The Clinical Value of Nutritional Care before and during Active Cancer Treatment.

Malnutrition and muscle wasting are frequently reported in cancer patients, either linked to the tumor itself or caused by oncologic therapies. Understanding the value of nutritional care during cancer treatment remains crucial. In fact, cancer-associated sarcopenia plays a key role in determining higher rates of morbidity, mortality, treatment-induced toxicities, prolonged hospitalizations and reduced adherence to anticancer treatment, worsening quality of life and survival. Planning baseline screening to intercept nutritional troubles earlier, organizing timely reassessments, and providing adequate counselling and dietary support, healthcare professional may positively interfere with this process and improve patients' overall outcomes during the whole disease course. Several screening tools have been proposed for this purpose. Nutritional Risk Screening (NRS), Mini Nutritional Assessment (MNA), Patient Generated Subjective Global Assessment (PG-SGA) are the most common studied. Interestingly, second-level tools including skeletal muscle index (SMI) and bioelectric impedance analysis (BIA) provide a more precise assessment of body composition, even if they are more complex. However, nutritional assessment is not currently used in clinical practice and procedures must be standardized in order to improve the efficacy of standard chemotherapy, targeted agents or even checkpoint inhibitors that is potentially linked with the patients' nutritional status. In the present review, we will discuss about malnutrition and the importance of an early nutritional assessment during chemotherapy and treatment with novel checkpoint inhibitors, in order to prevent treatment-induced toxicities and to improve survival outcomes.

The Association of Targeted Gut Microbiota with Body Composition in Type 2 Diabetes Mellitus.

The association between body composition and gut microbiota in type 2 diabetes mellitus (DM) remains unknown. To elucidate the correlation of body composition and gut microbiota, we conducted a clinical study to enroll 179 patients with type 2 DM. Body composition of lean tissue index (LTI) and fat tissue index was measured by Body Composition Monitor. Eight pairs of 16S rRNA gene primers specific to Firmicutes, Bacteroidetes, the Clostridium leptum group, Bacteroides, Bifidobacterium, Akkermansia muciniphila, Escherichia coli, and Faecalibacterium prausnitzii were used to measure their abundance by quantitative polymerase chain reaction. The results showed that type 2 DM with higher abundance of phylum Firmicutes and a higher ratio of phyla Firmicutes to Bacteroidetes (phyla F/B ratio) had higher LTI. This significant correlation between phyla F/B ratio and LTI was especially evident in type 2 DM with high body mass index, and independent of glycemic control or dipeptidyl peptidase-4 inhibitor usage. In conclusion, our study demonstrated the positive association of LTI with the abundance of phylum Firmicutes and the phyla F/B ratio in type 2 DM.

Peripheral Lymphocytes, Obesity, and Metabolic Syndrome in Young Adults: An Immunometabolism Study.

BACKGROUND: Obesity is characterized by a low-intensity chronic inflammatory process in which immune system cells interact in a complex network, which affects systemic metabolic processes. This raises interest in analyzing possible changes in the proportions of immune system cells in individuals with obesity with and without metabolic syndrome (MS), in relation to their body composition. METHODS: Circulating cells were analyzed with flow cytometry in young adults: monocytes, granulocytes, lymphocytes (T, B, and natural killer [NK]), TCD4+CD62-, TCD8+CD28-, and naive and memory cells of TCD3+ and TCD4+. Body composition was obtained by bioelectrical impedance analysis and dual-energy X-ray absorptiometry, and metabolic parameters. RESULTS: A total of 169 persons were evaluated: 20% presented normal body mass index (BMI); 49% was overweight, and 31% had obesity; 28% had MS. It was observed that with an increase in BMI and visceral adipose tissue increase (VATI), body composition and biochemical variables were negatively altered. With regard to cell subpopulations, total lymphocytes increased and granulocytes and NK lymphocytes decreased in patients with MS and VATI. Memory cells increased with BMI and VATI. In individuals with MS, monocytes, and NK lymphocytes comprised a negative association with VAT, fat mass, and skeletal muscle mass (SMM). In individuals with MS and VATI, a negative correlation was observed between monocytes and SMM. CONCLUSIONS: Significant changes were detected in the subpopulations of lymphocytes, suggesting that weight gain, SMM, and VAT accumulation gave rise to immunological changes at the peripheral level, and the presence of increased memory cells could be related to low-intensity chronic inflammation.

