Dataset Information

Formation of colorectal liver metastases induces musculoskeletal and metabolic abnormalities consistent with exacerbated cachexia.

ABSTRACT: Advanced colorectal cancer (CRC) is often accompanied by development of liver metastases (LMs) and skeletal muscle wasting (i.e., cachexia). Despite plaguing the majority of CRC patients, cachexia remains unresolved. By using mice injected with Colon-26 mouse tumors, either subcutaneously (s.c.; C26) or intrasplenically to mimic hepatic dissemination of cancer cells (mC26), here we aimed to further characterize functional, molecular, and metabolic effects on skeletal muscle and examine whether LMs exacerbate CRC-induced cachexia. C26-derived LMs were associated with progressive loss of body weight, as well as with significant reductions in skeletal muscle size and strength, in line with reduced phosphorylation of markers of protein anabolism and enhanced protein catabolism. mC26 hosts showed prevalence of fibers with glycolytic metabolism and enhanced lipid accumulation, consistent with abnormalities of mitochondrial homeostasis and energy metabolism. In a comparison with mice bearing s.c. C26, cachexia appeared exacerbated in the mC26 hosts, as also supported by differentially expressed pathways within skeletal muscle. Overall, our model recapitulates the cachectic phenotype of metastatic CRC and reveals that formation of LMs resulting from CRC exacerbate cancer-induced skeletal muscle wasting by promoting differential gene expression signatures.

SUBMITTER: Huot JR

PROVIDER: S-EPMC7253026 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Formation of colorectal liver metastases induces musculoskeletal and metabolic abnormalities consistent with exacerbated cachexia.

Huot Joshua R JR Novinger Leah J LJ Pin Fabrizio F Narasimhan Ashok A Zimmers Teresa A TA O'Connell Thomas M TM Bonetto Andrea A

JCI insight 20200507 9

Advanced colorectal cancer (CRC) is often accompanied by development of liver metastases (LMs) and skeletal muscle wasting (i.e., cachexia). Despite plaguing the majority of CRC patients, cachexia remains unresolved. By using mice injected with Colon-26 mouse tumors, either subcutaneously (s.c.; C26) or intrasplenically to mimic hepatic dissemination of cancer cells (mC26), here we aimed to further characterize functional, molecular, and metabolic effects on skeletal muscle and examine whether L ...[more]

PMID: 32298240

Similar Datasets

Project description:Background:Poor sleep is a potential risk factor for metabolic syndrome (MetS), and its relationship with MetS may vary by race/ethnicity and menopausal status among women. Methods:We used Sister Study enrollment data from 2003 to 2009 to investigate the cross-sectional associations between multiple subjective sleep characteristics and having???3 prevalent metabolic abnormalities consistent with MetS among white, black, and Hispanic/Latina women. Self-reported sleep characteristics included average sleep duration (short [<?7 h] vs. recommended [7-9 h]), sleep debt (??2-h difference between shortest and longest sleep duration, napping???3 times/week, and insomnia symptoms (difficulty falling or staying asleep). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) to compare MetS prevalence between women with poor sleep (e.g., short sleep, sleep debt, frequent napping, or insomnia symptoms [all yes vs. no]) and non-poor sleep within menopausal status categories (premenopausal or postmenopausal). We adjusted for sociodemographic characteristics, mental health, and health behaviors. Results:Among 38,007 eligible women (13,988 premenopausal, 24,019 postmenopausal), mean age was 55?±?8.8 years, racial/ethnic composition was 86.63% white, 8.53% black, and 4.84% Hispanic/Latina, and 12% had MetS. Associations between certain poor sleep characteristics [i.e., short sleep (PRpremenopausal?=?1.23 [95% CI 1.06-1.42], PRpostmenopausal?=?1.09 [1.02-1.16], pshort sleep*menopause?=?0.0070) and insomnia symptoms (PRpremenopausal?=?1.21 [1.05-1.41], PRpostmenopausal?=?1.11 [1.05-1.18], pinsomnia symptoms*menopause?=?0.035)] and prevalent MetS were stronger among premenopausal compared to postmenopausal women, but did not vary by race/ethnicity. Associations between concurrent short sleep/insomnia symptoms and MetS were stronger among white and Hispanic/Latina postmenopausal women compared to their black counterparts. Menopausal status and race/ethnicity did not modify positive associations for other poor sleep characteristics. Conclusions:Poor sleep was positively associated with MetS prevalence. Associations between individual poor sleep characteristics (i.e., short sleep, insomnia symptoms) were stronger among premenopausal compared to postmenopausal women but did not vary by race/ethnicity.

Dataset Information

Formation of colorectal liver metastases induces musculoskeletal and metabolic abnormalities consistent with exacerbated cachexia.

Publications

Formation of colorectal liver metastases induces musculoskeletal and metabolic abnormalities consistent with exacerbated cachexia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets