Abstract
Objective: Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Methods: Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Results: Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P <0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Conclusions: Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function.
| Original language | English |
|---|---|
| Pages (from-to) | 1069-1075 |
| Number of pages | 7 |
| Journal | Nutrition |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Body composition
- Echocardiography
- Glitazone
- Proteasome
- Survival
- Thiazolidinedione
- Wasting
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
- Medicine(all)
Cite this
Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia. / Trobec, Katja; Palus, Sandra; Tschirner, Anika; von Haehling, Stephan; Doehner, Wolfram; Lainscak, Mitja; Anker, Stefan D.; Springer, Jochen.
In: Nutrition, Vol. 30, No. 9, 2014, p. 1069-1075.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia
AU - Trobec, Katja
AU - Palus, Sandra
AU - Tschirner, Anika
AU - von Haehling, Stephan
AU - Doehner, Wolfram
AU - Lainscak, Mitja
AU - Anker, Stefan D.
AU - Springer, Jochen
PY - 2014
Y1 - 2014
N2 - Objective: Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Methods: Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Results: Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P <0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Conclusions: Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function.
AB - Objective: Rosiglitazone improves insulin sensitivity and promotes weight gain in patients with type 2 diabetes mellitus, which could be useful in wasting and cachexia. However, its effects on cardiac function are controversial. The aim of this study was to investigate the effects of rosiglitazone on body wasting, body composition, cardiac function, and survival in a rat model of cancer cachexia. Methods: Rats were injected with Yoshida AH-130 hepatoma tumor cells and randomized to receive placebo or rosiglitazone 4 mg/kg daily. Treatment started 1 d after tumor inoculation and the rats were sacrificed 14 d thereafter. Body weight and body composition was measured at baseline and after removal of tumor. Echocardiography was performed at baseline and on day 11. At the end of the study, organs were weighed and the proteasome activity in gastrocnemius muscle was measured. Results: Survival analysis showed a significant benefit from treatment with rosiglitazone (hazard ratio = 0.38, 95% confidence interval: 0.15-0.86). Rosiglitazone reduced average daily weight loss (2.33 g/d rosiglitazone versus 3.93 g/d placebo; P <0.05) as a result of both fat and lean mass preservation. It decelerated white and brown tissue wasting, but had no effect on skeletal muscle mass and heart mass. However, peptidyl-glutamyl-protein-hydrolysing and trypsin-like activity in gastrocnemius muscle was significantly reduced by rosiglitazone. Finally, it increased left ventricular ejection fraction, fractional shortening, and systolic volume and improved cardiac output in cachectic cancer rats. Conclusions: Rosiglitazone prevents weight loss and improves survival in a rat model of cancer cachexia. It exerts beneficial effects on cardiac function.
KW - Body composition
KW - Echocardiography
KW - Glitazone
KW - Proteasome
KW - Survival
KW - Thiazolidinedione
KW - Wasting
UR - http://www.scopus.com/inward/record.url?scp=84905566574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905566574&partnerID=8YFLogxK
U2 - 10.1016/j.nut.2013.12.005
DO - 10.1016/j.nut.2013.12.005
M3 - Article
C2 - 24976415
AN - SCOPUS:84905566574
VL - 30
SP - 1069
EP - 1075
JO - Nutrition International
JF - Nutrition International
SN - 0899-9007
IS - 9
ER -