Adipose Tissue, Non-Communicable Diseases, and Physical Exercise: An Imperfect Triangle.

The study of adipose tissue has received considerable attention due to its importance not just in maintaining body energy homeostasis but also in playing a role in a number of other physiological processes. Beyond storing energy, adipose tissue is important in endocrine, immunological, and neuromodulatory functions, secreting hormones that participate in the regulation of energy homeostasis. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favoring the secretion of deleterious adipocytokines that induce a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases and even some types of cancer. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity, with emphasis on hypocaloric diets and exercise. The aim of this review is to examine the pathophysiological mechanisms of obesity, considering the relationship among adipose tissue and two aspects that contribute positively or negatively to keeping a healthy body homeostasis, namely, exercise and noninfectious diseases. We conclude that the relationship of these aspects does not have homogeneous effects among individuals. Nevertheless, it is possible to establish some common mechanisms, like a decrease in pro-inflammatory markers in the case of exercise, and an increase in chronic inflammation in non-communicable diseases. An accurate diagnosis might consider the particular variables of a patient, namely their molecular profile and how it affects its metabolism, routines, and lifestyle; their underling health conditions; and probably even the constitution of their microbiome. We foresee that the development and accessibility of omics approaches and precision medicine will greatly improve the diagnosis, treatment, and successful outcomes for obese patients.

Longitudinal Study of Plasma Visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) Levels in Healthy Pregnant Women.

Visfatin/nicotinamide phosphorybosil transferase (NAMPT) is a novel adipocytokine with potential roles in the pathophysiology of metabolic disorders, including gestational disorders. However, there is no clear interpretation regarding the circulating visfatin levels in a healthy pregnancy. Therefore, we conducted the first longitudinal study of plasma visfatin levels that followed up healthy pregnant women until the third trimester, including the postpartum period (PPP). The study recruited healthy women with singleton pregnancy who were not using any drug (including tobacco and alcohol). We have excluded pregnant women who did not attend all scheduled exams and developed gestational diabetes or hypertension, obesity, preeclampsia, or any infections during pregnancy. Nine women were considered eligible and examined during all three trimesters of pregnancy and between 8 and 12 weeks postpartum (PPP). Visfatin/NAMPT concentrations were measured in EDTA-plasma by ELISA. The mean age of pregnant women included was 22±5 years (54% primiparous), and the mean of gestational age at delivery was 40±1.2 weeks. Mean systolic and diastolic blood pressures were 90 and 70 mmHg, respectively. Mean values (± standard error mean) of visfatin concentrations (µg/L) during trimesters were 11.38±1.45 (first, 11-14 weeks), 9.18±1.82 (second, 20-24 weeks), 18.67±2.65 (third, 34-36 weeks), and 10.12±1.49 in the PPP. The value of the third trimester was significantly higher than the second trimester, and significantly reduced in the PPP (p<0.05, ANOVA with Bonferroni's multiple comparison tests). Visfatin/NAMPT levels are significantly lower in the PPP, suggesting that factors stimulating its production would be limited to pregnancy, thereby contributing to its potential application as a biomarker in pregnancy complications.

Efeito do jejum agudo no período ativo sobre os peptídeos gastrointestinais em mulheres eutróficas e com obesidade / Effect of acute fasting in the active period on gastrointestinal peptides in women eutrophic and with obesity

