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1.
Int J Endocrinol ; 2023: 7625720, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37101600

RESUMO

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

2.
Arq Bras Cardiol ; 118(1): 33-40, 2022 Jan.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35195206

RESUMO

BACKGROUND: The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. OBJECTIVE: To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. METHODS: 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. RESULTS: Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. CONCLUSION: This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.


FUNDAMENTO: A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. OBJETIVO: Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. MÉTODOS: 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). RESULTADOS: Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. CONCLUSÃO: Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.


Assuntos
Doenças Cardiovasculares , Síndrome Metabólica , Obesidade Infantil , Adolescente , Fator Natriurético Atrial/metabolismo , Composição Corporal , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Criança , Humanos , Síndrome Metabólica/epidemiologia , Obesidade Infantil/terapia , Redução de Peso/fisiologia
3.
Arq. bras. cardiol ; Arq. bras. cardiol;118(1): 33-40, jan. 2022. tab, graf
Artigo em Inglês, Português | LILACS | ID: biblio-1360114

RESUMO

Resumo Fundamento A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. Objetivo Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. Métodos 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). Resultados Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. Conclusão Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.


Abstract Background The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. Objective To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. Methods 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. Results Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. Conclusion This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.


Assuntos
Humanos , Criança , Adolescente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Síndrome Metabólica/epidemiologia , Obesidade Infantil/terapia , Composição Corporal , Redução de Peso/fisiologia , Índice de Massa Corporal , Fator Natriurético Atrial/metabolismo
4.
J Obes Metab Syndr ; 30(4): 386-395, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34966004

RESUMO

BACKGROUND: The purpose of the present study was to compare the impact of semi-intensive and intensive interdisciplinary weight-loss therapies on the treatment of metabolic syndrome (MS) and selected inflammatory markers in adolescents with obesity. METHODS: The study included 166 adolescents enrolled in two groups for 22 weeks: the intensive group (in-person aerobic and resistance exercise three times a week, and psychological and nutritional counselling once a week), or the semi-intensive group (six in-person exercise orientation meetings and six in-person psychological support sessions with an online nutritional and exercise program). Anthropometric parameters, blood pressure, fasting glucose, insulin, lipid profile, triglycerides (TG), leptin and adiponectin were assessed before and after the interventions. RESULTS: Body weight and waist circumference decreased in both groups (P<0.001) and large effect sizes (η2= 0.586 and η2=0.465, respectively) were noted. Significant time and group interactions were found (P=0.001) with medium effect sizes (η2=0.095 and η2=0.105, respectively). The prevalence of MS decreased from 27.9% to 13.1% (P=0.012) and 29.4% to 5.9% (P=0.004) in the semi-intensive and intensive groups, respectively. All MS risk factors decreased significantly over time (P<0.001) and a significant time*group interaction was observed (P<0.05), except for fasting TG (P=0.832) and glucose (P=0.128, η2=0.021). CONCLUSION: The results suggested that both approaches promoted significant clinical improvement in the condition of adolescents with MS and reduced associated risk factors. Studies that consider the cost effectiveness of both treatments are still needed to determine whether semi-intensive care, with its lower financial costs, may be a suitable option to treat obesity and MS in adolescents with obesity.

5.
Arch. endocrinol. metab. (Online) ; 65(6): 821-831, Nov.-Dec. 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1349997

RESUMO

ABSTRACT Objective: To investigate the effects of an interdisciplinary intervention on biomarkers of inflammation and their relationship with fibroblast growth factor 21 (FGF21) concentrations in women with overweight and obesity. Subjects and methods: Thirty-one women were enrolled in a 12-week interdisciplinary weight loss program delivered by a team comprising an endocrinologist, nutritionist and exercise physiologist. Body composition; anthropometric measures; metabolic and inflammatory markers including adiponectin, leptin, and atrial natriuretic peptide (ANP) were assessed at baseline and post-therapy. The homeostasis model assessment of insulin resistance (HOMA-IR) and the homeostasis model assessment of adiponectin (HOMA-AD) were calculated. The participants were divided into two groups: those with increased FGF21, and those with decreased FGF21. Results: The sample comprised women aged 32 ± 5 years with a body mass index of 33.64 ± 3.49 kg/m2. Body weight, waist circumference and leptin concentration were decreased in the whole sample after therapy. However, only the group with an increase in FGF21 concentration presented significant improvements in adiponectin concentration and adiponectin/leptin ratio. Moreover, although there was a reduction of leptin in both groups, it was greater in the increased FGF21 groups. There was a reduction in ANP in the decreased FGF21 group. Conclusions: Changes in FGF21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels. Furthermore, improvements in adiponectin and the adiponectin/leptin ratio were found only in the group with increased FGF21 concentration.


