SH2B1 variants as potential causes of non-syndromic monogenic obesity in a Brazilian cohort.

PURPOSE: SH2B1 gene encodes an important adaptor protein to receptor tyrosine kinases or cytokine receptors associated with Janus kinases. This gene has been associated with the structural and functional modulation of neurons and other cells, and impacts on energy and glucose homeostasis. Several studies suggested that alterations in this gene are strong candidates for the development of obesity. However, only a few studies have screened SH2B1 point variants in individuals with obesity. Therefore, the aim of this study was to investigate the prevalence of SH2B1 variants in a Brazilian cohort of patients with severe obesity and candidates to bariatric surgery. METHODS: The cohort comprised 122 individuals with severe obesity, who developed this phenotype during childhood. As controls, 100 normal-weight individuals were included. The coding region of SH2B1 gene was screened by Sanger sequencing. RESULTS: A total of eight variants were identified in SH2B1, of which p.(Val345Met) and p.(Arg630Gln) variants were rare and predicted as potentially pathogenic by the in the silico algorithms used in this study. The p.(Val345Met) was not found in either the control group or in publicly available databases. This variant was identified in a female patient with severe obesity, metabolic syndrome and hyperglycemia. The p.(Arg630Gln) was also absent in our control group, but it was reported in gnomAD with an extremely low frequency. This variant was observed in a female patient with morbid obesity, metabolic syndrome, hypertension and severe binge-eating disorder. CONCLUSION: Our study reported for the first time two rare and potentially pathogenic variants in Brazilian patients with severe obesity. Further functional studies will be necessary to confirm and elucidate the impact of these variants on SH2B1 protein function and stability, and their impact on energetic metabolism. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Association of the MC4R rs17782313 polymorphism with plasma ghrelin, leptin, IL6 and TNFα concentrations, food intake and eating behaviors in morbidly obese women.

PURPOSE: The rs17782313 variant of the MC4R gene plays an important role in the obesity phenotype. Studies that evaluate environmental factors and genetic variants associated with obesity may represent a great advance in understanding the development of this disease. This work seeks to assess the association of the polymorphism of MC4R rs17782313 on plasma parameters, including leptin, ghrelin, tumor necrosis factor (TNFα) and interleukin 6 (IL6), and on the eating behaviors of morbidly obese women. METHODS: 70 adult women with BMI between 40 and 60 kg/m2 were recruited. Laboratory and anthropometric data were recorded. Using a visual analog scale (VAS), the feelings of hunger and satiety were evaluated. The presence or absence of binge eating was evaluated through the Binge Eating Scale (BES) questionnaire. Habitual food intake was analyzed using 3-day dietary records. TaqMan® assays were conducted using real-time PCR to assess genotype polymorphism variants from peripheral blood DNA. RESULTS: This study found that female patients with the MC4R rs17782313 polymorphism had high levels of ghrelin and reduced levels of IL6 in the postprandial period. We observed a higher prevalence of severe binge eating in more than 50% of women with at least one risk allele. CONCLUSION: Our hypothesis is that the MC4R rs17782313 polymorphism may influence the release of ghrelin, even without being associated with feelings of hunger and satiety. More than half of women with this polymorphism exhibited severe binge eating. LEVEL OF EVIDENCE: Level III: case-control analytic study.

Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients.

PURPOSE: Monogenic forms of obesity are caused by single-gene variants which affect the energy homeostasis by increasing food intake and decreasing energy expenditure. Most of these variants result from disruption of the leptin-melanocortin signaling, which can cause severe early-onset obesity and hyperphagia. These mutation have been identified in genes encoding essential proteins to this pathway, including leptin (LEP), melanocortin 2 receptor accessory proteins 2 (MRAP2) and proopiomelanocortin (POMC). We aimed to investigate the prevalence of LEP, MRAP2 and POMC rare variants in severely obese adults, who developed obesity during childhood. To the best of our knowledge, this is the first study screening rare variants of these genes in patients from Brazil. METHODS: A total of 122 Brazilian severely obese patients (BMI ≥ 35 kg/m2) were screened for the coding regions of LEP, MRAP2 and POMC by Sanger sequencing. All patients are candidates to the bariatric surgery. Clinical characteristics were described in patients with novel and/or potentially pathogenic variants. RESULTS: Sixteen different variants were identified in these genes, of which two were novel. Among them, one previous variant with potentially deleterious effect in MRAP2 (p.Arg125Cys) was found. In addition, two heterozygous mutations in POMC (p.Phe87Leu and p.Arg90Leu) were predicted to impair protein function. We also observed a POMC homozygous 9 bp insertion (p.Gly99_Ala100insSerSerGly) in three patients. No pathogenic variant was observed in LEP. CONCLUSION: Our study described for the first time the prevalence of rare potentially pathogenic MRAP2 and POMC variants in a cohort of Brazilian severely obese adults. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Food intake of women with gestational diabetes mellitus, in accordance with two methods of dietary guidance: a randomised controlled clinical trial.

