title: Physiological characterization of a mouse model of cachexia in colorectal liver metastases.
abstract: Loss of skeletal muscle mass and function (cachexia) is severe in patients with colorectal liver metastases because of the large increase in resting energy expenditure but remains understudied because of a lack of suitable preclinical models. Our aim was to characterize a novel preclinical model of cachexia in colorectal liver metastases. We tested the hypothesis that mice with colorectal liver metastases would exhibit cachexia, as evidenced by a reduction in liver-free body mass, muscle mass, and physiological impairment. Twelve-week-old male CBA mice received an intrasplenic injection of Ringer solution (sham) or murine colorectal cancer cells (MoCR) to induce colorectal liver metastases. At end-point (20-29 days), the livers of MoCR mice were infiltrated completely with metastases, and MoCR mice had reduced liver-free body mass, muscle mass, and epididymal fat mass compared with sham controls (P < 0.03). MoCR mice exhibited impaired rotarod performance and grip strength (P < 0.03). Histochemical analyses of tibialis anterior muscles from MoCR mice revealed muscle fiber atrophy and reduced oxidative enzyme activity (P < 0.001). Adipose tissue remodeling was evident in MoCR mice, with reduced adipocyte diameter and greater infiltration of nonadipocyte tissue (P < 0.05). These findings reveal the MoCR mouse model exhibits significant cachexia and is a suitable preclinical model of cachexia in colorectal liver metastases. This model should be used for identifying effective treatments for cachexia to improve quality of life and reduce mortality in patients with colorectal liver metastases.
authors.affiliation: Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria, Australia. ktmurphy@unimelb.edu.au
authors.forename: Kate T
authors.initials: KT
authors.lastname: Murphy
authors.forename: Adam
authors.initials: A
authors.lastname: Struk
authors.forename: Cathy
authors.initials: C
authors.lastname: Malcontenti-Wilson
authors.forename: Christopher
authors.initials: C
authors.lastname: Christophi
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Lynch
mesh_terms: D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002277:Carcinoma / Q000150:complications* / Q000503:physiopathology / Q000556:secondary; D015179:Colorectal Neoplasms / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D018737:Hand Strength / Q000502:physiology; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000150:complications* / Q000503:physiopathology / Q000556:secondary; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D045442:Rotarod Performance Test
keywords: cancer cachexia; colorectal liver metastases; muscle wasting; muscle weakness