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Ana Carolina Proença da Fonseca,1,2 Gabriella de Medeiros Abreu,2 Lohanna Palhinha,1 Verônica Marques Zembrzuski,2 Mario Campos Junior,2 João Regis Ivar Carneiro,3 José Firmino Nogueira Neto,4 Fernanda Cristina C Mattos Magno,5 Eliane Lopes Rosado,5 Clarissa Menezes Maya-Monteiro,1 Giselda Maria Kalil de Cabello,2 Pedro Hernán Cabello,2,6 Patricia Torres Bozza1 1Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 3Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 5Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilCorrespondence: Ana Carolina Proença da FonsecaHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 4365 Brasil Avenue, Leônidas Deane Building – Office 611/615, Rio de Janeiro, RJ 21040-360, BrazilTel +552138658192Fax +552138658239Email ana.proenca@ioc.fiocruz.brBackground: 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.Keywords: BDNF, severe obesity, rare mutation, early-onset obesity, metabolic syndrome

Ana Carolina Proença da Fonseca,1 Gabriella Medeiros Abreu,1 Verônica Marques Zembrzuski,1 Mario Campos Junior,1 João Regis Ivar Carneiro,2 José Firmino Nogueira Neto,3 Giselda Maria Kalil Cabello,1 Pedro Hernán Cabello1,41Human Genetics Laboratory, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, Brazil; 2Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 4Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilBackground: Obesity occurs due to the interaction between the genetic background and environmental factors, including an increased food intake and a sedentary lifestyle. Nowadays, it is clear that there is a specific circuit, called leptin-melanocortin pathway, which stimulates and suppresses food intake and energy expenditure. Therefore, the aim of this study was to evaluate the influence of genetic variants related to appetite regulation and energy expenditure on severe obesity susceptibility and metabolic phenotypes in a Brazilian cohort.Material and methods: A total of 490 participants were selected (298 severely obese subjects and 192 normal-weight individuals). Genomic DNA was extracted and polymorphisms in protein related to agouti (AGRP; rs5030980), ghrelin (GHRL; rs696217), neuropeptide Y (NPY; rs535870237), melanocortin 4 receptor (MC4R; rs17782313), brain-derived neurotrophic factor (BDNF; rs4074134) and fat mass and obesity-associated (FTO; rs9939609) genes were genotyped using TaqMan® probes. Demographic, anthropometric, biochemical and blood pressure parameters were obtained from the participants.Results: Our results showed that FTO rs9939609 was associated with severe obesity susceptibility. This polymorphism was also related to body weight, body mass index (BMI), waist to weight ratio (WWR) and inverted BMI. Individuals carrying the mutant allele (A) showed higher levels of BMI as well as lower values of WWR and inverted BMI.Conclusion: This study showed that FTO rs9939609 polymorphism plays a significant role in predisposing severe obesity in a Brazilian population.Keywords: leptin-melanocortin pathway, FTO, obesity, polymorphisms, hypothalamus

Ana Carolina Proença da Fonseca,1 Gabriella de Medeiros Abreu,1 Verônica Marques Zembrzuski,1 Mario Campos Junior,1 João Regis Ivar Carneiro,2 Fernanda Cristina C Mattos Magno,3 Eliane Lopes Rosado,3 José Firmino Nogueira Neto,4 Giselda Maria Kalil de Cabello,1 Pedro Hernán Cabello1,5 1Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil; 2Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 3Institute of Nutrition Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 5Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, Brazil Background: Melanocortin 4 receptor gene (MC4R) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype–genotype correlation within MC4R variant carriers. Methods: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0–11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12–21 years). The entire coding region of MC4R gene was screened by Sanger sequencing. Results: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R. It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist–hip ratio when compared to noncarriers (P=0.048). These missense variants were also associated with hypertension (P=0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers (P=0.020 and P=0.065, respectively). Val103Ile was also associated with hypertension (P=0.003). Conclusion: This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure. Keywords: MC4R, severe obesity, mutation, start lost, blood pressure

Introduction: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications., Methods: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m 2 ) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m 2 ). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan ® assays., Results: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms., Discussion/conclusion: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 da Fonseca, Assis, Salum, Palhinha, Abreu, Zembrzuski, Campos Junior, Nogueira-Neto, Cambraia, Souza Junior, Maya-Monteiro, Cabello, Bozza and Carneiro.)

The objective of this study was to evaluate the impact of fasting easing on laboratory measurements of the lipid profile, in order to contribute to the fidelity of interpretation of laboratory results. Starting in October 2022, a Systematic Literature Review (SRL) was carried out, using articles indexed in the electronic databases PubMed/MEDLINE, EMBASE, Scopus, LILACS and Cochrane Library, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes Group (PRISMA). This RSL was registered with PROSPERO, under registration number CRD42022370007. For inclusion, articles had to be original and developed in humans. After evaluating the methodological quality and analyzing the risk of bias, we obtained 16 articles published between 1994 and 2021, providing data on a total of 398,709 individuals, aged between 3 and 93 years. According to the selected studies, lipid profile measurements performed with flexible fasting, in addition to bringing benefits to patients and the pre-analytical system of the clinical laboratory, are more suitable for determining cardiovascular risk, mainly through the assessment of values obtained in the determination of triglycerides. It is therefore concluded that the optional use of fasting must be established through medical advice. In addition, laboratory methods and readings must be readjusted to this reality, informing through the report the parameters related to the lipid profile with and without the use of a 12-hour fast., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: It is known that consuming a high-fat meal (HFM) induces microvascular dysfunction (MD) in eutrophic women and aggravates it in those with obesity. Our purpose was to investigate if the MD observed after a single HFM intake is caused by endothelial damage or increased inflammatory state, both determined by blood biomarkers., Methods: Nineteen women with obesity (BMI 30-34.9 kg/m 2 ) and 18 eutrophic ones (BMI 20.0-24.9 kg/m 2 ) were enrolled into two groups: Obese (OBG) and Control (CG), respectively. Blood samples were collected at five-time points: before (fasting state) and 30, 60, 120, and 180 min after HFM intake to determine levels of adipokines (adiponectin, leptin), non-esterified fatty acid (NEFA), inflammatory [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)] and endothelium damage [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1)] biomarkers., Results: Levels of soluble E-selectin, leptin, and PAI-1 were higher in OBG at all-time points (P < 0.05) compared to CG. In the fasting state, OBG had higher levels of NEFA compared to CG (P < 0.05). In intra-group analysis, no significant change in the levels of circulating inflammatory and endothelial injury biomarkers was observed after HFM intake, independently of the group., Conclusion: Our findings suggest that women with obesity have an increased pro-inflammatory state and more significant endothelial injury compared to eutrophic ones. However, the consumption of a HFM was not sufficient to change circulating levels of inflammatory and endothelial injury biomarkers in either group., Registration Number for Clinical Trials: NCT01692327., (© 2022. The Author(s).)

Visceral adipose tissue (VAT) is associated with various metabolic disorders, and adipokines, secreted by adipose tissue, are involved in their pathogenesis. This study investigated associations between VAT/subcutaneous adipose tissue (SAT) ratio, inflammatory markers, and cardiovascular (CV) risk-score in adults. Plasma levels of adipokines, plasma lipid profile, blood pressure, and body composition (using dual-emission x-ray absorptiometry) were determined. CV risk-score based on the American College of Cardiology and the American Heart Association (ACC/AHA) score was calculated in a sample of 309 Brazilian civil servants aged <60 years. Participants' VAT/SAT ratio were categorized into quartiles. Among males, plasma leptin (2.8 ng/mL) and C reactive protein (CRP) (0.2 mg/dL) (P<0.05) levels were higher at P75 and P50 than P5, and the highest calculated CV risk-score was observed at P75 (7.1%). Among females, higher plasma adiponectin levels were observed at P25 (54.3 ng/mL) compared with P75 (36 ng/mL) (P<0.05). Higher plasma CRP levels were observed at P75 (0.4 mg/dL) compared with P5 (0.1 mg/dL) (P<0.05). Higher CV risk-score was observed at P75 (2.0%) compared with P5 (0.7%). In both sexes, VAT and VAT/SAT ratio were directly associated with plasma leptin, CRP, and CV risk-score, and inversely associated with adiponectin; SAT was directly associated with plasma leptin and CRP (P<0.01); interleukin (IL)-10 and CRP were directly associated with adiponectin and leptin, respectively (P<0.05). Among men only, IL-10 (inversely) and CRP (directly) were associated with CV risk-score (P=0.02). Our results strengthened the relevance of the VAT/SAT ratio in cardiovascular risk.

Background: Vitamin A deficiency (VAD) and anemia are the most prevalent nutritional deficiency in children globally. The dried blood spot (DBS) method has been used in prevalence studies of VAD and anemia in different age groups. However, it has not yet been validated for children., Objectives: This study aimed to assess the reproducibility and validity of DBS in the diagnosis of VAD and anemia in preschoolers., Methods: Venous and capillary blood samples were collected from a representative sample of children <5 y old who attended the public health system in Rio de Janeiro. Serum retinol and hemoglobin were measured in 235 and 182 children, respectively. Serum retinol was measured with HPLC and hemoglobin was measured with spectrophotometry in samples of venous (gold standard) and capillary blood (test method, DBS). DBS reproducibility was assessed with the intraclass correlation coefficient (ICC), κ, and prevalence-adjusted and bias-adjusted κ (PABAK). DBS validity was assessed with sensitivity, specificity, accuracy index (AI), positive predictive value (PPV), and negative predictive value (NPV)., Results: DBS showed very good reproducibility for serum retinol (ICC = 0.94, κ = 0.83, PABAK = 0.76) and very good/good reproducibility for hemoglobin (ICC = 0.86, κ = 0.69, PABAK = 0.69). Prevalence rates for VAD by the reference and test methods were 11.5% and 11.9%, respectively, whereas the anemia rates were 19.2% and 46.2%. The test method showed low sensitivity (33%) and PPV (32%) and high specificity (91%) and NPV (92%) for serum retinol. For hemoglobin, the test method showed fair sensitivity (71%), low PPV (30%), fair specificity (60%), and high NPV (90%). AI was 83% for VAD and 62% for anemia., Conclusions: The results suggest that DBS is adequate for the diagnosis of VAD in preschool children, but not for anemia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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/m 2 ) 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&#95;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.

Background: Bariatric surgery induces weight loss, but changes in glucose metabolism, gut peptides, and inflammatory biomarkers still have conflicting results., Settings: University hospital., Objectives: We investigated glucose metabolism, gut hormones, and inflammatory profile after bariatric surgery and medical treatment., Methods: Forty patients with obesity were recruited and were subjected to Roux-en-Y gastric bypass (n = 15; Bariatric Surgery Group - BSG) or received medical care (n = 20; MG). Sleeve gastrectomy was performed in five patients who were excluded from analysis. Glucose, insulin, homeostatic model for the assessment of insulin resistance (HOMA-IR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon, ghrelin, dipeptidyl peptidase-4 (DPP-4) activity, circulating lipopolysaccharide (LPS), LPS-binding protein (LPB) and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and three months after each treatment. Except for HOMA-IR, hs-CRP, and LBP, all variables were assessed at fasting and 30- and 60-minutes after a standard meal., Results: After 3 months, both groups lost weight. However, BSG had a more extensive reduction than MG (respectively, 17.6% vs. 4.25%; P < 0.01). Except for LPS levels, higher on BSG than MG (1.38 ± 0.96 vs. 0.83 ± 0.60 EU/ml, P < 0.01), groups were similar before treatment. In respect to metabolic/hormonal changes, the BSG showed higher glucose, insulin, GLP-1, and GIP levels at 30-min and also GLP-1 at 30- and 60-minutes. DPP-4 activity, HOMA-IR, and fasting LBP did not change. LPS levels at 60-minutes decreased after surgery in the BSG. hs-CRP decreased on BSG compared to MG., Conclusions: Bariatric surgery resulted in more extensive effects on glucose metabolism, gut hormones, and inflammation., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

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/m 2 , 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Salum, de Souza, Abreu, Campos Junior, Kohlrausch, Carneiro, Nogueira Neto, Magno, Rosado, Palhinha, Maya-Monteiro, Cabello, Cabello, Bozza, Zembrzuski and da Fonseca.)

Background: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides., Subjects/methods: We included 38 drug-naïve patients, all women aged between 19 and 50 years, with BMI ≥ 30 kg/m 2 . We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points., Results: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged., Conclusions: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation.

Objective: To evaluate the effects of a hypoenergetic diet (HD)associated with açaí pulp consumption on oxidative stress, antioxidant status and inflammatory biomarkers in overweight, dyslipidemic individuals., Research Methods & Procedures: A randomized, double-blind, placebo-controlled clinical trial was conducted for 90 days. The study began with a 30-day run-in period, during which the intervention was exclusively a HD. Following this period, volunteers were randomized into 2 groups, and 200 g of either açaí pulp or placebo were added to the HD for 60 days. Anthropometric measurements, arterial pressure, oxidative stress and antioxidant status biomarkers, inflammatory and biochemical biomarkers were evaluated., Results: Sixty-nine volunteers completed the clinical trial, 30 of which were in the HD + açaí group and 39 in HD + placebo group. Plasma 8-isoprostane concentrations significantly reduced 60 days after the intervention in the açaí group (p = 0.000), and there was a significant difference between the groups (açaí versus placebo; p = 0.037). Regarding inflammatory status parameters, a significant reduction in IL-6 was observed in the HD + açaí group (p = 0.042), and IFN-γ decreased significantly in both groups, HD + açaí (p = 0.001) and HD + placebo (p = 0.008); there were, however, no differences between the groups. Lipid profile parameters and blood glucose levels did not show change, regardless of nutritional intervention., Conclusion: The addition of açaí to a HD, for 60 days, reduced oxidative stress and improved inflammation in overweight, dyslipidemic individuals., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Obesity is a major public health problem worldwide. It has a complex etiology, influenced by environmental and genetic factors. FTO has been recognized as an important genetic factor for obesity development. This study evaluated the contribution of FTO polymorphisms (rs9939609 and rs17817449) for extreme obesity in terms of the period of obesity onset, anthropometric, and biochemical parameters. The haplotype and the combined effects of FTO risk alleles on obesity susceptibility were evaluated. We investigated 169 normal-weight subjects (body mass index, BMI: 22.8 [21.0; 24.0] kg/m2) and 123 extremely obese individuals (BMI: 47.6 [44.1; 53.1] kg/m2). Genotyping was performed by real time PCR. Our results showed a strong association between FTO variants and extreme obesity. Carriers of the AT haplotype had an increased risk for extreme obesity. Gene scores suggested that the risk of developing extreme obesity was increased 1.37-fold per risk allele added. Both polymorphisms also influenced BMI and body weight. Additionally, rs17817449 influenced triglyceride levels. No effect of FTO variants on the period of obesity onset was found. In conclusion, the FTO polymorphisms showed a strong association with development of extreme phenotype of obesity and adiposity modulation in a Brazilian population.

Portable haemoglobinometers have been used in order to estimate the prevalence of anaemia in diverse settings. However, few studies have been conducted to evaluate their performance in children of different age groups in distinct epidemiological contexts. To evaluate the reproducibility and reliability of a portable haemoglobinometer for the diagnosis of anaemia in children <5 years Hb was measured in the venous blood of 351 children <5 years by an automated system (standard method) and in three capillary blood samples, using a portable haemoglobinometer (HemoCue ® ; test method). The reproducibility of the device and of the test method was evaluated using the intraclass correlation coefficient (ICC) (Hb in its continuous form), κ and prevalence-adjusted bias-adjusted κ (PABAK) (categorised variable: anaemia: yes/no). For test method validation, Bland-Altman analyses were performed and sensitivity, specificity, accuracy rate, positive predictive value (PPV) and negative predictive values (NPV) were calculated. The haemoglobinometer presented good device reproducibility (ICC = 0·79) and reasonable method reproducibility (puncture, collection and reading) (ICC = 0·71). Superficial and fair agreement (κ) and good agreement (PABAK) were observed among the diagnoses obtained through the test method. The prevalence of anaemia was 19·1 and 19·7 % using the standard and the test method, respectively, with no statistically significant differences. The test method presented higher specificity (87·7 %) and NPV (88·3 %) than sensitivity (50·7 %) and PPV (49·3 %), and intermediary accuracy rate (57·8 %). HemoCue ® showed good device reproducibility and reasonable method reproducibility, as well as good performance in estimating the prevalence of anaemia. Nevertheless, it showed a fair reliability and low individual diagnostic accuracy., (© The Author(s) 2020.)

Introduction: Cervical cancer screening is an important tool in public health. Liquid-based cytology (LBC) has been performed at the studied hospital for 7 years. The present study compares the performance of 2 LBC techniques with conventional cytology., Objective: Our objective is to verify the sensitivity for the detection of neoplastic and preneoplastic epithelial atypia, as well as the positive predictive value of the 3 methodologies., Methods: We analyzed retrospectively 24,529 cases and evaluated the conventional cytology, ThinPrep®, and BD SurePath® performance categorizing the results according to the Bethesda system. We also compared the level of unsatisfactory samples, the presence of elements from the squamocolumnar junction, and the detection of pathogenic microorganisms., Results: ThinPrep® (1.43%) showed superior sensitivity over BD SurePath® (0.91%) and conventional cytology (0.71%) in terms of the detection of high-grade lesions; however, in terms of squamous atypia as a whole (ASC-US+), BD SurePath® (6.44%) proved to be more sensitive than conventional cytology (5.28%) and ThinPrep® (3.73%)., Conclusions: The results show the advantage of implementing LBC in routine screening for cervical lesions. In this study, BD SurePath® achieved the overall best performance considering the studied variables., (© 2020 S. Karger AG, Basel.)

Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure., Objectives: The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5-52.2]) and 191 normal-weight subjects (BMI 22.8 [21.1-23.9])., Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A(rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman® assay. For the FNDC5 gene, screening of exons 3-5 as well as their intron-exon boundaries was performed using automatic sequencing., Results: Our results demonstrated that PPARGC1Ars2970847 and UCP1rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation., Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Obesity is the main risk factor for diabetes and excessive visceral fat triggers low-grade inflammatory process, mediated by activation and release of cytokines and high flow of free fatty acids that contribute to insulin resistance, increased oxidative stress, and impaired endothelial function. Metformin and vildagliptin have known vasculoprotective actions, but the value of these drugs on drug-naïve diabetic patients during 30 days use warrants investigation. Our purpose was to observe their effects on endothelial function, oxidative stress, inflammatory biomarkers, and plasma viscosity., Methods: 38 women with obesity and type 2 diabetes drug-naïve, aged between 19 and 50 years, BMI ≥ 30 kg/m 2 , were recruited and subjected to measurements of endothelial function, nutritive skin microvascular reactivity, plasma viscosity, inflammatory and oxidative stress biomarkers at baseline and randomized 1:1 to ingest metformin (850 mg twice/day) or vildagliptin (50 mg twice/day) during 30 days, and then, re-evaluated., Results: No differences between groups were noticed at baseline. After treatment, vildagliptin promoted an improvement on endothelial-dependent and -independent vasodilatations, at arteriole level, while metformin resulted in improved nutritive microvascular reactivity, at the capillary level. Intragroup analysis showed that vildagliptin reduced insulin, C-peptide and oxidized LDL, and increased adiponectin and glucagon-like peptide-1 while metformin reduced weight, plasma glucose, total cholesterol, HDL-c, LDL-c, and dipeptidyl peptidase-4 activity, with an unexpected increase on tumor necrosis factor-α. No significant difference in plasma viscosity was noted., Conclusions: In the vascular beds investigated, both drugs used for only 30 days improved endothelial function, through distinct, and possibly, complementary mechanisms on drug-naïve diabetic women. Trial Registration ClinicalTrials.gov: NCT01827280., Competing Interests: Competing interestsThe authors declare that they have no competing interests. LGK-A received funds from Novartis S.A. that partially supported this study.