A prática do jejum tem mostrado resultados benéficos no que diz respeito aos parâmetros metabólicos e perda de peso. Essa prática tem sido frequentemente realizada ao longo do dia, durante as atividades de vida diária dos indivíduos. Dentre os efeitos do jejum sobre o metabolismo intermediário, destaca-se seu potencial em modular a secreção de peptídeos gastrointestinais relacionados ao controle da fome e regulação metabólica. Por outro lado, é desconhecido os efeitos do jejum agudo durante as atividades de vida diária, diferentemente do realizado durante a noite, e ainda se indivíduos eutróficos e com obesidade respondem da mesma forma. Objetivo: Investigar o efeito do jejum agudo realizado durante o período ativo sobre os peptídeos gastrointestinais em mulheres eutróficas e com obesidade. Métodos: Trata-se de ensaio clínico não randomizado, estratificado por estado nutricional em dois grupos de acordo com o Índice de Massa Corporal (IMC): (i) grupo eutrófico (IMC > 18,5 kg/m² e < 24,9 kg/m²) e (ii) grupo obesidade (IMC > 35 kg/m²). A amostra foi composta por mulheres adultas, com idade entre 18 a 60 anos. A avaliação inicial foi realizada no período da manhã, após 10h de jejum noturno, em que as seguintes medidas foram aferidas e os dados pessoais foram coletados: antropometria, calorimetria indireta e composição corporal. As participantes foram submetidas à coleta de 5 mL de sangue, para análise dos peptídeos gastrointestinais (GIP, GLP-1, PP, PYY e grelina), adiponectina, insulina (glicose e índices HOMA). Em seguida, foi ofertado desjejum padronizado com valor calórico correspondente a 20% da necessidade energética estimada calculada após a coleta dos dados iniciais. Após, as voluntárias foram dispensadas para realização das atividades diárias habituais e foi orientado a manutenção do jejum por 10h ao longo do dia. As voluntárias retornaram ao final do dia para repetição dos procedimentos realizados na primeira avaliação e coleta de sangue. As análises estatísticas foram efetuadas com o auxílio dos programas Statistical Package for the Social Sciences for Windows Student Version® (SPSS) versão 20.0 e os gráficos foram criados por meio do programa GraphPad Prism versão 8.0.1, adotando-se nível de significância de 5%. Resultados: 54 mulheres foram incluídas no estudo, sendo 29 no grupo eutrófico e 25 no grupo com obesidade. O jejum no período ativo promoveu redução nas concentrações de insulina e adiponectina e nos índices HOMA-IR e HOMA-BETA, além de aumento no polipeptídeo pancreático (PP) circulante, tanto nas mulheres eutróficas como nas mulheres com obesidade. Somente o grupo com obesidade teve redução na leptina e aumento no peptídeo-1 semelhante ao glucagon (GLP-1) após o jejum diurno. Entre os grupos, eutrofia versus obesidade, as concentrações de leptina e insulina foram maiores no grupo obesidade após o jejum no período ativo. Já os peptídeos GIP, grelina e peptídeo YY (PYY) não tiveram mudanças após o jejum no período ativo quando comparados ao jejum noturno. Conclusão: O jejum durante as atividades diárias diminui os hormônios anorexígenos insulina e leptina. No entanto, também aumenta o PP e o GLP-1, especialmente em mulheres com obesidade. O jejum durante as atividades diárias pode reorganizar uma intrincada rede de sinais endócrinos que de alguma forma podem modular o comportamento alimentar homeostático e hedônico.

Fasting practice has shown beneficial results concerning metabolic parameters and weight loss. This practice is often performed throughout the day during individuals daily life activities. Among the effects of fasting on intermediary metabolism, its potential to modulate the secretion of gastrointestinal peptides related to hunger control and metabolic regulation stands out. On the other hand, the effects of acute fasting during daily activities, unlike fasting during the night, and whether eutrophic and individuals with obesity respond in the same way are unknown. Objective: To investigate the effect of acute fasting during the active period on gastrointestinal peptides in eutrophic women and with obesity. Methods: This was a non-randomized clinical trial, stratified by nutritional status into two groups according to Body Mass Index (BMI): (i) eutrophic group (BMI > 18.5 kg/m² and < 24.9 kg/m²) and (ii) group with obesity (BMI > 35 kg/m²). The sample consisted of adult women aged 18 to 60 years. The initial evaluation was conducted in the morning after a 10-hour overnight fasting, during which the following measurements were taken, and personal data were collected: anthropometry, indirect calorimetry, and body composition. Participants had 5 mL of blood collected for the analysis of gastrointestinal peptides (GIP, GLP-1, PP, PYY, and ghrelin), adiponectin, insulin (glucose and HOMA indices). Then, a standardized breakfast with a caloric value corresponding to 20% of the estimated energy needs calculated after the initial data collection was provided. Afterward, the participants were released to perform their usual daily activities and were instructed to maintain fasting for 10 hours throughout the day. Participants returned at the end of the day for the repetition of the procedures performed in the initial assessment and blood collection. Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows Student Version® (SPSS) version 20.0, and the graphs were created using the GraphPad Prism version 8.0.1 program, adopting a significance level of 5%. Results: 54 women were included in the study, with 29 in the eutrophic group and 25 in the group with obesity. Fasting during the active period led to a reduction in insulin and adiponectin concentrations and in HOMA-IR and HOMA-BETA indices, as well as an increase in circulating pancreatic polypeptide (PP), both in eutrophic women and with obesity. Only the group with obesity experienced a reduction in leptin and an increase in glucagon-like peptide-1 (GLP-1) after daytime fasting. Between the eutrophic group and with obesity, leptin and insulin concentrations were higher in the group with obesity after fasting during the active period. GIP, ghrelin, and peptide YY (PYY) did not show changes after fasting during the active period when compared to overnight fasting. Conclusion: Fasting during daily activities reduces anorexigenic hormones insulin and leptin. However, it also increases PP and GLP-1, especially in women with obesity. Fasting during daily activities may reorganize a complex network of endocrine signals that can somehow modulate homeostatic and hedonic eating behavior.

