Dataset Information

Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia.

ABSTRACT:

Scope

Cancer cachexia is characterized by the loss of skeletal muscle resulting in functional impairment, reduced quality of life and mortality. Naringenin, a flavonoid found in citrus fruits, improves insulin sensitivity and reduces inflammation and tumor growth in preclinical models. Therefore, the study hypothesizes that dietary supplementation of naringenin will improve insulin sensitivity, decrease inflammation, slow body weight loss, and delay tumor growth in a mouse model of cancer cachexia.

Methods and results

Mice are fed 2 wt% dietary naringenin before and during initiation of cancer cachexia using inoculated adenocarcinoma-26 cells (C-26). Food intake, body weight, body composition, muscle function, insulin tolerance, and inflammatory status are assessed. Although naringenin-fed tumor-bearing mice exhibit reductions in body weight and food intake earlier than control diet-fed tumor-bearing mice, dietary naringenin is protective against loss of muscle strength, and attenuates the onset of insulin resistance and markers of inflammation.

Conclusions

Dietary supplementation of naringenin improves multiple aspects of metabolic disturbance and inflammation during cancer cachexia progression in [C-26 tumor-bearing] mice. However, the acceleration of anorexia and weight loss is also observed. These findings emphasize the link between inflammation and insulin resistance as a basis for understanding their roles in the pathogenesis of cancer cachexia.

SUBMITTER: Snoke DB

PROVIDER: S-EPMC8612985 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia.

Snoke Deena B DB Nishikawa Yuko Y Cole Rachel M RM Ni Ai A Angelotti Austin A Vodovotz Yael Y Belury Martha A MA

Molecular nutrition & food research 20210927 22

<h4>Scope</h4>Cancer cachexia is characterized by the loss of skeletal muscle resulting in functional impairment, reduced quality of life and mortality. Naringenin, a flavonoid found in citrus fruits, improves insulin sensitivity and reduces inflammation and tumor growth in preclinical models. Therefore, the study hypothesizes that dietary supplementation of naringenin will improve insulin sensitivity, decrease inflammation, slow body weight loss, and delay tumor growth in a mouse model of cance ...[more]

PMID: 34499400

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Project description:BackgroundThe cachexia index is a useful predictor for cancer cachexia and prognostic assessment. However, its use is limited because of high testing costs and complicated testing procedures. Thus, in this study, we aimed to develop a hand grip strength (HGS)-based cancer cachexia index (H-CXI) as a potential predictor of cancer cachexia and prognosis in patients with cancer.MethodsHere, 14 682 patients with cancer were studied, including the discovery (6592), internal validation (2820) and external validation (5270) cohorts. The H-CXI was calculated as [HGS (kg)/height (m)2 × serum albumin (g/L)]/neutrophil-to-lymphocyte ratio. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). Logistic regression analysis was used to assess the association of the H-CXI with short-term outcomes and cancer cachexia.ResultsThere was a significant non-linear relationship between the H-CXI and OS in all cohorts. Patients with a low H-CXI had significantly lower OS than those with a high H-CXI in the discovery cohort (6-year survival percentage: 55.72% vs. 76.70%, log-rank P < 0.001), internal validation cohort (6-year survival percentage: 55.81% vs. 76.70%, log-rank P < 0.001), external validation cohort (6-year survival percentage: 56.05% vs. 75.48%, log-rank P < 0.001) and total cohort (6-year survival percentage: 55.86% vs. 76.27%, log-rank P < 0.001). Notably, the prognostic stratification effect of the H-CXI in patients with advanced-stage disease was more significant than that in patients with early-stage disease. The multivariate Cox proportional risk regression model confirmed that a low H-CXI negatively affected the prognosis of patients with cancer in the discovery cohort [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.71-0.80, P < 0.001], internal validation cohort (HR 0.79, 95 %CI 0.72-0.86, P < 0.001), external validation cohort (HR 0.84, 95% CI 0.79-0.89, P < 0.001) and total cohort (HR 0.80, 95% CI 0.77-0.83, P < 0.001). Multivariate logistic regression models showed that a low H-CXI was an independent risk factor predicting adverse short-term outcomes and cancer cachexia in patients with cancer.ConclusionsThe simple and practical H-CXI is a promising predictor for cancer cachexia and prognosis in patients with cancer.

