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IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia.

Schmidt K, von Haehling S, Doehner W, Palus S, Anker SD, Springer J - J Cachexia Sarcopenia Muscle (2011)

Bottom Line: No effect on fat mass was observed.Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21-0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26-1.74, p = 0.42).CONCLUSION: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model.

View Article: PubMed Central - PubMed

ABSTRACT
BACKGROUND: A hallmark symptom of cancer cachexia is the loss of skeletal muscle. This is at least partially due to a deregulation of the growth hormone/IGF-1 axis and a subsequently impaired protein synthesis in skeletal muscle. Here, we investigated the effect of IGF-1 supplementation in a rat model of cancer cachexia. METHODS: Juvenile rats were inoculated with the Yoshida AH-130 hepatoma and treated once daily with 0.3 mg kg(-1) day(-1) (low dose) or 3 mg kg(-1) day(-1) (high dose) IGF-1 or placebo for a period of maximal 16 days. Body weight and body composition (by NMR) were assessed at baseline and at the end of the study or day of death. Locomotor activity and food intake were assessed at baseline and day 10/11 after tumour inoculation for 24 h. RESULTS: Untreated tumour-bearing rats lost 55.3 ± 2.14 g body weight, which was reduced by low-dose to -39.6 ± 11.1 g (p = 0.0434) and high-dose IGF-1 to -42.7 ± 8.8 g (p = 0.057). Placebo-treated rats lost 41.4 ± 2.0-g lean mass, which was attenuated by low-dose IGF-1 (-28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (-30.9 ± 7.4, p = 0.067). Spontaneous activity and food intake were improved by low-dose IGF-1 only. No effect on fat mass was observed. Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21-0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26-1.74, p = 0.42). CONCLUSION: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model. Moreover, an improved quality of life was observed in these animals. Further experiments using different doses are necessary.

No MeSH data available.


Related in: MedlinePlus

Average loss of body weight (a), lean body mass (b) and fat mass (c). Data were calculated as change per day alive. IGF-1 reduced loss of body weight and lean mass, but had no effect on fat mass. **p < 0.01
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Fig1: Average loss of body weight (a), lean body mass (b) and fat mass (c). Data were calculated as change per day alive. IGF-1 reduced loss of body weight and lean mass, but had no effect on fat mass. **p < 0.01

Mentions: The overall weight loss at the end of the study or day of death was highest in the placebo group (−55.3 ± 2.14 g) and was reduced by both low-dose (−39.6 ± 11.1 g, p = 0.0434) and high-dose IGF-1 (−42.7 ± 8.8 g, p = 0.057). This is also seen when the average weight loss per day alive is calculated (Fig. 1a). As expected, treatment with IGF-1 reduced the wasting of lean body mass, i.e. skeletal muscle. Placebo-treated rats lost 41.4 ± 2.0 g lean mass, which was attenuated by low-dose IGF-1 (−28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (−30.9 ± 7.4, p = 0.067), which is also observed in loss of lean mass per day alive (Fig. 1b). Treatment had no effect on overall loss of fat mass (placebo, −11.5 ± 0.5 g; low-dose IGF-1, −12.4 ± 2 g; high-dose IGF-1, −11.0 ± 1.3 g, all p > 0.1) or the loss of fat mass per day alive (Fig. 1c).Fig. 1


IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia.

Schmidt K, von Haehling S, Doehner W, Palus S, Anker SD, Springer J - J Cachexia Sarcopenia Muscle (2011)

Average loss of body weight (a), lean body mass (b) and fat mass (c). Data were calculated as change per day alive. IGF-1 reduced loss of body weight and lean mass, but had no effect on fat mass. **p < 0.01
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117996&req=5

Fig1: Average loss of body weight (a), lean body mass (b) and fat mass (c). Data were calculated as change per day alive. IGF-1 reduced loss of body weight and lean mass, but had no effect on fat mass. **p < 0.01
Mentions: The overall weight loss at the end of the study or day of death was highest in the placebo group (−55.3 ± 2.14 g) and was reduced by both low-dose (−39.6 ± 11.1 g, p = 0.0434) and high-dose IGF-1 (−42.7 ± 8.8 g, p = 0.057). This is also seen when the average weight loss per day alive is calculated (Fig. 1a). As expected, treatment with IGF-1 reduced the wasting of lean body mass, i.e. skeletal muscle. Placebo-treated rats lost 41.4 ± 2.0 g lean mass, which was attenuated by low-dose IGF-1 (−28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (−30.9 ± 7.4, p = 0.067), which is also observed in loss of lean mass per day alive (Fig. 1b). Treatment had no effect on overall loss of fat mass (placebo, −11.5 ± 0.5 g; low-dose IGF-1, −12.4 ± 2 g; high-dose IGF-1, −11.0 ± 1.3 g, all p > 0.1) or the loss of fat mass per day alive (Fig. 1c).Fig. 1

Bottom Line: No effect on fat mass was observed.Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21-0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26-1.74, p = 0.42).CONCLUSION: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model.

View Article: PubMed Central - PubMed

ABSTRACT
BACKGROUND: A hallmark symptom of cancer cachexia is the loss of skeletal muscle. This is at least partially due to a deregulation of the growth hormone/IGF-1 axis and a subsequently impaired protein synthesis in skeletal muscle. Here, we investigated the effect of IGF-1 supplementation in a rat model of cancer cachexia. METHODS: Juvenile rats were inoculated with the Yoshida AH-130 hepatoma and treated once daily with 0.3 mg kg(-1) day(-1) (low dose) or 3 mg kg(-1) day(-1) (high dose) IGF-1 or placebo for a period of maximal 16 days. Body weight and body composition (by NMR) were assessed at baseline and at the end of the study or day of death. Locomotor activity and food intake were assessed at baseline and day 10/11 after tumour inoculation for 24 h. RESULTS: Untreated tumour-bearing rats lost 55.3 ± 2.14 g body weight, which was reduced by low-dose to -39.6 ± 11.1 g (p = 0.0434) and high-dose IGF-1 to -42.7 ± 8.8 g (p = 0.057). Placebo-treated rats lost 41.4 ± 2.0-g lean mass, which was attenuated by low-dose IGF-1 (-28.8 ± 8.3 g, p = 0.041) and high-dose IGF-1 (-30.9 ± 7.4, p = 0.067). Spontaneous activity and food intake were improved by low-dose IGF-1 only. No effect on fat mass was observed. Low-dose IGF-1 significantly reduced mortality (HR = 0.45, 95%CI = 0.21-0.93, p = 0.0315), whilst the high dose did not reach significance (HR = 0.68, 95%CI = 0.26-1.74, p = 0.42). CONCLUSION: Low-dose IGF-1 reduced mortality and attenuated loss of body weight as well as muscle mass in the Yoshida hepatoma rat model. Moreover, an improved quality of life was observed in these animals. Further experiments using different doses are necessary.

No MeSH data available.


Related in: MedlinePlus