Serum metabolic profiles reveal the effect of formoterol on cachexia in tumor-bearing mice.
Cancer cachexia is a complex metabolic syndrome that cannot be fully reversed by conventional nutritional support, and leads to the progressive wasting of body tissues, particularly the loss of lean muscle mass. Formoterol, a highly selective β2-adrenoceptor therapeutic drug, gives potential anabolic responses in the context of skeletal muscles and was widely confirmed to possess anti-cachexia effects. However, the possible metabolic pathways and the metabolite changes that initiate and maintain these anabolic responses remain poorly understood. In the present study, a (1)H NMR-metabonomics model was established to investigate the metabolic features of cancer cachexia and the contribution of formoterol to serum metabolites in a mouse model bearing CT26 carcinoma cells. Among the metabolic processes found in serum, the ones associated with cancer are glycolysis and lipid lipolysis. However, the citrate cycle and amino acid metabolism are the major metabolic characteristics of cachexia. Furthermore, formoterol stimulated skeletal muscle growth, increased the body weight and altered the metabolic profile. Amino acids, ketone bodies and citrate cycle metabolites are potential biomarkers associated with these functional pathways. Taking the pathways of cancer cachexia into account, formoterol could regulate the imbalance in glycolysis, the citrate cycle, and in lipid and amino acid metabolism. Collectively, these results indicate that formoterol partially reverses the metabolic disturbances associated with cachexia.
Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, No. 600, Road Yishan, Shanghai 200233, P. R. China. guoc66@gmail.com.
Yang
Y
Quanjun
Yang
Y
Genjin
Wan
W
Lili
Li
L
Bin
Lu
L
Jin
Yu
Y
Qi
Li
L
Yan
Han
H
Yonglong
Guo
G
Cheng
Zhang
Z
Junping
D000818:Animals; D002100:Cachexia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006019:Glycolysis / Q000187:drug effects; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy*
D004983:Ethanolamines; D000068759:Formoterol Fumarate