Body weight loss in beef cows: I. The effect of increased β-oxidation on messenger ribonucleic acid levels of uncoupling proteins two and three and peroxisome proliferator-activated receptor in skeletal muscle

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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Adaptor Protein SH2-B Linking Receptor-Tyrosine Kinase and Akt Promotes Adipocyte Differentiation by Regulating Peroxisome Proliferator-Activated Receptor γ Messenger Ribonucleic Acid Levels

Molecular Endocrinology ◽

10.1210/me.2006-0413 ◽

2007 ◽

Vol 21 (5) ◽

pp. 1120-1131 ◽

Cited By ~ 21

Author(s):

Daigo Yoshiga ◽

Naoichi Sato ◽

Takehiro Torisu ◽

Hiroyuki Mori ◽

Ryoko Yoshida ◽

...

Keyword(s):

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Ribonucleic Acid ◽

Adipocyte Differentiation ◽

Adaptor Protein ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Messenger Ribonucleic Acid

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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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