Assuntos
Humanos , Feminino , Adulto , Programas de Redução de Peso , Obesidade/terapia , Resistência à Insulina , Biomarcadores/sangue , Índice de Massa Corporal , Leptina , Adiponectina , Fatores de Crescimento de Fibroblastos/sangue
6.
Arch Endocrinol Metab ; 65(6): 821-831, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34762789

RESUMO

OBJECTIVE: To investigate the effects of an interdisciplinary intervention on biomarkers of inflammation and their relationship with fibroblast growth factor 21 (FGF21) concentrations in women with overweight and obesity. METHODS: Thirty-one women were enrolled in a 12-week interdisciplinary weight loss program delivered by a team comprising an endocrinologist, nutritionist and exercise physiologist. Body composition; anthropometric measures; metabolic and inflammatory markers including adiponectin, leptin, and atrial natriuretic peptide (ANP) were assessed at baseline and post-therapy. The homeostasis model assessment of insulin resistance (HOMA-IR) and the homeostasis model assessment of adiponectin (HOMA-AD) were calculated. The participants were divided into two groups: those with increased FGF21, and those with decreased FGF21. RESULTS: The sample comprised women aged 32 ± 5 years with a body mass index of 33.64 ± 3.49 kg/m2. Body weight, waist circumference and leptin concentration were decreased in the whole sample after therapy. However, only the group with an increase in FGF21 concentration presented significant improvements in adiponectin concentration and adiponectin/leptin ratio. Moreover, although there was a reduction of leptin in both groups, it was greater in the increased FGF21 groups. There was a reduction in ANP in the decreased FGF21 group. CONCLUSION: Changes in FGF21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels. Furthermore, improvements in adiponectin and the adiponectin/leptin ratio were found only in the group with increased FGF21 concentration.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Obesidade , Sobrepeso , Programas de Redução de Peso , Adiponectina , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Humanos , Resistência à Insulina , Leptina , Obesidade/terapia , Sobrepeso/terapia
7.
J Sports Med Phys Fitness ; 61(2): 280-286, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32720782

RESUMO

BACKGROUND: We investigated the impact of obesity on responses to high intensity interval exercise (HIIE) on hunger and energy intake (EI) in young men. METHODS: Ten men with obesity (OB) (Body Mass Index [BMI]: 34.6±4.4 kg/m2) and 10 with normal weight (CG) (BMI: 23.1±3.9 kg/m2) participated in a HIIE session. The session consisted of 6 rounds performed at 100% of maximum aerobic velocity (MAV) for 30 seconds, followed by 30 seconds of active recovery at 50% MAV and concluded with 4 minutes of passive recovery. This was repeated three times. EI was estimated at baseline and 24 h-post-HIIE. Hunger was measured at baseline, 2 h- and 24 h-post HIIE. RESULTS: Carbohydrate (CHO) intake increased in both groups (P<0.01). Hunger feelings (19.5 [0-50] mm at baseline to 50 [9-73] mm post-2 h and 60 [8-92] mm in post-24 h [group: P=0.71, time: P<0.01, group × time: P=0.06]) and a desire to eat (34 [1-89] ±36.0 mm at baseline to 63 [11-86] mm post-2 h and 51 [7-84] mm post-24 h [group: P=0.65, time: P<0.01, group × time: P=0.29]) increased in both groups. CONCLUSIONS: Weight status does not modulate hunger and EI post-HIIE. However, the compensatory increase in CHO intake and hunger feelings is particularly noteworthy for health professionals.


Assuntos
Comportamento Alimentar/fisiologia , Treinamento Intervalado de Alta Intensidade , Obesidade/terapia , Adulto , Índice de Massa Corporal , Ingestão de Energia , Exercício Físico/fisiologia , Humanos , Fome , Masculino
8.
Arch. endocrinol. metab. (Online) ; 64(4): 479-482, July-Aug. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1131118

RESUMO

ABSTRACT Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.


Assuntos
Humanos , Adolescente , Redução de Peso , Fatores de Crescimento de Fibroblastos/sangue , Obesidade , Metabolismo Energético , Tecido Adiposo Branco
9.
Arch Endocrinol Metab ; 64(4): 479-482, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32267352

RESUMO

Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Obesidade , Redução de Peso , Tecido Adiposo Branco , Adolescente , Metabolismo Energético , Humanos
11.
Nutr Metab Cardiovasc Dis ; 30(4): 683-693, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32008915

RESUMO

BACKGROUND AND AIMS: Pediatric obesity and sleep-disordered breathing (SDB) are associated with cardiometabolic risk (CMR), but the degree of severity at which SDB affects cardiometabolic health is unknown. We assessed the relationship between the CMR and the apnea-hypopnea index (AHI), to identify a threshold of AHI from which an increase in the CMR is observed, in adolescents with obesity. We also compared the clinical, cardiometabolic and sleep characteristics between adolescents presenting a high (CMR+) and low CMR (CMR-), according to the threshold of AHI. METHODS AND RESULTS: 114 adolescents with obesity were recruited from three institutions specialized in obesity management. Sleep and SDB as assessed by polysomnography, anthropometric parameters, fat mass (FM), glucose and lipid profiles, and blood pressure (BP) were measured at admission. Continuous (MetScoreFM) and dichotomous (metabolic syndrome, MetS) CMR were determined. Associations between MetScoreFM and AHI adjusted for BMI, sex and age were assessed by multivariable analyses. Data of 82 adolescents were analyzed. Multivariable analyses enabled us to identify a threshold of AHI = 2 above which we observed a strong and significant association between CMR and AHI (Cohen's d effect-size = 0.57 [0.11; 1.02] p = 0.02). Adolescents with CMR+ exhibited higher MetScoreFM (p < 0.05), insulin resistance (p < 0.05), systolic BP (p < 0.001), sleep fragmentation (p < 0.01) and intermittent hypoxia than CMR- group (p < 0.0001). MetS was found in 90.9% of adolescents with CMR+, versus 69.4% in the CMR- group (p < 0.05). CONCLUSIONS: The identification of a threshold of AHI ≥ 2 corresponding to the cardiometabolic alterations highlights the need for the early management of SDB and obesity in adolescents, to prevent cardiometabolic diseases. CLINICAL TRIALS: NCT03466359, NCT02588469 and NCT01358773.


Assuntos
Metabolismo Energético , Pulmão/fisiopatologia , Síndrome Metabólica/etiologia , Obesidade Infantil/complicações , Respiração , Síndromes da Apneia do Sono/etiologia , Sono , Adiposidade , Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Brasil , Feminino , França , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Obesidade Infantil/sangue , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Medição de Risco , Fatores de Risco , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia
12.
Front Nutr ; 6: 77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214594

RESUMO

Background and Aims: The prevalence of overweight and obesity consitutes a global epidemic and it is growing around the world. Food and nutrition are essential requirements for promoting health and protecting against non-communicable chronic diseases, such as obesity and cardiovascular disease. Specific dietary components may modulate inflammation and oxidative stress in obese individuals. The Dietary Inflammatory Index (DII®) was developed to characterize the anti- and pro-inflammatory effects of individuals' diet. Few studies have investigated the role of diet-associated inflammation in adolescents with obesity. The present study aims to investigate the effects of an interdisciplinary weight loss therapy on DII scores and cardiometabolic risk in obese adolescents and possibles correlations. Methods: A total of 45 volunteers (14-19 years old) were recruited and enrolled for long-term interdisciplinary therapy including clinical, nutritional, psychological counseling, and exercise training. Adolescents had access to videos about health education weekly. Body composition and inflammatory and serum profiles were evaluated at baseline and after intervention. The food intake was obtained by 24-h food recall. Data was used to calculate energy-adjusted DII (E-DII) scores. Negative scores indicate an anti-inflammatory diet and positive scores indicates a pro-inflammatory diet. The sample was divided according to whether individuals increased or decreased E-DII scores after therapy. Results: After therapy the body mass index (BMI), body weight, body fat, abdominal, waist, neck, and hip circumferences decreased significantly. The mean of high-density lipoprotein cholesterol (HDL-c) increased after the therapy. There was found an improvement of inflammatory and cardiometabolic parameters. In exploratory analyses, this occurred mainly when the EDII improved. Conclusion: Long-term interdisciplinary therapy combined with a health education website improved inflammatory serum markers in obese adolescents. Reduction in DII scores was associated with reduction of cardiometabolic parameters, suggesting that an anti-inflammatory diet may be an effective strategy to prevent and treat obesity and related comorbidities. Trial: http://www.ensaiosclinicos.gov.br/rg/RBR-6txv3v/, Register Number: RBR-6txv3v.

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