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Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.

ABSTRACT: Background:Cancer survivors experience on average a 20% reduction in peak exercise capacity (VO2 peak) post-cancer treatment. Intermuscular fat (IMF) is a strong predictor of reduced exercise capacity in heart failure (HF) patients; however it is unknown whether increased IMF is related to reduced VO2 peak in cancer survivors. Methods and results:Twenty eight individuals: 14 cancer survivors >?12-months post-cancer treatment and 14 individuals without cancer were matched on age, gender, and body mass index (BMI). Participants underwent magnetic resonance imaging (MRI) assessments of IMF within the paraspinal muscles, VO2 peak and exercise-associated measures of left ventricular ejection fraction (LVEF). Blinded analyses were performed. Associations between the ratio of IMF to skeletal muscle (SM) were estimated using Pearson's partial correlation coefficients. Individuals with cancer and non-cancer comparators were of similar age (54?±?17 versus 54?±?15?years; p?=?1.0), gender (5 men and 9 women, both groups), and BMI (27?±?4 versus 26?±?4; p?=?0.57). Peak VO2 was 22% lower in cancer survivors versus non-cancer comparators (26.9 vs 34.3?ml/kg/min; p?=?0.005), and was correlated with IMF:SM in both cancer survivors and non-cancer individuals after accounting for exercise-associated LVEF, resting LVEF, BMI, other body fat depots, and cardiovascular disease (CVD) co-morbidities (p?

SUBMITTER: Reding KW

PROVIDER: S-EPMC7048042 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.

Reding Kerryn W KW Brubaker Peter P D'Agostino Ralph R Kitzman Dalane W DW Nicklas Barbara B Langford Dale D Grodesky Michael M Hundley W Gregory WG

Cardio-oncology (London, England) 20190503

<h4>Background</h4>Cancer survivors experience on average a 20% reduction in peak exercise capacity (VO<sub>2 peak</sub>) post-cancer treatment. Intermuscular fat (IMF) is a strong predictor of reduced exercise capacity in heart failure (HF) patients; however it is unknown whether increased IMF is related to reduced VO<sub>2 peak</sub> in cancer survivors.<h4>Methods and results</h4>Twenty eight individuals: 14 cancer survivors > 12-months post-cancer treatment and 14 individuals without cancer ...[more]

PMID: 32154010

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Project description:BackgroundThe body composition of patients with rectal cancer potentially affects postoperative outcomes. This study explored the correlations between skeletal muscle and adipose tissue quantified by computed tomography (CT) with postoperative complications and long-term prognosis in patients with rectal cancer after surgical resection.MethodsThis retrospective cohort study included patients with rectal cancer who underwent surgical resection at the Wuhan Union Hospital between 2014 and 2018. CT images within 3 months prior to the surgery were used to quantify the indices of skeletal muscle and adipose tissue at the levels of the third lumbar vertebra (L3) and umbilicus. Optimal cut-off values for each index were defined separately for males and females. Associations between body composition and postoperative complications, overall survival (OS), and disease-free survival (DFS) were evaluated using logistic and Cox proportional hazards models.ResultsWe included 415 patients (240 males and 175 females; mean age: 57.8 ± 10.5 years). At the L3 level, a high skeletal muscle density (SMD; hazard ratio [HR]: 0.357, 95% confidence interval [CI]: 0.191-0.665, P = 0.001; HR: 0.571, 95% CI: 0.329-0.993, P = 0.047) and a high skeletal muscle index (SMI; HR: 0.435, 95% CI 0.254-0.747, P = 0.003; HR: 0.568, 95% CI: 0.359-0.897, P = 0.015) were independent prognostic factors for better OS and DFS. At the umbilical level, a large intermuscular fat area (IMFA; HR: 1.904, 95% CI: 1.068-3.395, P = 0.029; HR: 2.064, 95% CI: 1.299-3.280, P = 0.002) was an independent predictive factor for worse OS and DFS, and a high SMI (HR: 0.261, 95% CI: 0.132-0.517, P < 0.001; HR: 0.595, 95% CI: 0.387-0.913, P = 0.018) was an independent prognostic factor for better OS and DFS. The models combining body composition and clinical indicators had good predictive abilities for OS. The receiver operating characteristic areas under the curve were 0.848 and 0.860 at the L3 and umbilical levels, respectively (both P < 0.05).ConclusionsNo correlations existed between CT-quantified body composition parameters and postoperative complications. However, a high SMD and high SMI were significantly associated with longer OS and DFS at the L3 level, whereas a large IMFA and low SMI were associated with worse OS and DFS at the umbilical level. Combining CT-quantified body composition and clinical indicators could help physicians predict the prognosis of patients with rectal cancer after surgery.

Project description:Background/objectivesLimited numbers of studies demonstrated obesity-induced macrophage infiltration in skeletal muscle (SM), but dynamics of immune cell accumulation and contribution of T cells to SM insulin resistance are understudied.Subjects/methodsT cells and macrophage markers were examined in SM of obese humans by reverse transcription-PCR (RT-PCR). Mice were fed high-fat diet (HFD) for 2-24 weeks, and time course of macrophage and T-cell accumulation was assessed by flow cytometry and quantitative RT-PCR. Extramyocellular adipose tissue (EMAT) was quantified by high-resolution micro-computed tomography (CT), and correlation to T-cell number in SM was examined. CD11a-/- mice and C57BL/6 mice were treated with CD11a-neutralizing antibody to determine the role of CD11a in T-cell accumulation in SM. To investigate the involvement of Janus kinase/signal transducer and activator of transcription (JAK/STAT), the major pathway for T helper I (TH1) cytokine interferon-γ, in SM and adipose tissue inflammation and insulin resistance, mice were treated with a JAK1/JAK2 inhibitor, baricitinib.ResultsMacrophage and T-cell markers were upregulated in SM of obese compared with lean humans. SM of obese mice had higher expression of inflammatory cytokines, with macrophages increasing by 2 weeks on HFD and T cells increasing by 8 weeks. The immune cells were localized in EMAT. Micro-CT revealed that EMAT expansion in obese mice correlated with T-cell infiltration and insulin resistance. Deficiency or neutralization of CD11a reduced T-cell accumulation in SM of obese mice. T cells polarized into a proinflammatory TH1 phenotype, with increased STAT1 phosphorylation in SM of obese mice. In vivo inhibition of JAK/STAT pathway with baricitinib reduced T-cell numbers and activation markers in SM and adipose tissue and improved insulin resistance in obese mice.ConclusionsObesity-induced expansion of EMAT in SM was associated with accumulation and proinflammatory polarization of T cells, which may regulate SM metabolic functions through paracrine mechanisms. Obesity-associated SM 'adiposopathy' may thus have an important role in the development of insulin resistance and inflammation.

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Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.

Publications

Increased skeletal intermuscular fat is associated with reduced exercise capacity in cancer survivors: a cross-sectional study.

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