Adiponectin and Tibialis Anterior Mass Are Increased in Cachectic Tumor-Bearing Mice by Rosiglitazone
Creators:Combs, Bethanie A.
Advisor:Belury, Martha A.
Contributors:Wendel, Angela A.
Guttridge, Denis C.
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Series/Report no.:Human Nutrition. Graduate student poster competition, 2006
Cachexia is a disorder characterized by extreme adipose and muscle loss. Insulin resistance is a characteristic of cachexia, which affects nearly eighty percent of all colon cancer patients. The purpose of this pilot study was to determine the extent that rosiglitazone can alter muscle mass in a murine model for colon cancer cachexia. Rosiglitazone sensitizes peripheral tissues to insulin by activating peroxisome proliferator-activated receptor gamma (PPARγ). Treatment with rosiglitazone increases serum adiponectin levels through the activation of PPARγ. Improved insulin sensitivity should increase glucose uptake into muscle, therefore we hypothesize that treatment with rosiglitazone: 1) increases muscle mass when administered to CD2F1 mice bearing colon – 26adenocarcinoma; and 2) increases serum adiponectin levels. Male CD2F1 mice were divided into two groups and treated daily with rosiglitazone (10mg/kg BW) or phosphate buffered saline (PBS) via intraperitoneal injection. After two weeks of treatment mice were inoculated with C26adenocarcinoma. Three weeks post tumor inoculation, necropsies were performed and liver, gastrocnemius, quadriceps, and tibialis anterior of the right hind limb were snap frozen in liquid nitrogen and later weighed by top loading balance. Mass of the tibialis anterior was significantly elevated in mice treated with rosiglitazone compared to mice treated with PBS (p<0.05). Serum adiponectin was significantly elevated in rosiglitazone treated mice (p<0.05) as well. These findings suggest that rosiglitazone may elevate muscle mass in a murine cancer cachexia model through increased serum adiponectin. Further work is needed to determine the mechanism of rosiglitazone to sustain muscle, modulate metabolism, and preserve adiponectin levels under the condition of cachexia.
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