Role of Anti-Inflammatory Cytokines on Muscle Mass and Performance Changes in Elderly Men and Women.

OBJECTIVES: Investigate the presence of a correlation between systemic inflammatory profile of community-dwelling individuals and the loss of muscular mass and performance in old age over a 4.5y follow-up, focusing on the role of anti-inflammatory cytokines in muscular changes in elderly. DESIGN: Longitudinal clinical study. SETTING: Subjects were randomly selected from lists of 11 general practitioners in the city of Verona, Italy. PARTICIPANTS: The study included 120 subjects, 92 women and 28 men aged 72.27±2.06 years and with BMI of 26.52±4.07 kg/m2 at baseline. MEASUREMENTS: Six minutes walking test (6MWT), appendicular and leg fat free mass (FFM) as measured with Dual Energy X-ray absorptiometry, were obtained at baseline and after 4.5 years (4.5y) of mean follow-up. Height, weight, body mass index (BMI), and circulating levels of TNFα, IL-4, IL-10, and IL-13 were evaluated at baseline. RESULTS: A significant reduction of appendicular FFM, leg FFM and 6MWT performance (all p<0.001) was observed after 4.5 y follow-up. In a stepwise regression model, considering appendicular FFM decline as dependent variable, lnIL-4, BMI, baseline appendicular FFM, lnTNFα and lnIL-13 were significant predictors of appendicular FFM decline explaining 30.8% of the variance. While building a stepwise multiple regression considering leg FFM as a dependent variable, lnIL-4, BMI and leg FFM were significant predictors of leg FFM decline and explained 27.4% of variance. When considering 6MWT decline as a dependent variable, baseline 6MWT, lnIL-13 and lnTNFα were significant predictors of 6MWT decline to explain 22.9% of variance. CONCLUSIONS: Our study suggest that higher serum levels of anti-inflammatory markers, and in particular IL-4 and IL-13, may play a protective role on FFM and performance maintenance in elderly subjects.

Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.

Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through ß3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1-/- and interleukin-4 receptor-α double-negative (Il4ra-/-) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

Body composition of the host influences dendritic cell phenotype in patients treated for colorectal cancer.

Dendritic cells (DCs) are antigen-presenting cells that can acquire tumour antigens and initiate cytotoxic T cell reactions. Obesity has been proposed as a cause for tumours escaping immune surveillance, but few studies investigate the impact of other body composition parameters. We examined the relationship of DC phenotype with computer tomography (CT)-defined parameters in patients with colorectal cancer (CRC). DCs were identified within peripheral blood mononuclear cells by flow cytometry as HLA-DR positive and negative for markers of other cell lineages in 21 patients. Analysis of CT scans was used to calculate lumbar skeletal muscle index (LSMI) and mean muscle attenuation (MA). Positive correlation between the LSMI and expression of CD40 in all DCs (r = 0.45; p = 0.04) was demonstrated. The MA was positively correlated with scavenger receptor CD36 [all DCs (r = 0.60; p = 0.01) and myeloid DCs (r = 0.63; p < 0.01)]. However, the MA was negatively correlated with CCR7 expression in all DCs (r = -0.46, p = 0.03.) and with CD83 [all DCs (r = -0.63; p = 0.01) and myeloid DCs (r = -0.75; p < 0.01)]. There were no relationships between the fat indexes and the DC phenotype. These results highlight a direct relationship between muscle depletion and changes in stimulatory, migratory and fatty acid-processing potential of DC in patients with CRC.

