A 65-year old patient has colon carcinoma metastatic to the liver and lungs. He has had a weight loss of 10 kg. Cytokine-dependent tumor cachexia is attributable to which of the following?

a. Increased glucose uptake and increased glycogen breakdown occur in this circumstance.

b. Suppressed activity of lipoprotein lipase results from TNFa

c. TNFa stimulates lipolysis

d. The differentiation process of pre-adipocytes is impaired 

e. Partial reversal of differentiated adipocytes to pre-adipocyte morphology and gene expression occurs

Tumor cachexia appears to be mediated by TNFa. Lipopolysaccharide (LPS), as well as other cytokines, activate a variety of inflammatory cells, most importantly macrophages, to produce TNFa. Both the chronic administration of TNFa to rats and implantation of tumors secreting TNFa in mice induce a syndrome of cachexia. In vitro, higher TNFa concentrations alter glucose metabolism in cultured myotubules by increasing glucose uptake and glycogen breakdown. It has also been demonstrated that purified TNFa suppresses lipoprotein lipase activity and stimulates lipolysis in cultured adipocytes. Further, TNFa not only inhibits the differentiation process of preadipocytes, but partially reverses differentiated adipocytes to a preadipocyte morphology and pattern of gene expression. All of these metabolic effects at least partially explain the chronic syndromes of anorexia, weight loss, and cachexia that are associated with both chronic infection and malignancy.