Body weight loss in beef cows: II. Increased antioxidant messenger ribonucleic acid levels in skeletal muscle but not erythrocyte antioxidant activity

Abstract Background Cancer cachexia is a catabolic condition characterized by skeletal muscle wasting, consequent to tumor burden, which negatively impacts tolerance to cancer therapies and contributes to increased mortality. Partly because of the limited knowledge of the underlying mechanisms of cancer cachexia derived from human studies, however, the ability to therapeutically intervene remains elusive. The purpose of the current study was therefore to better define the phenotype of skeletal muscle obtained from patients with pancreatic ductal adenocarcinoma (PDAC), which has one of the highest rates of cachexia. Methods Morphological analyses were performed on rectus abdominis muscle biopsies obtained from resectable PDAC patients undergoing tumor resection surgery (N = 20) and from weight-stable non-cancer control subjects undergoing benign abdominal surgery (N = 16). PDAC patients with a body weight loss of greater than 5% during the previous 6 months were considered cachectic (N = 15). Statistical tests were two sided. Results Skeletal muscle from cachectic PDAC patients had increased collagen content compared with non-cancer control subjects (1.43% vs 9.66%, P = .0004, Dunn test). Across all PDAC patients, collagen content positively correlated with body weight loss (P = .0016, r = 0.672), was increased in patients with lymph node metastasis (P = .007, Mann-Whitney U test), and was associated with survival on univariate (HR = 1.08, 95% confidence interval [CI] = 1.02 to 1.04, P = .008) and multivariable analyses (HR = 1.08, 95% CI = 1.00 to 1.17, P = .038). Cachectic PDAC patients also displayed increased lipid deposition (2.63% vs 5.72%, P = .042), infiltration of CD68+ macrophages (63.6 cells/mm2 vs 233.8 cells/mm2, P = .0238), calcium deposition (0.21% vs 2.51%, P = .030), and evidence of deficient cellular quality control mechanisms (Mann-Whitney U test). Transcriptional profiling of all patients supported these findings by identifying gene clusters related to wounding, inflammation, and cellular response to TGF-β upregulated in cachectic PDAC patients compared with non-cancer control subjects. Conclusions To our knowledge, this work is the first to demonstrate increased collagen content in cachectic PDAC patients that is associated with poor survival.

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OP032 INCREASED LYSOSOMAL ACTIVITY IN SKELETAL MUSCLE IS ASSOCIATED WITH BODY WEIGHT LOSS IN PATIENTS WITH CANCER

Clinical Nutrition Supplements ◽

10.1016/s1744-1161(12)70033-9 ◽

2012 ◽

Vol 7 (1) ◽

pp. 14

Author(s):

N. Tardif ◽

M. Klaude ◽

L. Lundell ◽

A. Thorell ◽

O. Rooyackers

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Body Weight Loss ◽

Lysosomal Activity ◽

Patients With Cancer

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Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice

FEBS Letters ◽

10.1016/j.febslet.2014.03.051 ◽

2014 ◽

Vol 588 (10) ◽

pp. 1935-1941 ◽

Cited By ~ 44

Author(s):

Taro Usui ◽

Kazuo Kajita ◽

Toshiko Kajita ◽

Ichiro Mori ◽

Takayuki Hanamoto ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Mitochondrial Biogenesis ◽

Body Weight Loss ◽

Male Mice

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The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

10.21203/rs.3.rs-40261/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Brandon VanderVeen ◽

Alexander T. Sougiannis ◽

Kandy T. Velazquez ◽

James A. Carson ◽

Daping Fan ◽

...

Keyword(s):

Skeletal Muscle ◽

Bone Marrow ◽

Weight Loss ◽

Body Weight ◽

Immune Cells ◽

Immune Cell ◽

Body Weight Loss ◽

Acute Effects ◽

First Choice ◽

The Impact

Abstract Background: 5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g. colon, breast, head & neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical setting and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through both the removal of damaged or old materials and coordinate repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation toimpact resident and infiltrating skeletal muscle immune cells had not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Methods: Male C57BL/6 mice were given a physiologically translatable dose (35mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Results: Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (>5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophageswere reduced with 5FU treatment while total M2-like CD206+CD11c-macrophageswere not changed with 5FU. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes.Conclusions: Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in associated with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest.Together our results highlight that skeletal muscle is sensitive to the cytotoxic effects of 5FU which disrupts both circulating and skeletal muscle immune cells.