The addition of different oils in the diet regulates the expression of adipocytokine signaling genes in sheep longissimus dorsi muscle.

Nutrition is an important factor that regulates the expression of several genes. The aim of this work was to analyze the effects of diets containing additions of different oils on the regulation of the adipocytokine signaling gene expressions in sheep longissimus dorsi muscle. Forty males and non-neutered sheep were kept in individual cages and fed under four different treatments: control treatment (concentrate and forage) and the other three treatments containing the concentrate and forage plus 4% oil (yellow grease, soybean and palm oils). After slaughter, samples of the longissimus dorsi muscle were collected. RNA extraction followed by Real Time PCR for five adipocytokine signaling genes. ANOVA was performed followed by the Dunnett's test (0.01). The normalized expressions of the ACLY gene were not significant between treatments to control, but for the ALDOC gene, all oil-supplemented treatments were significantly downregulated relative to the control treatment. The DUSP gene was not significantly expressed between the oil-supplemented treatments to control treatment. The ENPP1 gene was significantly upregulated with the addition of palm oil and yellow grease and the FASN gene was only significantly expressed in soybean oil-supplemented treatment to control treatment. It was concluded that the addition of different oils in the sheep diet regulated the expression of most genes for up or down, which can influence the metabolic pathways responsible for the fatty acid biosynthesis in the sheep longissimus dorsi muscle.

Low miR-222 expression in human visceral adipose tissue is associated with insulin resistance and PTEN and p53 mRNA levels.

INTRODUCTION: The aim of this is study was to analyse the expression of miR-193b, miR-378, miR-Let7-d, and miR-222 in human visceral adipose tissue (VAT), as well as their association with obesity, insulin resistance (IR), and their role in the regulation of genes controlling adipose tissue homeostasis, including adipocytokines, the phosphatase and tension homologue (PTEN), and tumour protein 53 (p53). MATERIAL AND METHODS: VAT was obtained from normal-weight (NW), overweight, and obese (OW/OB) subjects with and without IR. Stem-loop RT-qPCR was used to evaluate miRNA expression levels. miRTarBase 4.0, miRWalk, and DIANA-TarBase v8 were used for prediction of validated target gene of the miRNA analysed. A qPCR was used to evaluate PTEN, p53, leptin (LEP), and adiponectin (ADIPOQ) mRNA. RESULTS: miR-222 was lower in IR subjects, and miR-222 and miR-378 negatively correlated with HOMA-IR. PTEN and p53 are miR-222 direct targets according to databases. mRNA expression of PTEN and p53 was lower in OW/OB subjects with and without IR, compared to NW group and its levels positively associated with miR-222. Additionally, p53 and PTEN are positively associated with serum leptin levels. On the other hand, miR-193b and miR-378 negatively correlated with serum leptin but not with mRNA levels. Moreover, miR-Let-7d negatively correlated with serum adiponectin but not with adiponectin mRNA levels. CONCLUSIONS: Lower miR-222 levels are associated with IR, and PTEN and p53 expression; the implication of these genes in adipose tissue homeostasis needs more research.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old.

Insulin levels, adipocytokines, and inflammatory mediators trigger benign breast disease (BBD) and breast cancer (BC). The relationship between serum adipocytokines levels, overweight-obesity, metabolic disturbs, and BC is unclear. Methods: To analyze the serum levels of the adipocytokines, insulin, and the HOMA IR in women without breast disease, with BBD or BC, and the role of these as risk factors for benign breast disease or breast cancer. Results: Adipsin values > 0.91 and visfatin levels > 1.18 ng/mL represent a risk factor to develop BBD in NBD lean women (OR = 18; and OR = 12). Data in overweight-obese women groups confirm the observation due to insulin levels > 2.6 mU/mL and HOMA IR > 0.78, with OR = 60.2 and 18, respectively; adipsin OR = 26.4, visfatin OR = 12. Breast cancer risk showed a similar behavior: Adipsin risk, adjusted by insulin and visfatin OR = 56 or HOMA IR and visfatin OR = 22.7. Conclusion: Adipose tissue is crucial for premalignant and malignant tissue transformation in women with overweight-obesity. The adipocyte−breast epithelium interaction could trigger a malignant transformation in a continuum, starting with BBD as premalignant disease, especially in overweight-obese women.

Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity.

Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction.

Hyperresistinemia in Obese Female Dogs With Mammary Carcinoma in Benign-Mixed Tumors and Its Correlation With Tumor Aggressiveness and Survival.