Background: Melanocortin 4 receptor gene ( MC4R ) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype-genotype correlation within MC4R variant carriers., Methods: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0-11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12-21 years). The entire coding region of MC4R gene was screened by Sanger sequencing., Results: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R . It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist-hip ratio when compared to noncarriers ( P =0.048). These missense variants were also associated with hypertension ( P =0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers ( P =0.020 and P =0.065, respectively). Val103Ile was also associated with hypertension ( P =0.003)., Conclusion: This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The enzyme dipeptidyl peptidase 4 (DPP4) has been recently recognized as an adipo-myokine. However, studies that associate its constitutive activity with body composition, anthropometry, and insulin resistance (IR) are very scarce and included only healthy people., Methods: First, we investigated the relationships of constitutive DPP4 activity, body composition (assessed by bioelectrical impedance analysis), and measures of adiposity and IR in fifty-two subjects of both sexes, 18-50 years, and BMI ≥25.0 kg/m 2 who comprised three groups according to glucose tolerance. Additionally, we evaluated associations among DPP4 activity and adipokines, gut peptides, and biochemical variables at fasting and 30 and 60 min after a standardized meal intake., Results: DPP4 activity was no different among the three groups. At fasting, pooled analysis showed it was positively correlated with measures of central adiposity, such as WC ( P = 0.011) and WHR ( P = 0.009), and with all measures of IR, but inversely related to indexes of general adiposity, such as fat mass percentage ( P = 0.014) and BAI ( P = 0.0003). DPP4 activity was also associated with lean mass ( r = 0.57, P < 0.0001). After meal intake, DPP4 activity remained significantly associated with insulin, leptin, and resistin. In multiple regression analysis, BAI, WHR, percent lean mass, HOMA-IR, and leptin influenced DPP4 activity and explained approximately 26% of the variance on it., Conclusions: Constitutive DPP4 activity is positively associated with lean mass, central adiposity, and IR and negatively to general adiposity. Furthermore, it seems to be influenced by body composition and IR and could also be viewed as an adipo-myokine in subjects with excessive adiposity and different stages of glucose tolerance.

