Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care—Correlations with food intake, metabolism, exercise capacity, and hormones

Abstract

BACKGROUNDSeveral investigations that yielded different results in terms of net changes in body composition of weight‐losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross‐sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow‐up measurements in relation to other independent methods for the assessment of metabolism and performance.METHODSFor the current report, the authors evaluated time course changes in body composition (dual‐energy X‐ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4–62 months of follow‐up. The entire cohort comprised 311 patients, ages 68 years ± 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver‐biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types).RESULTSDecreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat‐free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C‐reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin‐like growth factor 1 (IGF‐1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF‐1, insulin, leptin, and ghrelin levels (P < 0.02 – P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF‐1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue.CONCLUSIONSThe current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients. Cancer 2005. © 2005 American Cancer Society.

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.…”

“…During the development of cancer cachexia, a well-characterised loss of both adipose tissue and skeletal muscle occurs (Dahlman et al 2010, Arner 2011. It has been proposed that the former often precedes and is more rapid than the latter (Fouladiun et al 2005). Several factors culminate in loss of adipose tissue, such as 1) increased lipid mobilisation due to enhanced adipocyte lipolysis (Agustsson et al 2007, Ryden et al 2008, Arner 2011, 2) reduced lipogenesis due to decreased lipoprotein lipase activity (Tisdale 2009) and 3) impairment of fat cell turnover, which results in a disruption in the formation and development of adipose tissue (Arner & Spalding 2010).…”

Adipose tissue loss in adjuvant arthritis is associated with a decrease in lipogenesis, but not with an increase in lipolysis

“…It has been suggested that in cancer cachexia, loss of WAT mass is related to anorexia and to a decrease in food intake, whereas skeletal muscle loss is more related with increased proteolysis (Fouladiun et al 2005). This does not seem to be the case in adjuvant arthritis, since pair-fed rats, although they have lower body weight than control ad libitum fed rats, have a relative WAT weight similar to them.…”

Adipose tissue pathways involved in weight loss of cancer cachexia

“…We investigated patients with gastrointestinal cancer who had no evidence of gastrointestinal obstruction, and were either weight stable or with evident cachexia. We focused on adipose tissue as preferential wasting of this tissue is involved in the early stages of disease (Fouladiun et al, 2005). Our primary hypothesis was that changes in pathways involved in the regulation of energy metabolism would accompany loss of adipose tissue in cachexia.…”