scholarly journals Induction of IL-6 by Cytotoxic Chemotherapy Is Associated With Loss of Lean Body and Fat Mass in Tumor-free Female Mice

2014 ◽  
Vol 17 (5) ◽  
pp. 549-557 ◽  
Author(s):  
Collin R. Elsea ◽  
Janet A. Kneiss ◽  
Lisa J. Wood

Cancer patients treated with cytotoxic chemotherapy experience fatigue and changes in body composition that can impact physical functioning and quality of life during and after treatment. Interleukin-6 (IL-6) is associated with fatigue in cancer survivors and plays an important role in the regulation of body composition. The purpose of the present study was to determine the specific role of IL-6 in cyclophosphamide-doxorubicin-5-fluorouracil (CAF)-induced changes in fatigue, food intake, and body composition using mice lacking IL-6. Female wild-type (WT) and IL-6− /− mice were injected with four cycles of CAF or normal saline (NS) administered at 21-day intervals. Daily voluntary wheel-running activity (VWRA), used as a proxy for fatigue, and food intake were monitored daily up to 21 days after the fourth dose. Dual-energy X-ray absorptiometry (DEXA) was used to assess treatment-related changes in lean body mass (LBM), fat mass (FM), and bone mineral content (BMC). Patterns of change in fatigue and food intake did not differ between CAF-treated WT and IL-6− /− mice. However, a Genotype × Drug interaction was observed for LBM ( p = 0.047) and FM ( p = 0.035) but not BMC ( p = .569). Whereas WT mice lost LBM and FM during CAF treatment, IL-6-deficient mice did not. Treatment-related decreases in levels of the anabolic hormone insulin-like growth factor-1 (IGF-1) may contribute to LBM and FM loss since CAF decreased IGF-1 levels in an IL-6-dependent manner. These findings implicate IL-6 and possibly IGF-1 in the regulation of body composition in breast cancer patients exposed to cytotoxic chemotherapy.

1985 ◽  
Vol 248 (2) ◽  
pp. R181-R189 ◽  
Author(s):  
J. L. Blank ◽  
C. Desjardins

The reproductive responses of two species of wild rodents, house mice and deer mice, were evaluated following a 30% reduction in food intake for 5 wk. These animal models were chosen as prototypes of other rodent species because each employs unique functional adjustments when confronted with reduced resources in their natural habitats. Modest inanition failed to alter pituitary-testicular function in house mice; neither spermatogenesis nor plasma concentrations of luteinizing hormone (LH) and testosterone were modified. In sharp distinction, deer mice exposed to restricted food intake showed significant reductions in plasma LH and testosterone and an accompanying loss in spermatogenesis. Reduced food intake also caused pronounced shifts in the temporal organization and amount of wheel-running activity in both animal models, albeit in a dichotomous fashion. House mice exhibited the same amount of wheel-running activity throughout inanition, but the diel periodicity of locomotor behavior was shifted from the dark to the light period. Deer mice, in comparison, significantly curtailed wheel-running activity during the dark hours but ran in precise phase relationship with the light-dark cycle. Taken together, our results establish that the male reproductive system and its supporting neuroendocrine and behavioral correlates can be disrupted by modest levels of food restriction in certain animal models.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 208-208
Author(s):  
Sravana K Chennupati ◽  
Faisal A Siddiqui ◽  
Tasha L. McDonald ◽  
Charles R. Thomas ◽  
Arthur Hung ◽  
...  

208 Background: Prostate cancer patients undergoing localized external beam radiation therapy (EBRT), experience significant fatigue during treatment, which can affect physical functioning and QOL. We hypothesize that cancer treatment related fatigue (CTRF) is the same as sickness behavior caused, in part, by increases in TNF-α. Our previous data demonstrate that pelvic EBRT induces systemic increases in TNF-α and a decline in voluntary wheel running activity (VWRA) , an objective measure of sickness in mice. A specific aim of this study was to determine the requirement of EBRT for TNF-α for the induction of sickness behavior. Methods: Daily VWRA was monitored in male WT (n=10) and TNF-α−/− (n=10) anesthetized mice undergoing pelvic EBRT at 4.6 Gy/fraction, 5 days per week for 15 fractions for a total dose of 69 Gy [4.6 X 15 = 69, not 70]. Control WT (n=10) and TNF-α−/− (n= 10) mice underwent anesthesia followed by sham EBRT. The effect of treatment on weight and food intake was also determined by calculating change in weight and daily food intake during treatment. A 2 x 2 repeated measure analysis of covariance ANCOVA was used to determine whether there was a significant interaction between treatment group (EBRT or Control) and genotype (WT or TNF-α−/−) on voluntary wheel running activity controlling for baseline differences in this variable. Similarly a 2 x 2 ANOVA was used to determine whether there was a drug x genotype interaction between change in body weight or food intake. Results: There was a significant effect of EBRT on VWRA (p< 0.001), food intake (p0.002), and weight (p<0.001). We did not however observe a significant interaction between EBRT and genotype in VWRA (p= 0.756), food intake (p=0.654), or weight (p= 0.450). Conclusions: Targeting TNF-α using specific cytokine blocking agents has been suggested as a potential strategy for preventing or managing EBRT related fatigue. Although our prior data support that localized EBRT to the pelvis may induce TNF-α and sickness behavior in mice, our latest data do not support a direct role for this cytokine in mediating these effects.