Increasing body condition score is positively associated interleukin-6 and monocyte chemoattractant protein-1 in Labrador retrievers.

The accumulation of excess body fat is a growing problem in dogs as well as people. Contrary to prior understanding of adipose tissue, fat is now considered to be an active endocrine organ that promotes a chronic low-grade inflammatory state often characterized by an increase in pro-inflammatory cytokines and chemokines. These have been implicated in several obesity-related disorders such as insulin resistance, cardiovascular disease, and neoplasia. The purpose of this study was to characterize fasting plasma cytokine concentrations in ninety-two healthy client-owned Labrador retriever dogs of various ages and body condition scores. The dogs were grouped according to body condition score (BCS) into three categories, lean, overweight and obese. The following cytokines and chemokines were evaluated; tumor necrosis factor-alpha, interleukin-2, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (TNF-α, IL-2, IL-6, IL-8, MCP-1). Our results indicated that fasting plasma IL-6 and MCP-1 concentrations are associated with increasing BCS. This data suggest that certain markers of inflammation increase with increasing body condition score, and that dogs, similar to humans, may be fostering a chronic inflammatory state due to obesity.

Evaluación nutricional e indicadores de grasa visceral y subcutánea en niños con síndrome de Down / Nutrition assessment and indicators of fat visceral and fat subcutaneous in children with Down syndrome

Antecedentes. Existen pocas publicaciones en relación a la composición corporal en niños con síndrome de Down (SD). Objetivos. Evaluar la relación entre los indicadores del estado nutricional (EN) -utilizando referencias catalanas y del CDC/NCHS- y los indicadores de la composición corporal, y comparar la concordancia entre los índices peso/talla (IP/T), índice de masa corporal/edad (IMC/E), y peso/edad (P/E) para evaluar el estado nutricional en niños con SD. Materiales y métodos. Estudio analítico de corte transversal en el que se estudiaron 40 niños con SD, 20 niñas y 20 niños de edades comprendidas entre 3 y 13 años. Se realizaron mediciones antropométricas para obtener indicadores del estado nutricional tales como IP/T, IMC/E y P/E, e indicadores de grasa visceral y subcutánea y del compartimiento muscular. Se evaluaron las pruebas de correlación y el índice de Kappa para establecer relación y concordancia, respectivamente. Resultados. La evaluación nutricional realizada en niños con SD muestra que el 60% presenta sobrepeso y obesidad, según el indicador IMC/E, porcentaje que alcanza el 75% según el índice IP/T. El análisis de correlación indica que la circunferencia de la cintura, el área de grasa braquial, y el % de masa grasa según Slaughter y Weststrate y Deurenberg, muestran una alta correlación positiva con el IMC/E (p < 0,05). Un modelo de regresión logística reflejó que ningún indicador de la masa grasa es clínicamente significativo para predecir el incremento del indicador P/E. Se determinó que los indicadores IMC/E e IP/T tienen una mayor concordancia (Kappa = 0,59; p = 0,0000). Conclusión. Determinamos una alta correlación entre el diagnóstico nutricional (IMC/E e IP/T) y los indicadores de las grasas visceral (circunferencia de la cintura) y subcutánea (porcentaje de masa grasa y de área grasa braquial) en niños con SD. Se encontró una mayor concordancia entre los indicadores de IMC/E e IP/T, lo que sugiere que estos son óptimos para evaluar el estado nutricional (AU)