The aim of the study was to evaluate the food intake of pregnant women with gestational diabetes mellitus (GDM) according to two methods of dietary guidance. A randomised controlled clinical trial was conducted by appointment with a nutritionist and by using data from hospital records (2011-2014). The study population comprised adult women diagnosed with GDM treated in a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received nutritional advice by the traditional method and the intervention group (IG) were instructed on carbohydrate counting. The analysis of food intake and the consumption of processed foods (PF) and ultra-processed foods (UPF) were evaluated in the second and third trimester. A total of 286 pregnant women were initially assessed (145 in the CG and 141 in the IG). It was observed that 89/120 (74·2 %) and 183/229 (79·9 %) consumed PF daily in the second and third trimesters, respectively, whereas 117/120 (97·5 %) and 225/231 (97·4 %) consumed UPF daily in the second and third trimesters, respectively. When analysing the intake of macronutrients (%) by quartiles, women who had fat intake in the third quartile had the highest average postprandial blood glucose compared with those who consumed fat in the second quartile (P=0·02). The consumption of PF and UPF was high and dietary intake was similar in both groups, regardless of dietary guidance method deployed, suggesting that both methods tested in the study can be used for monitoring the nutritional status of pregnant women with GDM.

Monounsaturated fat-rich diet reduces body adiposity in women with obesity, but does not influence energy expenditure and substrate oxidation: a parallel randomized controlled clinical trial.

BACKGROUND: Obesity is an important and growing health problem whose treatment involves dietary changes. In this context, studying the role of macronutrients in weight loss is required in order to understand which strategies may be applied for weight loss. We aimed to evaluate the effects of diets rich in polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on resting energy expenditure (REE), substrate oxidation, and weight loss in women with obesity. METHODS: Randomized, controlled, single blind, parallel-group clinical trial was conducted for 60 days. Participants (n = 32) were divided into three groups: G1= normocaloric PUFAs-rich diet (12% of total energy expenditure (TEE), 10% of n-6 and up to 2% of n-3); G2= normocaloric MUFAs-rich diet (15-20% TEE); and G3= maintenance of the usual diet. Anthropometric and metabolic variables (REE and substrate oxidation by indirect calorimetry) were evaluated. RESULTS: G2 decreased body weight (-1.92 ± 1.99 kg, P = 0.02), body mass index (BMI) (-0.69 ± 0.70 kg/m2; P = 0.02), waist circumference (WC) (-1.91 ± 1.82 cm; P = 0.02), and body fat (-1.14 ± 1.53 kg; P = 0.04). CONCLUSION: MUFAs-rich diet reduces body weight, BMI, body fat, and WC. CLINICAL TRIALS: NCT02656940. CLINICAL TRIAL REGISTRATION: Clinical Trials: NCT02656940.