Resistin is associated with metabolic, inflammatory, and neoplastic disorders, and is also considered a prognostic marker in human oncology. Canine mammary tumors have epidemiological, clinical, biological, and genetic characteristics similar to those of women and are proposed as a comparative study model. Here, we evaluate the serum levels of resistin in female dogs with or without mammary carcinoma in mixed tumors (CBMT) and its correlation with the proliferative potential of the tumor, obesity, and survival. Eighty dogs grouped according to the presence (50) or absence (30) of CBMT, reproductive status and body condition were assessed for weight, fat percentage, and canine body mass index. The characteristic of the proliferative potential of the tumor (Ki-67) was evaluated. Ki-67 levels (p = 0.024), staging (p = 0.004), and grade (p = 0.016) influenced the survival of the female dogs. Through a multifactorial analysis, it could be seen that the parameters proliferation index (Ki-67) (p = 0.044) and staging (p = 0.036) influenced the survival of the animals. Neutered and overweight dogs from the control and CBMT groups showed hyperresistinemia. Ki-67 expression and resistin levels in dogs with CBMT were higher in overweight dogs than in dogs with normal weight (p = 0.0001). The survival rate of dogs with CBMT, obese and with high levels of resistin (8,400 µg L-1) was lower when compared to those with lower levels of resistin. These results showed an important relationship between hyperresistinemia, tumor proliferative potential and excessive body fat, suggesting that resistin levels may act as an interesting prognostic marker in patients with CBMT.

Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs / Marcadores de inflamação e resistência à insulina em cães antes e depois da perda de peso versus cães saudáveis e magros

Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.(AU)

A inflamação crônica de baixo grau na obesidade é caracterizada pela produção aumentada de citocinas pró-inflamatórias que contribuem para a resistência à insulina. Para este estudo a composição corporal e os marcadores de inflamação e de resistência à insulina em cães antes e após a perda de peso foram comparados aos de cães magros. Onze cães adultos obesos pertencentes a tutores foram incluídos em um programa de perda de peso com ração comercial hipocalórica e alcançaram escore de condição corporal (ECC) ideal seis meses após o início do regime. Um Grupo Controle de nove cães com ECC ideal foi selecionado para a comparação. O teste de Shapiro-Wilk foi usado para testar a normalidade, Mann Whitney foi usado para análise dos dados que não atenderam distribuição normal e o teste t de Student foi usado para parâmetros que atenderam a normalidade. No Grupo Obesidade, a gordura corporal diminuiu de 41,6% (30,7-58,6) para 29,1% (18,6-46,3) (P<0,01) e os cães mantiveram massa magra ao longo do programa de perda de peso (P>0,05). Cães obesos apresentaram maior concentração de frutosamina, triglicérides, insulina, IGF-1 e leptina do que o Grupo Controle antes da redução de peso (P<0,05). As concentrações séricas de triglicerídeos, IL-2, IL-6, TNF-α, insulina, leptina e IGF-1 diminuíram após a perda de peso (P<0,01) e, essas concentrações foram semelhantes ao Grupo Controle (P>0,05), com exceção da leptina (P<0,001). Nenhuma alteração no peptídeo YY foi encontrada. As concentrações de leptina (r=0,60; P=0,01), frutosamina (r=0,44; P=0,02) e triglicerídeos (r=0,40; P=0,04) correlacionaram-se com a redução da gordura corporal. A perda de peso reduziu as concentrações de marcadores inflamatórios e de resistência à insulina e a maioria dos parâmetros tornaram-se semelhante aos dos cães que sempre foram magros, reforçando a importância da perda de peso na prática clínica de pequenos animais.(AU)

Markers of inflammation and insulin resistance in dogs before and after weight loss versus lean healthy dogs / Marcadores de inflamação e resistência à insulina em cães antes e depois da perda de peso versus cães saudáveis e magros

Chronic low-grade inflammation in obesity is characterized by an increased production of pro-inflammatory cytokines that contribute to insulin resistance. For this study body composition, markers of inflammation and of insulin resistance in dogs before and after weight loss were compared to those of lean dogs. Eleven client-owned obese adult dogs underwent a weight loss program with commercial dry food for weight loss and reached an ideal body condition score (BCS) six months after the beginning of the weight loss program. A Control Group of nine dogs with ideal BCS were selected for the comparison. Shapiro-Wilk test was used to test for normality, Mann Whitney were used for non-normally distributes data, and Student t-test was used for normally distributed parameters. In the Obese Group body fat decreased from 41.6% (30.7-58.6) to 29.1% (18.6-46.3) (P<0.01) and dogs maintained lean body mass throughout the weight loss program (P>0.05). Obese dogs presented higher concentration of fructosamine, triglycerides, insulin, IGF-1 and leptin than the Control Group before weight reduction (P<0.05). Serum concentrations of triglycerides, IL-2, IL-6, TNF-α, insulin, leptin and IGF-1 decreased after weight loss (P<0.01), and these concentrations were similar to the Control Group (P>0.05), except for leptin (P<0.001). No alteration on peptide YY was found. Leptin (r=0.60, P=0.01), fructosamine (r=0.44, P=0.02) and triglycerides (r=0.40, P=0.04) concentrations correlated with the reduction of body fat. Weight loss reduced the concentrations of inflammatory and insulin resistance markers and most parameters became similar to dogs that have always been lean, reinforcing the importance of weight loss in small animal practice.(AU)

