Kevin D Hall1, Vickie E Baracos. 1. Laboratory of Biological Modeling, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-5621, USA. kevinh@niddk.nih.gov
Abstract
PURPOSE OF REVIEW: Measurements of whole-body energy expenditure, body composition, and in-vivo metabolic fluxes are required to quantitatively understand involuntary weight loss in cancer cachexia. Such studies are rare because cancer cachexia occurs near the end of life when invasive metabolic tests may be precluded. Thus, models of cancer-associated weight loss are an important tool for helping to understand this debilitating condition. RECENT FINDINGS: A computational model of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to semi-starvation and re-feeding. Here, this model was used to integrate data on the metabolic changes in patients with cancer cachexia. The resulting computer simulations show how the known metabolic disturbances synergize with reduced energy intake to result in a progressive loss of body weight, fat mass, and fat-free mass. The model was also used to simulate the effects of nutritional support and investigate inhibition of lipolysis versus proteolysis as potential therapeutic approaches for cancer cachexia. SUMMARY: Computational modeling is a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provide a conceptual framework to help understand involuntary weight loss and predict the effects of potential therapies.
PURPOSE OF REVIEW: Measurements of whole-body energy expenditure, body composition, and in-vivo metabolic fluxes are required to quantitatively understand involuntary weight loss in cancer cachexia. Such studies are rare because cancer cachexia occurs near the end of life when invasive metabolic tests may be precluded. Thus, models of cancer-associated weight loss are an important tool for helping to understand this debilitating condition. RECENT FINDINGS: A computational model of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to semi-starvation and re-feeding. Here, this model was used to integrate data on the metabolic changes in patients with cancer cachexia. The resulting computer simulations show how the known metabolic disturbances synergize with reduced energy intake to result in a progressive loss of body weight, fat mass, and fat-free mass. The model was also used to simulate the effects of nutritional support and investigate inhibition of lipolysis versus proteolysis as potential therapeutic approaches for cancer cachexia. SUMMARY: Computational modeling is a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provide a conceptual framework to help understand involuntary weight loss and predict the effects of potential therapies.
Authors: K C Fearon; D T Hansell; T Preston; J A Plumb; J Davies; D Shapiro; A Shenkin; K C Calman; H J Burns Journal: Cancer Res Date: 1988-05-01 Impact factor: 12.701
Authors: W D Dewys; C Begg; P T Lavin; P R Band; J M Bennett; J R Bertino; M H Cohen; H O Douglass; P F Engstrom; E Z Ezdinli; J Horton; G J Johnson; C G Moertel; M M Oken; C Perlia; C Rosenbaum; M N Silverstein; R T Skeel; R W Sponzo; D C Tormey Journal: Am J Med Date: 1980-10 Impact factor: 4.965
Authors: Jessica R Lieffers; Marina Mourtzakis; Kevin D Hall; Linda J McCargar; Carla M M Prado; Vickie E Baracos Journal: Am J Clin Nutr Date: 2009-02-25 Impact factor: 7.045
Authors: Albert A de Graaf; Andreas P Freidig; Baukje De Roos; Neema Jamshidi; Matthias Heinemann; Johan A C Rullmann; Kevin D Hall; Martin Adiels; Ben van Ommen Journal: PLoS Comput Biol Date: 2009-11-26 Impact factor: 4.475