Studies on the lipid metabolism of Walker 256 tumour‐bearing rats during the development of cancer cachexia

Abstract

Aspects of the lipid metabolism of Walker 256 carcinosarcoma‐bearing cachectic rats (TB) were investigated during a 14 day interval of tumour growth. Food intake and body weight of the TB rats were reduced by 18% and 13%, respectively, on day 14, as compared with non‐tumour‐bearing animals. The tumour burden then, corresponded to 19 % of total body weight. The total fat content was not different in the liver, heart, carcass, epididymal (EAT) and retroperitoneal (RPAT) adipose tissues of the two groups. The brown adipose tissue (BAT) and skeletal muscle (gastrocnemius‐SM) of the TB rats had increased levels of fat (23 % and 200 %, respectively). Enteral absorption of 14C‐triolein was decreased in the TB rats, but the liver, heart, and SM of these animals incorporated more radiolabelled lipid than the control animals, while the adipose tissues exhibited a decreased incorporation of radioactivity in relation to controls. More lipid was incorporated into the VLDL fraction secreted by the liver of TB rats, which exhibited a different distribution of the incorporated 14C‐oleate in the various lipid subfractions. Ultrastructural studies showed that the hepatocytes of the TB rats had a greater incidence of lipid droplets in the cytoplasm.

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia

“…Cancer cachexia induces wasting of fat mass that accounts for a large part of the dramatic weight loss observed both in humans (Fouladiun et al 2005, Agustsson et al 2007, Dahlman et al 2010) and in animals (Machado et al 2004, Bing et al 2006, Asp et al 2010, and lipid metabolism is markedly altered (Seelaender et al 1996, Tisdale 2009, Arner 2011. Walker 256-induced cachexia was efficient at eliciting loss of body weight in terms of both absolute and relative weight (percentage of total body mass) of the fat depots, with consequent abnormalities in plasma biochemical profile.…”

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

“…Steatosis 26,30 and reductions in fatty acid oxidation/oxidative capacity 25,27,59 in the liver have been reported in the Walker 256 carcinosarcoma cachexia model when weight loss was substantial. In our study of early cachexia, markers of fatty acid oxidation were increased in liver and measurements of hepatic total lipids were not different among groups.…”

“…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. In the present study, we investigated lipid metabolism in the colon-26 murine model of cancer cachexia at the onset of anorexia and weight loss.…”

“…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.…”

Metabolic and Morphologic Characteristics of Adipose Tissue Associated with the Growth of Malignant Tumors

“…The present study using the rabbit model made it possible to measure changes of lipid metabolism periodically, while studies using rats or mice can observe only a few points. 21,22) This was mainly because there was no noninvasive method available to accurately measure fat levels in small animals. We have successfully established a method of measuring total body fat in rabbits by the TOBEC method.…”