Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia

Katja Trobec, Sandra Palus, Anika Tschirner, Stephan von Haehling, Wolfram Doehner, Mitja Lainscak, Stefan D. Anker, Jochen Springer

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1069-1075
Number of pages7
JournalNutrition
Volume30
Issue number9
DOIs
Publication statusPublished - 2014

Fingerprint

rosiglitazone
Cachexia
Survival
Neoplasms
Skeletal Muscle
Body Composition
Weight Loss
Placebos
Proteasome Endopeptidase Complex
Survival Analysis
Cardiac Output
Stroke Volume
Trypsin
Type 2 Diabetes Mellitus

Keywords

  • Body composition
  • Echocardiography
  • Glitazone
  • Proteasome
  • Survival
  • Thiazolidinedione
  • Wasting

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Medicine(all)

Cite this

Trobec, K., Palus, S., Tschirner, A., von Haehling, S., Doehner, W., Lainscak, M., ... Springer, J. (2014). Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia. Nutrition, 30(9), 1069-1075. https://doi.org/10.1016/j.nut.2013.12.005

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 journalArticle

Trobec, K, Palus, S, Tschirner, A, von Haehling, S, Doehner, W, Lainscak, M, Anker, SD & Springer, J 2014, 'Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia', Nutrition, vol. 30, no. 9, pp. 1069-1075. https://doi.org/10.1016/j.nut.2013.12.005
Trobec K, Palus S, Tschirner A, von Haehling S, Doehner W, Lainscak M et al. Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia. Nutrition. 2014;30(9):1069-1075. https://doi.org/10.1016/j.nut.2013.12.005
Trobec, Katja ; Palus, Sandra ; Tschirner, Anika ; von Haehling, Stephan ; Doehner, Wolfram ; Lainscak, Mitja ; Anker, Stefan D. ; Springer, Jochen. / Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia. In: Nutrition. 2014 ; Vol. 30, No. 9. pp. 1069-1075.
@article{6d48578e272b43fbabacb9cafdc3b12b,
title = "Rosiglitazone reduces body wasting and improves survival in a rat model of cancer cachexia",
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.",
keywords = "Body composition, Echocardiography, Glitazone, Proteasome, Survival, Thiazolidinedione, Wasting",
author = "Katja Trobec and Sandra Palus and Anika Tschirner and {von Haehling}, Stephan and Wolfram Doehner and Mitja Lainscak and Anker, {Stefan D.} and Jochen Springer",
year = "2014",
doi = "10.1016/j.nut.2013.12.005",
language = "English",
volume = "30",
pages = "1069--1075",
journal = "Nutrition International",
issn = "0899-9007",
publisher = "Elsevier Inc.",
number = "9",

}

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 -