Profile of Gut Microbiota of Adults with Diabetes Mellitus Type 1: A Systematic Review.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic disease of clinical importance, whose prevalence has increased in Brazil and worldwide. Among the possible factors involved in the genesis and control of the disease, the intestinal microbiota (IM) deserves to be highlighted, but studies that report differences between the IM of patients with T1DM and those who are healthy are still contradictory and scarce. OBJECTIVE: The objective of this paper was to evaluate the IM profile of T1DM and healthy patients, in order to verify possible differences and to evaluate the possibility of the influence of IM on glycemic control in T1DM. METHODS: Of the 2716 articles found, nine were included in this review, and all of which were randomized, observational, cross-sectional, cohort and case-control studies that characterized the composition of IM in adults with T1DM and healthy adults. RESULTS: Studies are very diverse, which makes it difficult to associate the IM profile with T1DM etiology and control, however it was found that there was a prevalence of the phylum Firmicutes in the IM of individuals with T1DM and that there was no significant difference in the relative abundance of Bacteroidetes in both populations. CONCLUSION: It was also possible to identify an inverse relationship of the genus Bifidobacterium and a positive relationship of the genera Bacteroidetes and Prevotella with the concentration ofglycated hemoglobin. More studies are needed to contemplate the characterization of IM in healthy and T1DM individuals.

Chia Flour (Salvia hispanica L.) Intake Does Not Affect Weight Loss and Lipid Profile but Improve Systolic Blood Pressure Control in Obesity.

BACKGROUND: Obesity is an epidemic, multifactorial and difficult-to-control disease, besides being a risk factor for cardiovascular diseases. Among the multiple intervention proposals, the addition of chia in meals has been considered due to its composition and possible effects on weight loss and cardiovascular parameters. OBJECTIVE: We evaluate the influence of chia flour (Salvia hispanica L.) intake on body weight, body composition, energy expenditure (EE) and cardiovascular risk in obese women. METHODS: This study is a clinical trial performed with 20 adult women with obesity randomized into experimental (chia flour) and control (placebo) groups. We assessed anthropometric and biochemical measurements, as well as clinical, dietary and EE variables before intervention and 90 days later. RESULTS: There were no differences in anthropometric indicators, body composition or EE between groups, but a decrease in HDL-c (p = 0.049) and a trend towards the reduction of systolic blood pressure (SBP) (p = 0.062) was observed in the experimental group. CONCLUSION: Chia flour had a possible positive effect on SBP control, but negatively affected the lipid profile and did not seem to influence obesity control.

A Pilot Study of Dietetic, Phenotypic, and Genotypic Features Influencing Hypertensive Disorders of Pregnancy in Women with Pregestational Diabetes Mellitus.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and perinatal morbimortality. Dietetic, phenotypic, and genotypic factors influencing HDP were analyzed during a nutrigenetic trial in Rio de Janeiro, Brazil (2016-2020). Pregnant women with pregestational diabetes mellitus (n = 70) were randomly assigned to a traditional or DASH diet group. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured during prenatal visits and HDP were diagnosed using international criteria. Phenotypic data were obtained from medical records and personal interviews. Genotyping for FTO and ADRB2 polymorphisms used RT-PCR. Linear mixed-effect models and time-to-event analyses were performed. The variables with significant effect on the risk for progression to HDP were: black skin color (adjusted hazard ratio [aHR] 8.63, p = 0.01), preeclampsia in previous pregnancy (aHR 11.66, p < 0.01), SBP ≥ 114 mmHg in the third trimester (aHR 5.56, p 0.04), DBP ≥ 70 mmHg in the first trimester (aHR 70.15, p = 0.03), mean blood pressure > 100 mmHg (aHR 18.42, p = 0.03), and HbA1c ≥ 6.41% in the third trimester (aHR 4.76, p = 0.03). Dietetic and genotypic features had no significant effect on the outcome, although there was limited statistical power to test both.

Impact of Carbohydrate Counting Method during Pregnancy in Women with Pregestational Diabetes Mellitus: A Controlled Clinical Trial.

