Morphology, metabolism, microcirculation, and strength of skeletal muscles in cancer-related cachexia

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

“…Increased expression of genes related to fatty acid utilization and the absence of lipid accumulation in liver and quadriceps muscle suggests fatty acids were effectively oxidized to meet energy demands in these tissues. This contrasts with findings in humans where significant intramyocellular lipid accumulation occurs in later stages of cachexia 29,39 which has been speculated to be a consequence of alterations to mitochondrial oxidative capacity found in advanced states of cachexia. 28 That ubiquitin-proteosome-dependent proteolysis is an ATPconsuming process may explain the increased expression of markers of lipid uptake and utilization in muscle in early cachexia when proteolysis, accompanied by anorexia, commences.…”

“…6,[11][12][13][14]37,38 Mechanistic studies suggest PKA-induced lipolysis is not enhanced in late stage cachexia; 38 instead, increased expression of lipases may be responsible for lipid catabolism in adipose tissue in these more advanced stages of cachexia. 13,38 Studies have also reported enhanced lipid accumulation in muscle in cachectic patients with increased weight loss 29,39 and hepatic steatosis in fully-established cachexia in experimental tumor-bearing animals. 26,30 Lipid metabolism in early cachexia, when weight loss is less severe, has been minimally studied.…”

“…Consistent with these studies, a gene expression profile of subcutaneous adipose tissue comparing cachectic cancer patients (»10% weight loss) to weight-stable cancer patients demonstrated genes related to fatty acid degradation and oxidative capacity were more highly expressed in cachectic patients and coincided with elevated levels of whole body fatty acid oxidation. 18 While studies of adipose tissue suggest lipolysis and oxidation of fatty acids within adipocytes may be enhanced in later stages of cachexia, studies of liver and muscle tissue suggest there is a reduction in fatty acid oxidation/oxidative capacity in hepatocytes [25][26][27] and myocytes 28 and consequently, lipid accumulation in these tissues 26,29,30 in more advanced stages of cachexia. To our knowledge, studies of lipid metabolism in adipose, liver and muscle tissues have not been reported for early stages of cachexia when weight loss is less than 10% of initial body weight and adipose tissue loss is significant, but not severe.…”

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

“…The improved physical performance coincided with increased BW and appetite . Next to muscle massdependent changes in muscle function, as described by Weber et al (2008), also muscle mass-independent loss of function is suggested by presented data (Figures 2D and 3D). A tumour-related, muscle mass-independent decrease in muscle function has not been described before.…”

“…A tumour-related, muscle mass-independent decrease in muscle function has not been described before. Weber et al (2008) described in humans that cachexia is associated with a loss of muscle volume, but not of functionality. It might be that the technique used in this study is more accurate because muscles can be weighed instead of being estimated, which might result in less variation in the results.…”