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Intramyocellular lipid droplets increase with progression of cachexia in cancer patients.

Stephens NA, Skipworth RJ, Macdonald AJ, Greig CA, Ross JA, Fearon KC - J Cachexia Sarcopenia Muscle (2011)

Bottom Line: 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.The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences and Community Health, University of Edinburgh, Royal Infirmary, 51 Little France Crescent, Edinburgh, EH16 4SA UK.

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.

No MeSH data available.


Related in: MedlinePlus

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]
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Fig1: 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]

Mentions: Nineteen cancer patients (11 men, 8 women) and 6 controls (2 men, 4 women) were recruited. Demographics are shown in Table 1. Eight patients had pancreatic cancer, four gastric, three oesophageal, three oesophagogastric junctions and one patient with small bowel cancer. The mean body mass index (BMI) of both the cancer patient and control groups was >25. Cancer patients were older than controls (mean age (standard deviation) 67 (10) vs. 53 (8) years, respectively, p = 0.005) and had a significantly higher percentage weight loss (6.0% (7.1%) vs. −0.3% (1.4%), respectively, p = 0.002). Mid-arm muscle circumference (MAMC) and arm muscle cross-sectional area (CSA) were not significantly different between controls and cancer patients. There was a trend towards higher Karnofsky performance scores in controls compared with cancer patients (98.3 (3.1) vs. 91.7 (8.6), p = 0.083). Significantly more cancer patients exhibited systemic inflammation (C-reactive protein (CRP) ≥5 mg/l) than controls (n = 11/19 vs. 0/6, respectively, p = 0.020 Fisher's exact test). Both the average lipid droplet number (6.4 (9.1) vs. 1.8 (1.9), p = 0.036, see also Fig. 1) and the average lipid droplet diameter (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015) were higher in the cancer cohort compared with controls.Table 1


Intramyocellular lipid droplets increase with progression of cachexia in cancer patients.

Stephens NA, Skipworth RJ, Macdonald AJ, Greig CA, Ross JA, Fearon KC - J Cachexia Sarcopenia Muscle (2011)

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]
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Related In: Results  -  Collection

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Fig1: 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]
Mentions: Nineteen cancer patients (11 men, 8 women) and 6 controls (2 men, 4 women) were recruited. Demographics are shown in Table 1. Eight patients had pancreatic cancer, four gastric, three oesophageal, three oesophagogastric junctions and one patient with small bowel cancer. The mean body mass index (BMI) of both the cancer patient and control groups was >25. Cancer patients were older than controls (mean age (standard deviation) 67 (10) vs. 53 (8) years, respectively, p = 0.005) and had a significantly higher percentage weight loss (6.0% (7.1%) vs. −0.3% (1.4%), respectively, p = 0.002). Mid-arm muscle circumference (MAMC) and arm muscle cross-sectional area (CSA) were not significantly different between controls and cancer patients. There was a trend towards higher Karnofsky performance scores in controls compared with cancer patients (98.3 (3.1) vs. 91.7 (8.6), p = 0.083). Significantly more cancer patients exhibited systemic inflammation (C-reactive protein (CRP) ≥5 mg/l) than controls (n = 11/19 vs. 0/6, respectively, p = 0.020 Fisher's exact test). Both the average lipid droplet number (6.4 (9.1) vs. 1.8 (1.9), p = 0.036, see also Fig. 1) and the average lipid droplet diameter (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015) were higher in the cancer cohort compared with controls.Table 1

Bottom Line: 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.The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Surgical Sciences (Surgery), School of Clinical Sciences and Community Health, University of Edinburgh, Royal Infirmary, 51 Little France Crescent, Edinburgh, EH16 4SA UK.

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.

No MeSH data available.


Related in: MedlinePlus