OBJECTIVE: To evaluate the effect of the carbohydrate counting method (CCM) on glycemic control, maternal, and perinatal outcomes of pregnant women with pregestational diabetes mellitus (DM). METHODS: Nonrandomized controlled clinical trial performed with 89 pregnant women who had pregestational DM and received prenatal care in a public hospital in Rio de Janeiro, state of Rio de Janeiro, Brazil, between 2009 and 2014, subdivided into historic control group and intervention group, not simultaneous. The intervention group (n = 51) received nutritional guidance from the carbohydrate counting method (CCM), and the historical control group (n = 38), was guided by the traditional method (TM). The Mann-Whitney test or the Wilcoxon test were used to compare intra- and intergroup outcomes and analysis of variance (ANOVA) for repeated measures, corrected by the Bonferroni post-hoc test, was used to assess postprandial blood glucose. RESULTS: Only the CCM group showed a reduction in fasting blood glucose. Postprandial blood glucose decreased in the 2nd (p = 0.00) and 3rd (p = 0.00) gestational trimester in the CCM group, while in the TM group the reduction occurred only in the 2nd trimester (p = 0.015). For perinatal outcomes and hypertensive disorders of pregnancy, there were no differences between groups. Cesarean delivery was performed in 82% of the pregnant women and was associated with hypertensive disorders (gestational hypertension or pre-eclampsia; p = 0.047). CONCLUSION: Both methods of nutritional guidance contributed to the reduction of postprandial glycemia of women and no differences were observed for maternal and perinatal outcomes. However, CCM had a better effect on postprandial glycemia and only this method contributed to reducing fasting blood glucose throughout the intervention. REBEC CLINICAL TRIALS DATABASE: The present study was registered in the ReBEC Clinical Trials Database (Registro Brasileiro de Ensaios Clínicos, number RBR-524z9n).

OBJETIVO: Avaliar o efeito do método de contagem de carboidratos no controle glicêmico, desfechos maternos e perinatais de gestantes com diabetes mellitus (DM) pré-gestacional. MéTODOS: Ensaio clínico controlado não randomizado realizado com 89 gestantes com DM pré-gestacional atendidas em hospital público do Rio de Janeiro, RJ, Brasil, entre 2009 e 2014, divididas em grupo controle histórico e grupo intervenção. O grupo intervenção (n = 51) recebeu orientação nutricional com base no método de contagem de carboidratos (CCM) e o grupo controle histórico (n = 38) foi orientado pelo método tradicional (MT). Os testes de Mann-Whitney ou de Wilcoxon foram usados para comparar os desfechos intra- e intergrupos e, para avaliar a glicemia pós-prandial, análise de variância (ANOVA, na sigla em inglês) para medidas repetidas foi usada. RESULTADOS: Somente o grupo com método CCM apresentou redução da glicemia de jejum. A glicemia pós-prandial diminuiu no 2° (p = 0,00) e 3° (p = 0,00) trimestres gestacionais no grupo com método CCM, e no grupo com método tradicional, a redução ocorreu apenas no 2° trimestre (p = 0,015). Para os resultados perinatais e distúrbios hipertensivos da gravidez, não houve diferenças entre os grupos. O parto cirúrgico foi realizado em 82% das gestantes e esteve associado a distúrbios hipertensivos gestacionais (p = 0,047). CONCLUSãO: Ambos os métodos de orientação nutricional contribuíram para a redução da glicemia pós-prandial e não foram observadas diferenças para os resultados maternos e perinatais. No entanto, o método CCM apresentou melhor efeito sobre a glicemia pós-prandial e foi o único que induziu redução da glicemia de jejum.

FTO and ADRB2 Genetic Polymorphisms Are Risk Factors for Earlier Excessive Gestational Weight Gain in Pregnant Women with Pregestational Diabetes Mellitus: Results of a Randomized Nutrigenetic Trial.

Excessive gestational weight gain (GWG) is associated with increased risk of maternal and neonatal complications. We investigated obesity-related polymorphisms in the FTO gene (rs9939609, rs17817449) and ADRB2 (rs1042713, rs1042714) as candidate risk factors concerning excessive GWG in pregnant women with pregestational diabetes. This nutrigenetic trial, conducted in Brazil, randomly assigned 70 pregnant women to one of the groups: traditional diet (n = 41) or DASH diet (n = 29). Excessive GWG was the total weight gain above the upper limit of the recommendation, according to the Institute of Medicine guidelines. Genotyping was performed using real-time PCR. Time-to-event analysis was performed to investigate risk factors for progression to excessive GWG. Regardless the type of diet, AT carriers of rs9939609 (FTO) and AA carriers of rs1042713 (ADRB2) had higher risk of earlier exceeding GWG compared to TT (aHR 2.44; CI 95% 1.03-5.78; p = 0.04) and GG (aHR 3.91; CI 95% 1.12-13.70; p = 0.03) genotypes, respectively, as the AG carriers for FTO haplotype rs9939609:rs17817449 compared to TT carriers (aHR 1.79; CI 95% 1.04-3.06; p = 0.02).