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Ghrelin improves body weight loss and skeletal muscle catabolism associated with angiotensin II-induced cachexia in mice

Regulatory Peptides ◽

10.1016/j.regpep.2012.06.003 ◽

2012 ◽

Vol 178 (1-3) ◽

pp. 21-28 ◽

Cited By ~ 26

Author(s):

Masako Sugiyama ◽

Akira Yamaki ◽

Mayumi Furuya ◽

Norio Inomata ◽

Yoshiharu Minamitake ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Angiotensin Ii ◽

Body Weight Loss ◽

Muscle Catabolism

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Differential effects of rapid or slow body weight loss on muscle weight and protein degradation pathways in rat skeletal muscle

Journal of the International Society of Sports Nutrition ◽

10.1186/1550-2783-12-s1-p58 ◽

2015 ◽

Vol 12 (S1) ◽

Author(s):

Yudai Nonaka ◽

Shin Terada

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Body Weight ◽

Protein Degradation ◽

Body Weight Loss ◽

Degradation Pathways ◽

Rat Skeletal Muscle ◽

Muscle Weight ◽

Differential Effects

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The survival feeding of pregnant and lactating beef cows on all-sorghum grain rations: the effects of two levels of grain and early weaning of the calves

The Journal of Agricultural Science ◽

10.1017/s0021859600025120 ◽

1970 ◽

Vol 75 (3) ◽

pp. 479-484 ◽

Cited By ~ 3

Author(s):

J. G. Morris

Keyword(s):

Weight Loss ◽

Body Weight ◽

Birth Weight ◽

Body Weight Loss ◽

Beef Cows ◽

The Body ◽

Clinical Effects ◽

Early Weaning ◽

Sorghum Grain

SUMMARYForty-six cows in store condition (mean ± S.E. body weight of 366 ± 8 kg) were fed individually either 3 or 4 kg of coarsely rolled sorghum grain/head/day for the last 100 days of pregnancy and the subsequent 70 days after parturition. Eleven of the cows on each level of feeding had their calves weaned at 3 days of age.For the last 100 days of pregnancy, 3 kg of grain/head/day was an adequate ration for survival, but cows fed this ration lost a mean of 34 kg of body weight over this period compared to 8 kg by cows fed 4 kg of grain/head/day. Only 78% of the cows fed 3 kg grain/day survived to 70 days after parturition, whereas all cows fed 4 kg/day survived. There was a 44% incidence of retained placentae and metritis in cows fed 3 kg grain/day whereas those fed 4 kg/day had only an 18% incidence. Weaning of the calves at 3 days of age reduced the body weight loss of the cows by a mean of 40 kg over the first 70 days of lactation, but the effect was less for cows fed 3 kg grain (27 kg) than for those fed 4 kg grain (53 kg).Birth weight of the calves was not affected by the level of grain fed to the cows, but calves weaned and given 3 kg of milk/day plus a 50/50 creep of lucerne chaff and sorghum grain grew faster than calves not weaned and given only a sorghum grain creep.The omission of a source of calcium in the grain ration resulted in no apparent adverse clinical effects in the cows. The Na:K ratio of the saliva indicated that nine of the cows had been depleted of Na.

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The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

Frontiers in Physiology ◽

10.3389/fphys.2020.593468 ◽

2020 ◽

Vol 11 ◽

Author(s):

Brandon N. VanderVeen ◽

Alexander T. Sougiannis ◽

Kandy T. Velazquez ◽

James A. Carson ◽

Daping Fan ◽

...

Keyword(s):

Skeletal Muscle ◽

Bone Marrow ◽

Weight Loss ◽

Body Weight ◽

Immune Cells ◽

Immune Cell ◽

Body Weight Loss ◽

Acute Effects ◽

First Choice ◽

The Impact

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through removal of damaged or old materials as well as coordinate skeletal muscle repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation to impact resident and infiltrating skeletal muscle immune cells has not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Male C57BL/6 mice were given a physiologically translatable dose (35 mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (>5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophages were reduced with 5FU treatment while total M2-like CD206+CD11c- macrophages were unchanged. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes. Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in association with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest. Together our results highlight that skeletal muscle is sensitive to 5FU’s off-target effects which disrupts both circulating and skeletal muscle immune cells.

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