Background
Patients with pancreatic ductal adenocarcinoma (PDAC) have low survival rates, in part due to the high incidence of cancer cachexia, a complex metabolic disorder characterized by rapid involuntary weight loss of skeletal muscle and adipose tissue [1, 2]. Atrophy of skeletal muscle is induced by metabolic changes that activate catabolic pathways, resulting in protein degradation and loss of muscle mass [3, 4]. Adipose tissue degradation appears likely due to the actions of the secretory products of adipose tissue, lipolysis and thermogenesis [5-8]. Interestingly, white adipose tissue browning is detectable in the pre-cachectic state, prior to body weight and skeletal muscle loss [7]. A reliable method is critically needed to analyse these complex interactions at the onset and progression of cancer cachexia. Therefore, we aimed to optimise the use of Dual-energy X-ray absorptiometry (DEXA) to evaluate lean and fat mass loss in an established mouse model of cancer cachexia.
Methods
Using DEXA, body composition was analysed in male C57Bl/6 mice, either PBS treated (n=4) or PDAC treated (n=7) through scans at baseline, and at five subsequent timepoints. Muscle mass was measured in the hindlimbs while the abdominal cavity was used to analyse tumour progression. Post-mortem measurement of skeletal muscle weight was conducted. Statistical analysis was performed using unpaired t-tests.
Results
At endpoint, fat and body mass were significantly decreased in tumour-bearing mice compared to controls (p<0.05) while there was no difference in lean mass. The hindlimbs of tumour-bearing mice displayed a similar decrease in fat mass (p<0.05) but no difference in lean mass. Conversely, post-mortem weight of the hindlimbs was decreased in both the TA (p<0.01) and gastrocnemius with plantaris (p<0.05).
Conclusions
DEXA can accurately measure body composition, however the onset of cachexia as evaluated by skeletal muscle loss may not be accurately predicted through this method.