Project description:BackgroundsHand grip strength (HGS) is one of diagnose criteria factors of sarcopenia and is associated with the survival of patients with cancer. However, few studies have addressed the association of HGS and 1 year mortality of patients with cancer cachexia.MethodsThis cohort study included 8466 patients with malignant solid tumour from 40 clinical centres throughout China. Cachexia was diagnosed using the 2011 International cancer cachexia consensus. The hazard ratio (HR) of all cancer cachexia mortality was calculated using Cox proportional hazard regression models. Kaplan-Meier curves were generated to evaluate the association between HGS and the 1 year mortality of patients with cancer cachexia. The interaction analysis was used to explore the combined effect of low HGS and other factors on the overall survival of patients with cancer cachexia.ResultsAmong all participants, 1434 (16.9%) patients with cancer were diagnosed with cachexia according to the 2011 International cancer cachexia consensus with a mean (SD) age of 57.75 (12.97) years, among which there were 871 (60.7%) male patients. The HGS optimal cut-off points of male and female patients were 19.87 and 14.3 kg, respectively. Patients with cancer cachexia had lower HGS than those patients without cachexia (P < 0.05). In the multivariable Cox analysis, low HGS was an independent risk factor of cachexia [HR: 1.491, 95% confidence interval (CI): 1.257-1.769] after adjusting other factors. In addition, all of cancer cachexia patients with lower HGS had unfavourable 1 year survival (P < 0.001). In a subset analysis, low HGS was an independent prognosis factor of male patients with cancer cachexia (HR: 1.623, 95% CI: 1.308-2.014, P < 0.001), but not in female patients (HR: 1.947, 95% CI: 0.956-3.963, P = 0.0662), and low HGS was associated with poor 1 year survival of digestive system, respiratory system, and other cancer cachexia patients (all P < 0.05). Low HGS has combined effects with high neutrophil-to-lymphocyte ratio or low albumin on unfavourable overall survival of patients with cancer cachexia.ConclusionsLow HGS was associated with poor 1 year survival of patients with cancer cachexia.

Project description:BackgroundAlthough body mass index (BMI) and grip strength (GS) are both predictors of disability, their joint effect on predicting incident disability remains uncertain. We examined whether the effect of BMI on incident disability can be modulated by GS in community-dwelling older people in Japan.MethodsA total of 1486 community-dwellers in Japan (731 men and 755 women, aged 65-82 years) who participated in the 2nd to 7th waves of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project, were followed up to 20 years. Twelve subgroups were created according to the intersections of GS (sex-specific tertiles: low, intermediate, and high) and BMI (underweight 1, <18.5; underweight 2, 18.5-<21.5; normal, 21.5-<25.0; and overweight/obese, ≥25.0 kg/m2 ). Incident disability was defined as requiring care need level 1 or higher, as per the long-term care insurance system in Japan. The hazard ratios (HR) and corresponding 95% confidence intervals (CI) of incident disability (the 'high GS-normal BMI' subgroup was used as the reference) were calculated using a multivariable-adjusted Cox proportional hazards model. The model was adjusted for baseline characteristics on sex, participation wave, smoking, depressive symptoms, total physical activity, disease history, education level, residential status, and energy intake.ResultsCompared with that for participants in the 'high GS-normal BMI' group, the risk of incident disability was higher for participants in the 'low GS-normal BMI', 'low GS-overweight/obese', 'intermediate GS-underweight 1' and 'intermediate GS-overweight/obese' groups. The multivariable-adjusted HR (95% CI) were 1.72 (1.27-2.32, P value<0.001), 1.81 (1.27-2.58, P value = 0.001), 2.42 (1.35-4.32, P value = 0.003) and 1.53 (1.06-2.20, P value = 0.023), respectively. The results did not change substantially when participants with disability occurring within 1 and 2 years of follow-up were excluded, or when the competing events were death without incident disability or dementia.ConclusionsThe joint effect of BMI and GS was more pronounced in those of normal weight or overweight/obese status and low GS, along with underweight or overweight/obese status and intermediate GS in predicting disability. The lack of observed joint effect for those underweight with low GS was likely due to insufficient sample size. GS consideration is necessary for weight management in older adults, and interventions for individuals who are underweight or overweight/obese with adequate GS need not be prioritized for disability prevention.

Dataset Information

Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia.

Scope

Methods and results

Conclusions

Publications

Dietary Naringenin Preserves Insulin Sensitivity and Grip Strength and Attenuates Inflammation but Accelerates Weight Loss in a Mouse Model of Cancer Cachexia.

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