Background: There are only few publications related to body composition in Down syndrome (DS). Objective: Evaluate the relationship between indicators of nutrition assessment by Catalan references and CDC/NCHS and indicators of body composition, and compare the concordance between weight/height index (IW/H), body mass index/age (BMI/A) and weight/age (W/A) to evaluate nutritional status in children with DS. Materials and methods: Analytical cross-sectional study in which 40 children with DS, 20 girls and 20 boys between 3 and 13 years old were studied. Anthropometric measurements were performed to obtain indicators of nutrition assessment as IW/H, BMI/A and W/A and indicators of subcutaneous and visceral fat and muscular compartment. Correlation tests and Kappa index were evaluated to establish relationship and agreement respectively. Results: The nutrition assessment in children with DS shows that 60% presents overweight and obesity according to BMI/A, and 75% according to IW/H. Correlation analysis indicates that waist circumference, fat brachial area, % fat mass by Slaughter and Weststrate and Deurenberg have a high positive correlation with BMI/A (p-value < 0.05). A logistic regression model showed that no indicator of fat mass is clinically significant in predicting an increase of the indicator W/A. It was determined that the BMI/A and IW/H indicators have a higher concordance (Kappa = 0.59; p =.0000). Conclusions: We determined a high correlation between nutritional diagnosis (BMI/A and IW/A) with indicators of visceral fat (waist circumference) and subcutaneous (% fat mass and fat brachial area) in children with DS. A greater agreement was found between indicators of BMI/A and IW/A suggesting that they are optimal for assessing the nutritional status (AU)

The Effects of Combined Exercise on Health-Related Fitness, Endotoxin, and Immune Function of Postmenopausal Women with Abdominal Obesity.

This study was conducted to examine the effects of combined exercise on health-related fitness, endotoxin concentrations, and immune functions of postmenopausal women with abdominal obesity. 20 voluntary participants were recruited and they were randomly allocated to the combined exercise group (n = 10) or the control group (n = 10). Visceral obesity was defined as a visceral-to-subcutaneous fat ratio ≥ 0.4 based on computed tomography (CT) results. Body composition, exercise stress testing, fitness measurement, CT scan, and blood variables were analyzed to elucidate the effects of combined exercise. The SPSS Statistics 18.0 program was used to calculate means and standard deviations for all variables. Significant differences between the exercise group and control group were determined with 2-way ANOVA and paired t-tests. The exercise group's abdominal obesity was mitigated due to visceral fat reduction; grip strength, push-ups, and oxygen uptake per weight improved; and HDL-C and IgA level also increased, while TNF-α, CD14, and endotoxin levels decreased. Lowered TNF-α after exercise might have an important role in the obesity reduction. Therefore, we can conclude that combined exercise is effective in mitigating abdominal obesity, preventing metabolic diseases, and enhancing immune function.

Classification of pro-inflammatory status for interleukin-6 affects relative muscle strength in obese elderly women.

BACKGROUND: Obesity, defined by an excess amount of body fat or a percent body fat higher than 30 % for women is a complex chronic disorder with multifactorial etiology and is accompanied by chronic low-grade inflammation, which results in elevated pro-inflammatory cytokines. AIMS: The aim of this study was to compare muscle strength between high and low pro-inflammatory status in obese elderly women and to verify the relationship of IL-6 with muscle strength and fat-free mass. METHODS: Eighty-nine elderly women (age 69.47 ± 6.07 years; body mass 64.70 ± 12.04 kg; height 1.52 ± 0.06 m; body mass index 27.78 ± 4.75 kg/m(2)) were divided into two groups: high and low inflammatory status for IL-6. Lower limb muscle strength was tested using bilateral leg extension with the ten repetitions maximum test, IL-6 was measured by ELISA and body composition by dual-energy X-ray absorptiometry. RESULTS: Women classified from the high pro-inflammatory status presented lower relative muscle strength (P = 0.056) when compared with the low inflammatory status group, with no differences for absolute muscle strength (P = 0.18). There was a significant negative correlation of IL-6 with relative muscle strength (P = 0.03, R = -0.22) and a considerable trend toward significance (P = 0.06, R = -0.19) and negative association with fat-free mass (P = 0.84, R = -0.02). CONCLUSIONS: This study provides insights that a high pro-inflammatory status in sedentary obese elderly women might impair muscle strength and negatively affect fat-free mass. Thus, elderly women classified with high pro-inflammatory status for IL-6 should receive further health care attention to prevent this deleterious condition.