Modulation of the gut microbiota by probiotics and symbiotics is associated with changes in serum metabolite profile related to a decrease in inflammation and overall benefits to metabolic health: a double-blind randomized controlled clinical trial in women with obesity.

Modulation of the gut microbiota may help in treating obesity by improving host metabolic health. We aimed to evaluate the effects of probiotics or symbiotics on body weight and serum metabolite profile in women with obesity. A double-blind, parallel, randomized, controlled clinical trial was conducted with 32 adult women with body mass index ranging from 30 to 34.9 kg m-2. Volunteers followed a low-energy diet and were subjected to 8 weeks intervention: probiotic group (PG - Bifidobacterium lactis UBBLa-70, n = 10), symbiotic group (SG - Bifidobacterium lactis UBBLa-70 and fructooligosaccharide, n = 11), or control group (CG - placebo, n = 11). Analyses of anthropometric variables, gut microbiota and serum metabolites by 1H nuclear magnetic resonance (NMR) were performed at baseline and after the intervention. Multivariate statistics showed that all groups presented a decrease in glycerol and increase in arginine, glutamine and 2-oxoisovalerate. Therefore, a low-energy diet per se promoted changes in the metabolite profile related to decreased inflammation and positive effects on body weight. SG presented unique changes in metabolites (increase in pyruvate and alanine and decrease in citrate and BCAA). Negative correlations between arginine and glutamine with fat mass were observed in the SG. PG presented a decrease in 1H NMR lipid signals and negative correlation between Verrucomicrobia and Firmicutes with (CH2)n lipids. Both probiotics and symbiotics promoted changes in metabolites related to improved metabolic health. Specific metabolite changes following symbiotic intervention might suggest some advantage in providing Bifidobacterium lactis in combination with fructooligosaccharide in a low-energy diet, rather than probiotics or diet alone. Clinical trial: NCT02505854.

Profile of polyphenol intake by women with different classes of obesity: Consumption of these compounds does not reflect healthy eating.

OBJECTIVES: The aim of this study was to evaluate polyphenol intake in women with different classes of obesity and identify which are consumed more frequently and what the food sources are. METHODS: A cross-sectional study was conducted with 114 women with obesity. The study evaluated polyphenol intake via a 3-d food record using Phenol-Explorer. Anthropometric, biochemical, and dietetic variables were evaluated. RESULTS: The women's habitual food intake was low calorie and adequate in macronutrients. Mean polyphenol intake by the group was 573 ± 490, 614 ± 475, and 379 ± 25 mg/d for class I, class II, and class III obesity (P = 0.002), respectively. The most frequent food or beverage consumed by the group was coffee and caffeoylquinic acid, its phenolic compound. Fruits, vegetables, and nuts contributed the least to the intake of polyphenols. CONCLUSIONS: Although the diets of the study participants did include some food sources of polyphenols, they were not of sufficient quality to significantly contribute to a healthy diet; instead, they sometimes were foods may have that contributed to weight gain. Women with class III obesity consumed the most calories; however, they had low fruit, vegetable, and whole foods intake.

Hypocaloric diet with lower meal frequency did not affect weight loss, body composition and insulin responsiveness, but improved lipid profile: a randomized clinical trial.

Dietary approaches are essential to control obesity, but the effectiveness of changes in meal frequency (MF) as a strategy for body weight loss or maintenance remain unclear. This study aimed to evaluate the influence of MF of a hypocaloric diet on weight loss, body composition, active ghrelin levels and metabolic indicators of obese women. This is a randomized, parallel clinical trial, including 40 women divided into two groups that received a hypocaloric diet with different MFs: MF6: six meals per day, and MF3: three meals per day. Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of the intervention. Dietary consumption did not differ between groups, before or after intervention. The two groups reduced their energy intake after intervention, but there were no differences between the groups. Waist circumference (WC) was reduced and resting metabolic rate had increased in the MF3 group at the end compared to baseline. Moreover, there was a significant difference in the triglyceride levels between groups after intervention, with an important reduction in the MF3 group, although changes in body composition, blood glucose, plasma ghrelin levels and EE variables did not differ between the groups at the end. It is concluded that, the hypocaloric diet with different MF each day did not change weight loss, body composition or insulin responsiveness, but there was an improvement of triglyceridemia in the MF3 group. The present study suggests that eating snacks between meals is not an important factor for weight loss and improvement of metabolic health in women with obesity.

