title: Deletion of the gene encoding MyD88 protects from anorexia in a mouse tumor model.
abstract: The anorexia-cachexia syndrome, characterized by a rise in energy expenditure and loss of body weight that paradoxically are associated with loss of appetite and decreased food intake, contributes significantly to the morbidity and mortality in cancer. While the pathophysiology of cancer anorexia-cachexia is poorly understood, evidence indicates that pro-inflammatory cytokines are key mediators of this response. Although inflammation hence is recognized as an important component of cancer anorexia-cachexia, the molecular pathways involved are largely unknown. We addressed this issue in mice carrying a deletion of the gene encoding MyD88, the key intracellular adaptor molecule in Toll-like and interleukin-1 family receptor signaling. Wild-type and MyD88-deficient mice were transplanted subcutaneously with a syngenic methylcholanthrene-induced tumor (MCG 101) and daily food intake and body weight were recorded. Wild-type mice showed progressively reduced food intake from about 5days after tumor transplantation and displayed a slight body weight loss after 10days when the experiment was terminated. In contrast, MyD88-deficient mice did not develop anorexia, and displayed a positive body weight development during the observation period. While the MyD88-deficient mice on average developed somewhat smaller tumors than wild-type mice, this did not explain the absence of anorexia, because anorexia was seen in wild-type mice with similar tumor mass as non-anorexic knock-out mice. These data suggest that MyD88-dependent mechanisms are involved in the metabolic derangement during cancer anorexia-cachexia and that innate immune signaling is important for the development of this syndrome.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ruud
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
authors.forename: David
authors.initials: D
authors.lastname: Engblom
authors.forename: Anders
authors.initials: A
authors.lastname: Blomqvist
mesh_terms: D000818:Animals; D000855:Anorexia / Q000276:immunology* / Q000503:physiopathology*; D001066:Appetite / Q000276:immunology; D001835:Body Weight / Q000276:immunology*; D002100:Cachexia / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D004435:Eating / Q000276:immunology*; D005260:Female; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics*; D009369:Neoplasms / Q000503:physiopathology*; D017384:Sequence Deletion; D013577:Syndrome; D014185:Transplantation, Isogeneic; D015431:Weight Loss / Q000276:immunology
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D008748:Methylcholanthrene