II in the liver of cachectic
cancer mice. Our results show that the inoculation of colon-26
adenocarcinoma cells into mice led to
cancer cachexia characterized by notable decreases in food intake, gastrocnemius muscle and epididymus fat weight. In addition, the
mRNA level and activity of liver
carnitine palmitoyltransferase (
CPT) I and II, and serum levels of free
carnitine and
acetylcarnitine were markedly decreased in cachectic mice, accompanied by marked increases in serum levels of
tumor necrosis factor-alpha (TNF-α) and
interleukin-6 (IL-6). A continuous oral treatment with
L-carnitine at 18 mg/kg per day increased dietary uptake, gastrocnemius muscle weight and epididymus fat weight, increased
blood glucose and
serum albumin levels, and decreased total
cholesterol level in
cancer cachectic mice, but did not affect
tumor growth. These effects of
L-carnitine on
cancer cachexia mice were accompanied by the upregulation of
mRNA level of
CPT I and II and increased
enzyme activity of
CPT I in the liver, as well as the downregulation of serum TNF-α and
IL-6 levels. Moreover, free
carnitine levels were negatively correlated with serum TNF-α or
IL-6 level. These results indicate that
L-carnitine ameliorates
cancer cachexia by regulating serum TNF-α and
IL-6 levels and modulating the expression and activity of
CPT in the liver.