Intramyocellular lipid droplets increase with progression of cachexia in cancer patients

Abstract

BACKGROUND: Intramyocellular lipids are an important source of fuel for mitochondrial fat oxidation and play an important role in intramuscular lipid homeostasis. We hypothesised that due to the phenotype associated with cancer cachexia, there would exist an association between increasing weight loss and the number/size of intramyocellular lipid droplets. METHODS: Nineteen cancer patients and 6 controls undergoing surgery were recruited. A rectus abdominis biopsy was performed and processed for transmission electron microscopy (TEM). The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images. CT scans, performed as part of patients' routine care, were analysed to determine amount of adipose (intermuscular, visceral and subcutaneous) and muscle tissue. RESULTS: Compared with controls, cancer patients had increased numbers of lipid droplets (mean (SD) 1.8 (1.9) vs. 6.4 (9.1) per ×2,650 field, respectively, p = 0.036). Mean (SD) lipid droplet diameter was also higher in cancer patients compared with controls (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015). Mean lipid droplet count correlated positively with the severity of weight loss (R = 0.51, p = 0.025) and negatively with CT-derived measures of intermuscular fat (R = -0.53, p = 0.022) and visceral fat (R = -0.51, p = 0.029). CONCLUSIONS: This study suggests that the number and size of intramyocellular lipid droplets is increased in the presence of cancer and increases further with weight loss/loss of adipose mass in other body compartments.

Fig. 1

Representative electron micrographs for controls and cancer patients. a. Images are all at ×2,650 magnification. Greater numbers of lipid droplets (white vacuoles) were evident with increasing weight loss. Percent (%) values for cancer patients refer to weight change from pre-illness stable weight. Bars represent 2 μm. b. ×11,000 magnification image of a lipid droplet demonstrating the absence of double membranes, thus distinguishing it from vacuolated giant mitochondria [36]

Fig. 2

Percentage weight loss versus lipid droplet number. There was a significant positive correlation between percentage weight loss and LD number (R = 0.51, p = 0.025; Pearson's correlation, two tailed). There was no significant difference in LD number according to tumour site (one-way ANOVA, p = 0.559). LD lipid droplet