Metabolic and Appetite Effects of Fructose and Glucose in Subjects with Type 1 Diabetes: A Randomized Crossover Clinical Trial.

BACKGROUND: Fructose has been widely used for producing lower post-infusion glucose increase than other carbohydrates, but it seems that it promotes an increase in post-infusion triglycerides. OBJECTIVE: The present study investigated the effects of fructose and glucose in metabolic variables and appetite sensations in patients with type 1 diabetes mellitus (T1DM). METHODS: This is a single-blind, randomized, and crossover study (washout of 1-5 weeks), which evaluated 16 adult T1DM patients, accompanied at University Hospital. After eight hours of overnight fasting, there was an assessment of capillary blood glucose, anthropometric variables, appetite sensations, and laboratory tests (glycemia, lipemia, leptin and glucagon) were conducted. Subsequently, they received 200mL of solutions with water and 75g of crystal fructose or glucose. Appetite sensations and capillary blood glucose were evaluated in different post-infusion times. Blood was drawn after 180 minutes for the laboratory tests. RESULTS: Blood glucose increased after the intake of both solutions, but glucose induced a higher elevation. None of them increased triglycerides or glucagon. Glucagon maintenance was similar among the solutions. Furthermore, both solutions reduced leptin and increased fullness, but only fructose increased the lack of interest in eating sweets. CONCLUSION: Fructose induced a smaller increase in postprandial blood glucose than glucose, without changes in triglycerides and glucagon. In addition, leptin levels and appetite sensations were similar to glucose. Other studies are needed in order to confirm these findings, especially in the long term, so that their use becomes really reliable.

A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil. MATERIAL AND METHODS: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values. RESULTS: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome. CONCLUSION: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.

Profile of the gut microbiota of adults with obesity: a systematic review.

Recently, relationship between gut microbiota composition and development of obesity has been pointed. However, the gut microbiota composition of individual with obesity is not known yet. Therefore, this systematic review aimed to evaluate differences in profile of gut microbiota between individuals with obesity and individuals with normal weight. A search performed on August 2019 in the databases Pubmed, Scopus, Web of Science, Cochrane library, Lilacs and gray literature using the terms: "microbiota", "microbiome", "obesity", "obesity morbid", and "humans". Studies assessing the gut microbiota composition in adults with obesity and lean were included. Quality assessment was performed by Newcastle-Ottawa Quality Assessment Scale. Of the 12,496 studies, 32 were eligible and included in this review. Individuals with obesity have a greater Firmicutes/Bacteroidetes ratio, Firmicutes, Fusobacteria, Proteobacteria, Mollicutes, Lactobacillus (reuteri), and less Verrucomicrobia (Akkermansia muciniphila), Faecalibacterium (prausnitzii), Bacteroidetes, Methanobrevibacter smithii, Lactobacillus plantarum and paracasei. In addition, some bacteria had positive correlation and others negative correlation with obesity. Individuals with obesity showed profile of gut microbiota different than individual lean. These results may help in advances of the diagnosis and treatment of obesity.

The prevalence and risk factors for sarcopenia in older adults and long-living older adults.

PURPOSE: Sarcopenia is a muscular syndrome that is related to several adverse risks. The present study aimed to evaluate the prevalence of risk of sarcopenia and associated factors in older adults and long-living older adults. METHODS: A crosssectional epidemiological study of older adults patients at a geriatric outpatient clinic. The older adults were evaluated for sarcopenia risk using the SARC-F questionnaire supplemented with the measurement of the calf circumference. In addition, nutritional status was characterized using the Mini Nutritional Assessment, and the relationship of sarcopenia with associated factors (comorbidities, polypharmacy, smoking). RESULTS: A total of 100 eligible older adults with a mean age of 77.2 ±â€¯1.8 years in the older adults and 86.3 ±â€¯4.2 years in the long-living older adults (p < 0.001) were evaluated. The long-living older adults (OR = 6.1; 95 % CI: 1.44-16.09; p = 0.01) and older adults at risk of malnutrition (OR = 13.6; 95 % CI: 1.55-11.38; p < 0.05) had a higher risk of sarcopenia, whereas BMI ≥ 27 kg/m 2 (OR = 0; 95 % CI: 0-0.06; p < 0.001) was a protective factor. The risk of sarcopenia was six times higher in the over-80 s (95 % CI = 1.44, 16.09), while the older adults with malnutrition or at nutritional risk ran a 13 times higher risk of sarcopenia (95 % CI = 1.55, 11.38). CONCLUSION: The prevalence of risk of sarcopenia was higher in the long-living older adults and the older adults at nutritional risk, making its early evaluation in clinical practice important.