A inflamação crônica de baixo grau na obesidade é caracterizada pela produção aumentada de citocinas pró-inflamatórias que contribuem para a resistência à insulina. Para este estudo a composição corporal e os marcadores de inflamação e de resistência à insulina em cães antes e após a perda de peso foram comparados aos de cães magros. Onze cães adultos obesos pertencentes a tutores foram incluídos em um programa de perda de peso com ração comercial hipocalórica e alcançaram escore de condição corporal (ECC) ideal seis meses após o início do regime. Um Grupo Controle de nove cães com ECC ideal foi selecionado para a comparação. O teste de Shapiro-Wilk foi usado para testar a normalidade, Mann Whitney foi usado para análise dos dados que não atenderam distribuição normal e o teste t de Student foi usado para parâmetros que atenderam a normalidade. No Grupo Obesidade, a gordura corporal diminuiu de 41,6% (30,7-58,6) para 29,1% (18,6-46,3) (P<0,01) e os cães mantiveram massa magra ao longo do programa de perda de peso (P>0,05). Cães obesos apresentaram maior concentração de frutosamina, triglicérides, insulina, IGF-1 e leptina do que o Grupo Controle antes da redução de peso (P<0,05). As concentrações séricas de triglicerídeos, IL-2, IL-6, TNF-α, insulina, leptina e IGF-1 diminuíram após a perda de peso (P<0,01) e, essas concentrações foram semelhantes ao Grupo Controle (P>0,05), com exceção da leptina (P<0,001). Nenhuma alteração no peptídeo YY foi encontrada. As concentrações de leptina (r=0,60; P=0,01), frutosamina (r=0,44; P=0,02) e triglicerídeos (r=0,40; P=0,04) correlacionaram-se com a redução da gordura corporal. A perda de peso reduziu as concentrações de marcadores inflamatórios e de resistência à insulina e a maioria dos parâmetros tornaram-se semelhante aos dos cães que sempre foram magros, reforçando a importância da perda de peso na prática clínica de pequenos animais.(AU)

Alliin, an Allium sativum Nutraceutical, ReducesMetaflammation Markers in DIO Mice.

Obesity generates a chronic low-grade inflammatory state which promotes oxidativestress and triggers comorbidities. Alliin is the main organosulfur compound in garlic and has beenshown to induce a decrease in the expression of proinflammatory cytokines; its systemic effect onmetabolic parameters and adipose tissue is not yet known, however. After nine weeks of HFD andwith obesity established in C57BL/6 mice, we observed that a daily treatment with alliin for 3.5weeks (15 mg/kg) did not affect body weight, but significantly improved insulin sensitivity andglucose tolerance, both evaluated through a blood glucose monitoring system. Once alliin treatmentwas completed, serum, adipose tissue, and organs of interest related to metabolism were removedfor further analysis. We observed that alliin significantly decreased the size of adipocytes fromepididymal adipose tissue, evaluated via microscopy. A decrease in gene expression and serumprotein levels of the adipocytokines leptin and resistin, as well as decreased serum IL-6concentration, were detected by qRT-PCR and ELISA, respectively. It did not, however, affectmRNA expression of antioxidant enzymes in the liver. Taken altogether, these results indicate thattreatment with alliin reduces metaflammation markers in DIO mice and improves some metabolicparameters without affecting others.

The relationship between chronic inflammation associated with obesity and vitamin D deficiency / Relación entre inflamación crónica asociada a obesidad y déficit de vitamina D

Obesity is characterized by an abnormal production of adipocytokines, generating chronic inflammation associated in turn with endothelial dysfunction, atherosclerosis and insulin resistance. On the other hand, it is a risk factor for vitamin D deficiency, thus establishing an inverse relationship between the plasma levels of this nutrient and acute phase proteins with low vitamin D levels, being able to boost the inflammatory response in obesity. In this context, the correction of poor vitamin D status could be an effective addition to the treatment of obesity; however, evidence of future trials that can support the regulatory effects of supplementation is required. The objective of this review is to analyze the existing evidence and establish the relationship between plasma levels of vitamin D and chronic inflammation associated with obesity. The methodology consists of a sensitive search in the PubMed and Trip Database, limiting the search to articles in English and Spanish published through January 2019. Priority was given to clinical trials, original articles and systematic reviews, from which other relevant research was identified.

