title: Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia.
abstract: Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia.
authors: Department of Human Nutrition, Ohio State University, Columbus, USA.
authors: Michelle L
authors: ML
authors: Asp
authors: Min
authors: M
authors: Tian
authors: Kara L
authors: KL
authors: Kliewer
authors: Martha A
authors: MA
authors: Belury
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D000855:Anorexia / Q000188:drug therapy*; D001786:Blood Glucose / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D004435:Eating / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D007333:Insulin Resistance; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D009929:Organ Size; D059748:Proteolysis / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone