Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nano emulsions.

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

Role of carotenoids in adipose tissue through the AMPK-mediated pathway.

Diet is a critical factor in controlling adiposity and white adipose tissue (WAT) physiology. A high-fat diet (HFD) alters WAT function and affects AMP-activated protein kinase (AMPK) - a cellular sensor - dysregulating lipolysis and lipid metabolism in adipocytes. Otherwise, AMPK activation may attenuate oxidative stress and inflammation. Interest in natural therapies, such as carotenoid consumption or supplementation, is growing due to their health benefits. Carotenoids are lipophilic pigments present in vegetables and fruits, which cannot be synthesized by the human body. Interventions focused on ameliorating complications induced by a HFD indicate a positive contribution of the carotenoids to the AMPK activation. This review aims to outline the mechanism of carotenoids in the AMPK pathway in adipose tissue and their contribution in regulating adipogenesis. Different carotenoids can act as an agonist of the AMPK signaling pathway, activating upstream kinases, upregulating transcriptional factors, inducing WAT browning, and blocking adipogenesis. In addition, the improvement of some "homeostatic" factors, such as adiponectin, may mediate the AMPK activation induced by carotenoids. With these findings, we encourage clinical trials to confirm the role of carotenoids in the AMPK pathway in a long-term treatment, mainly in obesity cases.

Proanthocyanidins in grape seeds and their role in gut microbiota-white adipose tissue axis.

Several factors can impact the gut microbiota, affecting host metabolism and immunity. It implies intestinal barrier disruption and translocation of gut microbiota metabolites to the bloodstream, such as lipopolysaccharides (LPS). LPS is an endotoxin from gram-negative gut bacteria that trigger the activation of the Toll-like receptor-4 (TLR-4) inflammatory pathway and can modulate white adipose tissue (WAT) metabolism. Dietary components, including diets rich in fiber and polyphenols, contribute to intestinal environment homeostasis. Grape seed proanthocyanidins extract (GSPE) may improve intestinal permeability and microbial diversity and increase short-chain fatty acids production. Furthermore, GSPE has been involved in LPS reduction, down-regulating the TLR-4 pathway, decreasing the WAT metainflammatory profile, and preventing adipocyte hypertrophy. Studies have pointed out strategies to promote health and control obesity by modulating the gut microbiota environment. Therefore, this review aims to summarize the potential effects of GSPE on the gut microbiota-white adipose tissue axis against obesity.

The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity. / O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar.

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.

O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar / The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity

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.

Semi-intensive and Intensive Interdisciplinary Treatments Have Similar Effects on Metabolic Syndrome and Selected Inflammatory Markers in Adolescents with Obesity.

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.

Adipocytokine and appetite-regulating hormone response to weight loss in adolescents with obesity: Impact of weight loss magnitude.

OBJECTIVE: The aim of this study was to investigate the association between the magnitude of weight loss (WL) and serum concentrations of the main adipocytokines and appetite-regulating hormones in adolescents with obesity. METHODS: After completion of informed consent,108 adolescents with obesity (14-19 y of age; postpubertal) were submitted to clinical, nutritional, psychological, physical exercise, and physiotherapy support for 1 y. Body composition (BC) and plasma levels of neuropeptides (neuropeptide Y [NPY], agouti-related peptide [AgRP], and α-melanocyte-stimulating hormone [α-MSH]) and leptin were measured at baseline and post-intervention. RESULTS: After therapy, adolescents who lost <10% body weight and <10% body weight (were compared. Both groups presented improvements in BC and reduced leptin. The Δα-MSH, Δα-MSH/AgRP ratio, and Δα-MSH/NPY ratio were lower and AgRP and NPY variations were higher in the low weight loss group. The leptin concentration was close to normal in the high weight loss only. The ΔWeight, Δα-MSH and Δleptin were associated with body fat loss by multiple linear regressions for all samples. CONCLUSION: Weight loss >10% seems to reverse obesity-induced hyperleptinemia while stabilizing the neuropeptides that control appetite in adolescents with obesity. We were able to produce a prognostic mathematical model to predict body fat loss using weight, leptin, and α-MSH variations.

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity

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.

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity.

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.

An Interdisciplinary Weight Loss Program Improves Body Composition and Metabolic Profile in Adolescents With Obesity: Associations With the Dietary Inflammatory Index.

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.

The Long-Term Impact of High Levels of Alpha-Melanocyte-Stimulating Hormone in Energy Balance Among Obese Adolescents.

BACKGROUND: Deregulation of orexigenic and anorexigenic pathways occurs among adolescents with obesity. Alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis and an important anorexigenic neuropeptide in the control of energy balance and thermogenesis. However, it was not well explored if α-MSH can modulate long-term weight loss therapy responses in a dependent manner according to its concentration. Our hypothesis is that a high α-MSH concentration at baseline promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents. METHODS: One hundred ten post-pubertal obese adolescents (body mass index >95th percentile) were submitted to 1 year of interdisciplinary therapy (clinical, nutritional, psychological, physical exercise, and physiotherapy support). Body composition and plasma levels of α-MSH, neuropeptide Y (NPY), melanin-concentrating hormone, and agouti-related peptide (AgRP) were measured before and after therapy. The volunteers were grouped on the basis of Tertiles of α-MSH concentration: Low (<0.75 ng/mL), Medium (≤0.76 to ≥1.57 ng/mL), and High (>1.57 ng/mL). Significance was set as p < 0.05. RESULTS: The treatment promoted a significant improvement in body adiposity and fat free mass for all groups. It is important to note that only in the high α-MSH group, a significant increase of the α-MSH/NPY ratio and decrease NPY/AgRP ratio post treatment were observed. CONCLUSION: The high α-MSH concentration promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents following long-term weight loss therapy and this is important in clinical practice.