Effect of coconut oil on weight loss and metabolic parameters in men with obesity: a randomized controlled clinical trial.

Coconut oil appears to help in weight loss and improve metabolic parameters associated with obesity. We evaluate the influence of coconut oil on the body composition, lipid profile and glycemia in men with obesity. A controlled, randomized clinical trial was performed with 29 adult men affected by obesity. They were randomized between two groups receiving a daily intake of 1 tablespoon (12 mL) of extra virgin coconut oil (CO, n = 15) or soybean oil (SO, n = 14), and an isoenergetic balanced diet. The anthropometric profile, lipid profile and glycaemia were evaluated at the baseline and 45 days after intervention. The Mann-Whitney test was performed to compare the groups, and the Wilcoxon test was performed to compare the times. We considered a value of p < 0.05 as significant. There was no difference in anthropometric variables between the groups before and after intervention. The level of HDL cholesterol increased (3.67 ± 8.08 versus-3.79 ± 10.98, p = 0.02) and the TC/HDL cholesterol ratio decreased (-0.63 ± 0.82 versus 0.23 ± 0.80, p = 0.03) in the CO group, compared to the SO group. Coconut oil included in the isoenergetic balanced diet could increase HDL cholesterol and decrease the TC/HDL cholesterol ratio in men with obesity.

Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity.

BACKGROUND: The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity. METHODS: This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0-11 years), 19 patients in the adolescence/youth-onset group (12-21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject's DNA was assessed using automated Sanger sequencing. RESULTS: Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity. CONCLUSION: This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.

Postprandial metabolic effects of fructose and glucose in type 1 diabetes patients: a pilot randomized crossover clinical trial.

OBJECTIVE: To test the influence of oral fructose and glucose dose-response solutions in blood glucose (BG), glucagon, triglycerides, uricaemia, and malondialdehyde in postprandial states in type 1 diabetes mellitus (T1DM) patients. SUBJECTS AND METHODS: The study had a simple-blind, randomized, two-way crossover design in which T1DM patients were selected to receive fructose and glucose solutions (75g of sugars dissolved in 200 mL of mineral-water) in two separate study days, with 2-7 weeks washout period. In each day, blood samples were drawn after 8h fasting and at 180 min postprandial to obtain glucose, glucagon, triglycerides, uric acid, lactate, and malondialdehyde levels. RESULTS: Sixteen T1DM patients (seven men) were evaluated, with a mean age of 25.19 ± 8.8 years, a mean duration of disease of 14.88 ± 4.73 years, and glycated hemoglobin of 8.13 ± 1.84%. Fructose resulted in lower postprandial BG levels than glucose (4.4 ± 5.5 mmol/L; and 12.9 ± 4.1 mmol/L, respectively; p < 0.01). Uric acid levels increased after fructose (26.1 ± 49.9 µmol/L; p < 0.01) and reduced after glucose (-13.6 ± 9.5 µmol/L; p < 0.01). The malondialdehyde increased after fructose (1.4 ± 1.6 µmol/L; p < 0.01) and did not change after glucose solution (-0.2 ± 1.6 µmol/L; p = 0.40). Other variables did not change. CONCLUSIONS: Fructose and glucose had similar sweetness, flavor and aftertaste characteristics and did not change triglycerides, lactate or glucagon levels. Although fructose resulted in lower postprandial BG than glucose, it increased uric acid and malondialdehyde levels in T1DM patients. Therefore it should be used with caution. ClinicalTrials.gov registration: NCT01713023.