Juvenile nutritional stress affects growth rate, adult organ mass, and innate immune function in zebra finches (Taeniopygia guttata).

Developmental conditions may influence many aspects of adult phenotype, including growth and immune function. Whether poor developmental environments impair both growth and immune function or induce a trade-off between the two processes is inconclusive, and the impact of the timing of stress in determining this relationship has so far been overlooked. We tested the hypothesis that the long-term effects of nutritional stress on growth, body composition, and immune function in zebra finches (Taeniopygia guttata) are different depending on whether stress is experienced during an early or a juvenile phase (i.e., before or after nutritional independence, respectively). We raised birds on high (H) or low (L) food conditions until posthatch day (PHD) 35 and switched treatments for half of the birds in each of the H and L groups from PHD 36 to 61. We found that unfavorable juvenile conditions (PHD 36-61) increased somatic growth rates and liver mass, body fat, and some aspects of immune function. We also observed a positive relationship between growth and immune function, as individuals that grew faster as juveniles also had better innate immune responses as adults. There was no effect of treatment on basal metabolic rate. These findings demonstrate the importance of juvenile developmental conditions in shaping multiple aspects of the adult phenotype.

Impact of protein supplementation and care and support on body composition and CD4 count among HIV-infected women living in rural India: results from a randomized pilot clinical trial.

Body composition in HIV-infected individuals is subject to many influences. We conducted a pilot 6-month randomized trial of 68 women living with AIDS (WLA) from rural India. High protein intervention combined with education and supportive care delivered by HIV-trained village women (activated social health activist [Asha] life [AL]) was compared to standard protein with usual care delivered by village community assistants (usual care [UC]). Measurements included CD4 counts, ART adherence, socio-demographics, disease characteristics (questionnaires); and anthropometry (bioimpedance analyzer). Repeated measures analysis of variance modeled associations. AL significantly gained in BMI, muscle mass, fat mass, ART adherence, and CD4 counts compared to UC, with higher weight and muscle mass gains among ART adherent (≥66%) participants who had healthier immunity (CD4 ≥450). BMI of WLA improved through high protein supplementation combined with education and supportive care. Future research is needed to determine which intervention aspect was most responsible.

Comparison of particle-exposure triggered pulmonary and systemic inflammation in mice fed with three different diets.

BACKGROUND: Obesity can be linked to disease risks such as diabetes and cardiovascular disorders, but recently, the adipose tissue (AT) macrophage also emerges as actively participating in inflammation and immune function, producing pro- and anti-inflammatory factors. Connections between the AT and chronic lung diseases, like emphysema and asthma and a protective role of adipocyte-derived proteins against acute lung injury were suggested.In this study we addressed the question, whether a diet challenge increases the inflammatory response in the alveolar and the blood compartment in response to carbon nanoparticles (CNP), as a surrogate for ambient/urban particulate air pollutants. METHODS: Mice were fed a high caloric carbohydrate-rich (CA) or a fat-rich (HF) diet for six weeks and were compared to mice kept on a purified low fat (LF) diet, respectively. Bronchoalveolar lavage (BAL) and blood samples were taken 24 h after intratracheal CNP instillation and checked for cellular and molecular markers of inflammation. RESULTS AND DISCUSSION: The high caloric diets resulted in distinct effects when compared with LF mice, respectively: CA resulted in increased body and fat mass without affecting blood cellular immunity. Conversely, HF activated the blood system, increasing lymphocyte and neutrophil counts, and resulted in slightly increased body fat content. In contrast to higher pro-inflammatory BAL Leptin in CA and HF mice, on a cellular level, both diets did not lead to an increased pro-inflammatory basal status in the alveolar compartment per se, nor did result in differences in the particle-triggered response. However both diets resulted in a disturbance of the alveolar capillary barrier as indicated by enhanced BAL protein and lactate-dehydrogenase concentrations. Systemically, reduced serum Adiponectin in HF mice might be related to the observed white blood cell increase. CONCLUSION: The increase in BAL pro-inflammatory factors in high caloric groups and reductions in serum concentrations of anti-inflammatory factors in HF mice, clearly show diet-specific effects, pointing towards augmented systemic inflammatory conditions. Our data suggest that extended feeding periods, leading to manifest obesity, are necessary to generate an increased susceptibility to particle-induced lung inflammation; although the diet-challenge already was efficient in driving pro-inflammatory systemic events.