1993 ◽  
Vol 265 (3) ◽  
pp. R504-R511
Author(s):  
J. D. Glass ◽  
U. E. Hauser ◽  
J. L. Blank ◽  
M. Selim ◽  
M. A. Rea

In vivo brain microdialysis was used to characterize the daily pattern of extracellular excitatory amino acids (EAA; glutamate and aspartate), glutamine and 5-hydroxyindoleacetic acid (5-HIAA) in the region of the suprachiasmatic nucleus (SCN) in freely behaving male Syrian hamsters. Diurnal variations in the extracellular concentrations of EAA and 5-HIAA observed under 14:10-h light-dark (LD) photoperiod were confirmed by cosinor analysis. Peak levels occurred during the night, with the mean acrophasis for 5-HI-AA concentration preceding that for EAA by 1-2 h. Release of EAA was stimulated by K(+)-induced depolarization in a Ca(2+)-dependent manner and was not affected by tetrodotoxin. In the absence of light cues (constant dim red light, < 0.4 lx; DD) there was a significant time-of-day effect in peak glutamate concentration (occurring during subjective night), but the rhythmic pattern of 5-HIAA output was lost. There was no apparent direct temporal linkage between peaks in extracellular EAA or 5-HIAA and bouts of wheel-running activity under LD or DD. These results are evidence that 1) the daily release pattern of extracellular glutamate, but not 5-HIAA, is circadian in nature; and 2) this rhythm in glutamate is not based on Na+ channel-dependent action potentials. Finally, a discordance in the timing of peak nocturnal extracellular 5-HIAA and EAA concentrations was evident, possibly reflecting an interplay between serotonergic and EAA pathways in the SCN.


2007 ◽  
Vol 125 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Claudio Battaglini ◽  
Martim Bottaro ◽  
Carolyn Dennehy ◽  
Logan Rae ◽  
Edgar Shields ◽  
...  

CONTEXT AND OBJECTIVE: Changes in metabolism have been reported in the majority of patients undergoing cancer treatment, and these are usually characterized by progressive change in body composition. The effects of aerobic exercise programs to combat the cancer and cancer treatment-related side effects, which include the negative changes in body composition, have been extensively reported in the literature. However, few resistance exercise intervention studies have hypothesized that breast cancer patients might benefit from this type of exercise. The purpose of this study was to determine whether exercise protocols that emphasize resistance training would change body composition and strength in breast cancer patients undergoing treatment. DESIGN AND SETTING: Randomized controlled trial, at the Campus Recreation Center and Rocky Mountain Cancer Rehabilitation Institute of the University of Northern Colorado, and the North Colorado Medical Center. METHODS: Twenty inactive breast cancer patients were randomly assigned to a 21-week exercise group (n = 10) or a control group (n = 10). The exercise group trained at low to moderate intensity for 60 minutes on two days/week. The primary outcome measurements included body composition (skinfold method) and muscle strength (one repetition maximum). RESULTS: Significant differences in lean body mass, body fat and strength (p = 0.004, p = 0.004, p = 0.025, respectively) were observed between the groups at the end of the study. CONCLUSION: The results suggest that exercise emphasizing resistance training promotes positive changes in body composition and strength in breast cancer patients undergoing treatment.


The Breast ◽  
2015 ◽  
Vol 24 ◽  
pp. S106-S107
Author(s):  
T. Iwase ◽  
T. Sangai ◽  
E. Ishigami ◽  
J. Sakakibara ◽  
K. Fujisaki ◽  
...  

2009 ◽  
Vol 39 (1) ◽  
pp. 47-55 ◽  
Author(s):  
He S. Yang ◽  
Martha H. Vitaterna ◽  
Aaron D. Laposky ◽  
Kazuhiro Shimomura ◽  
Fred W. Turek

There is considerable evidence for a genetic basis underlying individual differences in spontaneous physical activity in humans and animals. Previous publications indicate that the physical activity level and pattern vary among inbred strains of mice and identified a genomic region on chromosome 13 as quantitative trait loci (QTL) for physical activity. To confirm and further characterize the role of chromosome 13 in regulating daily physical activity level and pattern, we conducted a comprehensive phenotypic study in the chromosome 13 substitution strain (CSS-13) in which the individual chromosome 13 from the A/J strain was substituted into an otherwise complete C57BL/6J (B6) genome. The B6 and A/J parental strains exhibited pronounced differences in daily physical activity, sleep-wake structure, circadian period and body weight. Here we report that a single A/J chromosome 13 in the context of a B6 genetic background conferred a profound reduction in both total cage activity and wheel-running activity under a 14:10-h light-dark cycle, as well as in constant darkness, compared with B6 controls. Additionally, CSS-13 mice differed from B6 controls in the diurnal distribution of activity and the day-to-day variability in activity onset. We further performed a linkage analysis and mapped a significant QTL on chromosome 13 regulating the daily wheel running activity level in mice. Taken together, our findings indicate a QTL on chromosome 13 with dramatic and specific effects on daily voluntary physical activity, but not on circadian period, sleep, or other aspects of activity that are different between B6 and A/J strains.


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