La obesidad se caracteriza por la producción anormal de adipocitocinas, generando inflamación crónica asociada a su vez a disfunción endotelial, aterosclerosis y resistencia a insulina. Por otra parte, es un factor de riesgo de déficit de vitamina D, estableciéndose una relación inversa entre los niveles plasmáticos de dicho nutriente y proteínas de fase aguda, pudiendo potenciar la respuesta inflamatoria en obesidad. En este contexto la corrección del mal estado de vitamina D podría ser una adición efectiva al tratamiento de la obesidad, sin embargo se requiere evidencia de futuros ensayos que se puedan respaldar los efectos reguladores de la suplementación. El objetivo de esta revisión es analizar la evidencia existente y establecer la relación entre los niveles plasmáticos de vitamina D y la inflamación crónica asociada con la obesidad. La metodología consiste en una búsqueda sensible en las bases de datos PubMed y Trip Database, limitándose la búsqueda a artículos en inglés y español hasta enero 2019. Se priorizó por ensayos clínicos, artículos originales y revisiones sistemáticas, a partir de los cuales se identificaron otras investigaciones relevantes.

Adipocytokines and High Blood Pressure in Mexican Children.

Given that adipocytokines may play an important role in the pathophysiology of high blood pressure (HBP) and because related reports in children are scarce and controversial, we evaluated the relationship of leptin, resistin, tumor necrosis factor-α, interleukin-6, adiponectin, and interferon-γ with HBP. Materials and Methods. A total of 129 (53.8%) girls and 111 (46.2%) boys, with average ages of 10.8 ± 0.9 and 10.6 ± 1.0 years, respectively, were enrolled in a cross-sectional study. HBP was defined by systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) between the 90th and 95th percentiles. A multivariate logistic regression backwards-stepwise analysis adjusted for body mass index, waist circumference, and triglyceride levels was performed to compute the association between adipocytokines and HBP. Results. Seventy-two (30.0%) participants showed HBP: 44 (61.1%) girls and 28 (38.9%) boys. Multivariate analysis showed that, irrespective of obesity, serum levels of adiponectin, but not those of other adipocytokines, are inversely associated with HBP (odds ratio 0.93; 95% CI 0.77 to 0.98, p = .04). Conclusions. Our results show that low serum adiponectin levels, but not those of other adipocytokines, are inversely associated with HBP; this association is independent of obesity.

Associations of ADIPOQ and LEP Gene Variants with Energy Intake: A Systematic Review.

This systematic review aims to evaluate the association of adiponectin (ADIPOQ) and leptin (LEP) gene variants with energy intake. Cross-sectional, cohort, and case⁻control studies that reported an association of leptin and/or adiponectin gene variants with energy intake were included in this review. Human studies without any age restrictions were considered eligible. Detailed individual search strategies were developed for each of the following bibliographic databases: Cochrane, Latin American and Caribbean Center on Health Sciences Information (LILACS), PubMed/MEDLINE, Scopus, and Web of Science. Risk of bias assessment was adapted from the Downs and Black scale and was used to evaluate the methodology of the included studies. Seven studies with a pooled population of 2343 subjects were included. The LEP and ADIPOQ gene variants studied were LEP-rs2167270 (k = 1), LEP-rs7799039 (k = 5), ADIPOQ-rs2241766 (k = 2), ADIPOQ-rs17300539 (k = 1), and ADIPOQ marker D3S1262 (k = 1). Two of the seven studies reviewed demonstrated a positive association between the LEP-rs7799039 polymorphism and energy intake. Two other studies-one involving a marker of the ADIPOQ gene and one examining the ADIPOQ-rs17300539 polymorphism-also reported associations with energy intake. More research is needed to further elucidate the contributions of genetic variants to energy metabolism.

