Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia

Michelle L. Asp, Min Tian, Kara L. Kliewer, Martha A. Belury

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)957-965
Number of pages9
JournalCancer Biology and Therapy
Volume12
Issue number11
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Donna McCarthy and Michael Stout for helpful discussion and contributions to necropsy. This research was supported by the Carol S. Kennedy Endowment (M.A.B.), the Ohio Agricultural Research and Development Center (M.A.B.), and the P.E.O. Scholar Award (M.L.A).

Keywords

  • Cancer cachexia
  • Colon-26 adenocarcinoma
  • Insulin resistance
  • Rosiglitazone

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