Efeito da ração hiperlipídica e do extrato aquoso de erva-mate (Ilex paraguariensis) sobre a composição corporal e sobre a resposta inflamatória de macrófagos peritoniais de ratos Wistar / Effect of high-fat diet and yerba mate aqueous extract (Ilex paraguariensis) on body composition and on inflammatory response of peritonial macrophages in Wistar rats

Introdução - A inflamação está envolvida na patogênese da síndrome metabólica e de diversas doenças crônicas não transmissíveis (DCNT). Em macrófagos, a modulação da expressão gênica de mediadores inflamatórios está, em grande parte, sob o controle do fator de transcrição nuclear kappa B (NF-B), cuja atividade é modulada por diversos compostos bioativos presentes em alimentos. A erva-mate (Ilex paraguariensis) contém compostos bioativos, como o ácido cafeico, o kaempferol, a quercetina e o ácido 3,5-dicafeoilquínico, que apresentam a capacidade de reduzir a ativação do NF-B in vitro em macrófagos. Objetivo - Investigar os efeitos da ração hiperlipídica (HL) e da ingestão do extrato aquoso de erva-mate sobre a composição corporal e sobre a resposta inflamatória de macrófagos peritoniais de ratos Wistar. Métodos - Ratos Wistar, machos, foram submetidos à ração controle (n= 36) ou ração HL (n= 36) por 12 semanas. Após esse período, 12 animais de cada grupo foram eutanasiados, enquanto o restante foi distribuído em grupos que receberam ou não, por gavagem, o extrato aquoso de erva-mate durante o período de quatro semanas. Os resultados relativos ao efeito da ração HL foram comparados pelo test t de Student não pareado ou seu equivalente não-paramétrico (Mann-Whitney). Para a análise do efeito da erva-mate, utilizou-se a análise de variância (ANOVA, post-hoc de Tukey) ou seu equivalente não-paramétrico (teste de Kruskal-Wallis, post-hoc de Dunn). Adotou-se como nível de significância p < 0,05. Resultados - Após 12 semanas, o consumo de ração HL resultou em aumento significativo do ganho de peso, de gordura corporal e do índice HOMA (Homeostasis Model Assessment) (p < 0,05). Não foi observada alteração dos biomarcadores sistêmicos de inflamação, como o fator de necrose tumoral (TNF)-, a interleucina (IL)-6 e o inibidor do ativador de plasminogênio (PAI)-1. Em relação aos ensaios envolvendo macrófagos peritoniais, observou-se capacidade reduzida de síntese de IL-1, IL-6, óxido nítrico (NO) e IL-10 nas células dos animais com ração HL, quando estimuladas com LPS (p < 0,05). Tal fenômeno foi acompanhado por diminuição da fosforilação da quinase do inibidor do B (IKK)-, da degradação do inibidor do B (IB)- e da ativação do NF-B (p < 0,05). A ingestão do extrato aquoso de erva-mate atenuou o ganho de peso e de gordura corporal e reduziu as concentrações plasmáticas de insulina, TNF- e IL-6 (p < 0,05).

Effects of exercise combined with caloric restriction on inflammatory cytokines.