Neck circumference is associated with non-traditional cardiovascular risk factors in individuals at low-to-moderate cardiovascular risk: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Neck circumference (NC) is associated with traditional cardiovascular risk factors (CVRF), but its usefulness to identify earlier atherogenic risk has been scarcely examined. Associations of NC with non-traditional CVRF were investigated in participants at low-to-moderate risk from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: 807 individuals (35-54 years) without obesity, diabetes or cardiovascular disease was stratified into quartiles of NC (cut-off for men: 36.5; 37.9 and 39.5 cm; women: 31.4; 32.5 and 34 cm) and traditional and non-traditional risk factors (lipoprotein subfractions by Vertical Auto Profile, adiponectin, leptin, E-selectin) were compared across groups. In linear regression models, associations of NC with non-traditional risk factors were tested for the entire sample and for low-risk group (≤ 2 CVRF). RESULTS: In both sexes, BMI, waist circumference, systolic and diastolic blood pressure, fasting and 2-h plasma glucose, HOMA-IR, triglycerides, leptin, E-selectin, small dense LDL-cholesterol, IDL-cholesterol, VLDL3-cholesterol and TG/HDL ratio increased significantly, while HDL2-cholesterol and HDL3-cholesterol decreased across NC quartiles. In linear regression models, a direct association [ß(95% CI)] of NC with leptin [(0.155 (0.068-0.242); 0.147 (0.075-0.220)], E-selectin [(0.105 (0.032-0.177); 0.073 (0.006 to 0.140)] and small-dense LDL [(1.866 (0.641-3.091); 2.372 (1.391-3.353)] and an inverse association with HDL2-cholesterol [(- 0.519 (- 0.773 to - 0.266); - 0.815 (- 1.115 to 0.515)] adjusted for age were detected for men and women, respectively. CONCLUSION: Our findings indicate that measurement of NC may be useful for an earlier identification of unfavorable atherogenic metabolic profile in middle-aged individuals at lower cardiovascular risk level.

Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy.

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T. cruzi-seropositive (asymptomatic or with CCC) and sero-negative individuals were studied. Serum tumour necrosis factor (TNF)-α, interleukin (IL)-6, adipocytokines and the expression of their receptors in peripheral blood mononuclear cell (PBMC) were evaluated, together with other factors influencing the immune response. CCC patients showed major metabolic and hormonal abnormalities, in parallel with increased IL-6 and leptin serum levels. TNF-α receptor s, leptin and adiponectin receptors (ObR and Adipo-Rs respectively), as well as PPAR-γ expression in PBMCs from CCC patients were compatible with a counteracting response leading to an unfavourable immune-metabolic profile. These results suggest that persistently increased levels of immune-metabolic pro-inflammatory mediators along with the adverse endocrine anti-inflammatory response of CCC individuals, may contribute to the underlying mechanisms dealing with myocardial tissue damage.

Metalloproteinases in non-alcoholic fatty liver disease and their behavior in liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is a clinical entity of high prevalence in the world characterized by fatty infiltration of liver tissue in the absence of alcohol consumption. The natural history of the disease develops in successive phases reflected in different histological stages, with 10-20% of patients developing liver cirrhosis and fibrosis. Fibrosis is a basic connective tissue lesion defined by the increase of the fibrillary extracellular matrix (ECM) components in a tissue or organ. Matrix metalloproteinases (MMPs) constitute a family of endopeptidases, which are involved in ECM and basement membranes components degradation. Fibrogenic process is characterized by altered ECM composition, associated with modifications in MMPs behavior. The active cross-talk between adipose tissue and liver can be altered in pathologies associated to insulin resistance (IR), such as NAFLD. The role of adipokines on MMPs behavior in the liver could be partly responsible of liver damage during IR. The aim of this revision is to describe the behavior of MMPs in NAFLD and its role in the associated fibrosis.

Imunolocalização de receptores de leptina no ovário de preás (Galea spixii Wagler, 1831) / Immunolocalization of leptin receptor of Spix's Yellow-toothed Cavy (Galea spixii Wagler, 1831) ovary

A leptina, uma citocina produzida pelas células adiposas, é alvo da comunidade científica por acreditarem que ela apresente impacto sobre a reprodução dos animais promovendo a puberdade, foliculogênese e oogênese, ciclo estral e auxiliando na fecundação. A compreensão dos mecanismos que controlam a atividade reprodutiva de preás (Galea spixii) possui papel relevante para a preservação da espécie. Desta forma, o presente trabalho propôs analisar a imunolocalização dos receptores de leptina (Ob-R) no ovário de preás. Coletaram-se os ovários de 20 fêmeas adultas, não prenhes e saudáveis. As amostras foram fixadas em paraformaldeído a 4% em tampão fosfato, incluídas em parafina e seccionadas para a realização de imunohistoquímica (IHC). As secções foram fotomicrografadas e avaliadas quanto à intensidade da reação. Observou-se forte imunorreação no oócito e nas células da teca, moderada nas células do estroma ovariano e nas células luteínicas grandes e fracamente coradas nas células da granulosa, endoteliais, perivasculares e células luteínicas pequenas. Quando comparado a expressão de receptores ao longo do desenvolvimento folicular foi observado que o oócito e as células da teca se mantiveram com expressão na mesma intensidade. Entretanto, as células da granulosa apresentaram forte marcação nos estádios pré-antrais enquanto que nos folículos antrais apresentou fraca intensidade. Concluímos que em ovários de Galea spixii existe a presença de Ob-R nas principais estruturas do ovário sugerindo que este hormônio desempenhe papel fundamental na reprodução desta espécie.(AU)