Chronic inflammation has been implicated in the pathogenesis of several chronic diseases, such as atherosclerosis and diabetes, as well as certain types of cancers. It has been suggested that circulating biomarkers for inflammation may be modified by exercise; however, few laboratory-based studies have been conducted in nonobese premenopausal women. The purpose of this investigation was to determine the impact of a 4-month exercise training and caloric-restriction intervention with the goal of weight loss on circulating biomarkers of inflammation in sedentary premenopausal women aged 25- 40 years (weight, 57 ± 2 kg). Subjects were studied for 6 consecutive menstrual cycles: 1 Screening, 1 Baseline, then 4 interventions (Interventions 1-4). Supervised aerobic training, consisting primarily of treadmill running and elliptical machine exercise, was performed 4 times per week for 40-90 min at 79% ± 0.7% of maximal heart rate. Subjects also consumed 30% fewer calories vs. baseline (1863 ± 58 to 1428 ± 53 kcalday(-1) (1 kcal = 4.186 kJ), p < 0.0001). Circulating inflammatory biomarkers, including adiponectin, high-sensitivity (hs) C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and leptin, as well as body composition, aerobic capacity, and energy balance, were measured before and after the intervention. Maximal aerobic capacity increased by 8.5 ± 1.7 mL kg(-1)min-1 (p < 0.001) and body mass declined by an average of 3.7 ± 0.5 kg (p < 0.001). Significant reductions in IL-6 (0.39 ± 0.04 to 0.30 ± 0.03 pgmL(-1), p = 0.025), IFN-γ (0.58 ± 0.83 to 0.42 ± 0.64 pgmL-1, p = 0.030), and leptin (13.18 ± 1.28 to 6.28 ± 0.71 pgmL(-1), p < 0.001) were detected in response to the intervention. No significant changes in adiponectin, hs-CRP, or TNF-α were found. Weight loss in response to exercise training and caloric restriction is effective in reducing inflammatory markers, specifically IL-6 and leptin.

Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants.

OBJECTIVES: Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD). STUDY DESIGN: This cross-sectional study was performed in a tertiary care center. METHODS: Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual. RESULTS: Compared with controls, obese patients had lower free T3 levels and free T4 levels (P<0.01), greater prevalence of hypothyroidism (P<0.05), and higher commonness of antithyroid antibodies (P<0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent in the obese group (P<0.01). Correlation analysis showed that leptin levels were associated with AITD (P<0.01) independent of bioanthropometric variables. Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD. CONCLUSIONS: Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.

A 12-week supplementation with quercetin does not affect natural killer cell activity, granulocyte oxidative burst activity or granulocyte phagocytosis in female human subjects.

Quercetin, a flavonoid found in fruits and vegetables, is a strong antioxidant with anti-inflammatory, antimicrobial and immune-modulating properties. The purpose of the present study was to investigate the effects of long-term quercetin supplementation on innate immune function and inflammation in human subjects. Female subjects (n 120; aged 30-79 years) were recruited from the community and randomised to one of three groups, with supplements administered using double-blinded procedures: 500 mg quercetin/d (n 38), 1000 mg quercetin/d (n 40) or placebo (n 42). Subjects ingested two soft chew supplements twice daily during the 12-week study period. Fasting blood samples were obtained pre- and post-study and were analysed for plasma quercetin, IL-6, TNF-alpha and leucocyte subset cell counts. Natural killer cell activity (NKCA) and lymphocyte subsets were assessed in a subset of seventy-four subjects. Granulocyte oxidative burst activity (GOBA) and phagocytosis were assessed in sixty-four subjects. Eighteen subjects had overlapping data. Quercetin supplementation at two doses compared with placebo increased plasma quercetin (interaction effect; P < 0.001) but had no significant influence on blood leucocyte subsets, plasma IL-6 or TNF-alpha concentration, NKCA, GOBA or phagocytosis. NKCA was inversely correlated with BMI (r - 0.25; P = 0.035) and body fat percentage (r - 0.38; P = 0.001), and positively correlated with self-reported physical fitness level (r 0.24; P = 0.032). In summary, results from the present double-blinded, placebo-controlled, randomised trial indicated that quercetin supplementation at 500 and 1000 mg/d for 12 weeks significantly increased plasma quercetin levels but had no influence on measures of innate immune function or inflammation in community-dwelling adult females.