Leptin, a cytokine produced by adipose cells, is the target of the scientific community for believing that it has an impact on the reproduction of the animals promoting puberty, folliculogenesis and oogenesis, estrous cycle and aiding in fertilization. The understanding of the mechanisms controlling the reproductive activity of Spix's Yellow-toothed Cavy (Galea spixii) plays a relevant role in the preservation of the species. Thus, the present study proposed to analyze the immunolocalization of leptin receptors (Ob-R) in the ovary of cavies. Ovaries from 20 adult, non-pregnant, healthy females were collected. The samples were fixed in 4% phosphate buffered paraformaldehyde, embedded in paraffin and sectioned for immunohistochemistry. The sections were photomicrographs and intensity of the reaction was measured. Strong immunoreaction was observed in oocyte and theca cells, moderate in ovarian stromal cells and large luteal cells and weak stained in granulosa, endothelial, perivascular and small luteal cells. When compared to receptor expression along follicular development it was observed that the oocyte and the theca cells remained with expression at the same intensity. However, the granulosa cells presented strong stained in the preantral stages, whereas in the antral follicles it presented low intensity. We conclude that in the ovaries of Galea spixii there is the presence of Ob-R in the main structures of the ovary sugesting that this hormone plays a fundamental role in the reproduction of this species.(AU)

Imunolocalização de receptores de leptina no ovário de preás (Galea spixii Wagler, 1831) / Immunolocalization of leptin receptor of Spix's Yellow-toothed Cavy (Galea spixii Wagler, 1831) ovary

A leptina, uma citocina produzida pelas células adiposas, é alvo da comunidade científica por acreditarem que ela apresente impacto sobre a reprodução dos animais promovendo a puberdade, foliculogênese e oogênese, ciclo estral e auxiliando na fecundação. A compreensão dos mecanismos que controlam a atividade reprodutiva de preás (Galea spixii) possui papel relevante para a preservação da espécie. Desta forma, o presente trabalho propôs analisar a imunolocalização dos receptores de leptina (Ob-R) no ovário de preás. Coletaram-se os ovários de 20 fêmeas adultas, não prenhes e saudáveis. As amostras foram fixadas em paraformaldeído a 4% em tampão fosfato, incluídas em parafina e seccionadas para a realização de imunohistoquímica (IHC). As secções foram fotomicrografadas e avaliadas quanto à intensidade da reação. Observou-se forte imunorreação no oócito e nas células da teca, moderada nas células do estroma ovariano e nas células luteínicas grandes e fracamente coradas nas células da granulosa, endoteliais, perivasculares e células luteínicas pequenas. Quando comparado a expressão de receptores ao longo do desenvolvimento folicular foi observado que o oócito e as células da teca se mantiveram com expressão na mesma intensidade. Entretanto, as células da granulosa apresentaram forte marcação nos estádios pré-antrais enquanto que nos folículos antrais apresentou fraca intensidade. Concluímos que em ovários de Galea spixii existe a presença de Ob-R nas principais estruturas do ovário sugerindo que este hormônio desempenhe papel fundamental na reprodução desta espécie.

Leptin, a cytokine produced by adipose cells, is the target of the scientific community for believing that it has an impact on the reproduction of the animals promoting puberty, folliculogenesis and oogenesis, estrous cycle and aiding in fertilization. The understanding of the mechanisms controlling the reproductive activity of Spix's Yellow-toothed Cavy (Galea spixii) plays a relevant role in the preservation of the species. Thus, the present study proposed to analyze the immunolocalization of leptin receptors (Ob-R) in the ovary of cavies. Ovaries from 20 adult, non-pregnant, healthy females were collected. The samples were fixed in 4% phosphate buffered paraformaldehyde, embedded in paraffin and sectioned for immunohistochemistry. The sections were photomicrographs and intensity of the reaction was measured. Strong immunoreaction was observed in oocyte and theca cells, moderate in ovarian stromal cells and large luteal cells and weak stained in granulosa, endothelial, perivascular and small luteal cells. When compared to receptor expression along follicular development it was observed that the oocyte and the theca cells remained with expression at the same intensity. However, the granulosa cells presented strong stained in the preantral stages, whereas in the antral follicles it presented low intensity. We conclude that in the ovaries of Galea spixii there is the presence of Ob-R in the main structures of the ovary sugesting that this hormone plays a fundamental role in the reproduction of this species.