The periparturient relaxation of immunity in Merino ewes infected with Trichostrongylus colubriformis: endocrine and body compositional responses.

The temporal association between the periparturient rise in worm egg count of grazing Merino ewes to infection with Trichostrongylus colubriformis and the underlying causal mechanisms was investigated in an experiment that incorporated two levels of pregnancy (pregnant or unmated), two levels of infection (infected with 6000 T. colubriformis L(3)/week or uninfected) and, following lambing, three levels of lactation (non-lactating/"dry", early-weaned 2 days after parturition, or suckled). In addition to parasitological and host immune responses reported in a previous paper (Beasley et al., 2010), a range of endocrine and body compositional changes were monitored from day -50 to day 42, relative to the midpoint of lambing (day 0). By day -19, pregnant ewes had begun to mobilise fat and eye muscle, and after 42 days of suckling had lost 31% and 8%, respectively, of their existing depots. In comparison to non-pregnant (dry) ewes, the endocrine profiles of late-pregnant ewes were characterised by low levels of cortisol and prolactin and high levels of progesterone and oestradiol. Lactating ewes had lower levels of cortisol and leptin and higher levels of prolactin compared to both dry and early-weaned ewes. The mobilisation of fat and protein reserves throughout lactation in suckled ewes was closely associated with leptin and cortisol profiles, and provided strong evidence of an underlying nutritional basis for the periparturient relaxation of immunity. Both leptin and cortisol concentrations were also associated with both parasite burden and the immune status of the ewe. It is suggested that lower blood cortisol levels in suckled ewes contribute to a Th1 biased immune response that leads to an increased susceptibility to gastrointestinal nematodes. The results provide a detailed characterisation of the physiology underlying the periparturient relaxation of immunity to T. colubriformis, from which further investigations will aim to expose potential causal factors.

Impact of adiposity on immunological parameters.

Studies evaluating immune function in obese humans and experimental animals indicate that the excess adiposity is associated with impaired in immune responses. Obesity is related to a higher rate of infections and to some types of cancer. Nutritional, metabolic and endocrine factors are implicated in the immunological changes. The adipose tissue directly produces substances with various functions related to immune system. Furthermore, some investigations suggest that certain types of weight reduction strategies can alter the immune function. Nevertheless, long-term studies should be carried out to address whether these changes positively affects the ability of these obese individuals to control infections and tumor development.

Impact of adiposity on immunological parameters / Impacto da adiposidade nos parâmetros imunológicos

Studies evaluating immune function in obese humans and experimental animals indicate that the excess adiposity is associated with impaired in immune responses. Obesity is related to a higher rate of infections and to some types of cancer. Nutritional, metabolic and endocrine factors are implicated in the immunological changes. The adipose tissue directly produces substances with various functions related to immune system. Furthermore, some investigations suggest that certain types of weight reduction strategies can alter the immune function. Nevertheless, long-term studies should be carried out to address whether these changes positively affects the ability of these obese individuals to control infections and tumor development.

Estudos acerca da função imunológica em animais experimentais e humanos obesos indicam que o excesso de adiposidade associa-se ao prejuízo da resposta imune. A obesidade está relacionada a uma taxa maior de infecções e a alguns tipos de câncer. Fatores nutricionais, metabólicos e endócrinos estão implicados nessas alterações imunológicas. O próprio tecido adiposo produz diretamente substâncias com várias funções relacionadas ao sistema imune. Além disso, algumas investigações sugerem que certas estratégias para perda de peso podem alterar a função imune. Entretanto, estudos em longo prazo são necessários para avaliar se tais alterações afetam positivamente a capacidade desses pacientes obesos de controlar infecções e desenvolver tumores.