Background: Frequently, ingestion of lipids exceeds our daily requirements and constantly exposes humans to circulating lipid overload which may lead to endothelial dysfunction (ED), the earliest marker of atherosclerosis. Nailfold videocapillaroscopy (NVC) technique can detect ED on microcirculation. Using NVC, we aimed to demonstrate if metabolic alterations evoked by high-fat meals can act differently on microvascular endothelial reactivity in lean and women with obesity., Methods: Women, aged between 19 and 40 years, were allocated to control group (CG) and with obesity group (OBG) and were subjected to blood analysis for determination of glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) and NVC evaluation at fasting and 30, 60, 120, and 180-min after high-fat meal ingestion. NVC technique evaluated microvascular reactivity through the following variables: red blood cell velocity (RBCV) at rest and after 1-min ischemia (maximal red blood cell velocity, RBCV max ) and time taken to reach it (TRBCV max ). A P value ≤0.05 was considered significant., Results: High-fat meal promoted a two-phase response in both groups: one until 60-min, associated with glucose and insulin levels, and the other after 120-min, associated with TG levels. Significant differences between groups were observed concerning insulin and HDL-c concentrations only at fasting and TC, TG, and LDL-c levels in all-time points. Regarding microvascular reactivity, RBCV, RBCV max , and TRBCV max were significantly different in OBG at 30-min compared to baseline. RBCV max and TRBCV max were significantly different in CG at 30-min and 60-min comparing to fasting. In all-time points, OBG presented RBCV, RBCV max  , and TRBCV max significantly different in comparison to CG., Conclusion: High-fat meal worsened ED on microcirculation in women with obesity and induced impairment of endothelial function in lean ones, reinforcing the association between high-fat meal and atherosclerosis.

Objective: In patients with diabetes, dipeptidyl peptidase 4 (DPP4) inhibition is associated with attenuation of inflammation and endothelial dysfunction. Here, we investigated the associations between constitutive DPP4 activity, inflammatory biomarkers, and microvascular reactivity in subjects with excess body weight without diabetes., Methods: Forty subjects of BMI ≥ 25.0 kg/m 2 and without diabetes were cross-sectionally evaluated. We assessed microvascular blood flow and vasomotion by laser Doppler flowmetry, and measured at baseline, 30, and 60 min after a standardized meal: DPP4 activity, glucose, insulin, hs-CRP, TNF-α, IL-6, PAI-1, ICAM-1, and VCAM-1. HOMA-IR and HOMA-AD were used to assess insulin resistance. Linear correlations of DPP4 activity with the biomarkers of inflammation and components of microvascular function were conducted. In step further, multiple regression analyses were performed to test whether some of these variables could influence, or be influenced by, the plasma DPP4 activity., Results: DPP4 activity was inversely associated with VCAM-1 at baseline (P < 0.05), and DPP4 activity AUC was inversely correlated with the myogenic component AUC of vasomotion (P < 0.05). In multiple regression analysis, HOMA-AD, IL-6, VCAM-1, PAI-1, blood flow, and vasomotion influenced DPP4 activity and explained almost 40% of the variance on it. When HOMA-AD, VCAM-1, and blood flow were placed respectively as dependent variables, DPP4 activity exerted a significant effect in all of them., Conclusions: Constitutive DPP4 activity was associated with early markers of endothelial proinflammatory activation and microvascular function, and may have an influence and even be influenced by inflammation and microvascular blood flow in subjects with excess body weight without diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Knee osteoarthritis (KOA) is one of the most frequent noncommunicable diseases with pain associated symptoms and affects the musculoskeletal system. Various forms of treatment can be indicated, and nonpharmacological treatment is also an available option for the management of KOA individuals. For instance, auriculotherapy (AT) is one possible procedure associated with the Traditional Chinese Medicine for dealing with KOA. It is believed that the concentration of certain biomarkers could be altered in individuals with KOA after AT. The aim of this study was to evaluate the effect of AT on plasma concentration of biomarkers in KOA individuals. This intervention is a controlled trial. Twenty-one subjects were grouped in two groups and submitted to AT with the stimulation of the Shen Men, kidney, and knee points in the treatment group or different points in the control group, once a week for 5 weeks. Blood was collected before the beginning of protocols and a week after the last session. Kolmogorov-Smirnov and Wilcoxon tests were performed, and a p ≤ 0.05 was considered statistically significant. Hematological parameters did not show any significant variation between the control group and treated group. Concerning the biochemical parameters, a significant reduction of direct bilirubin (from 43.31 ± 22.10 to 21.21 ± 5.30 μmol/L, p = 0.003), aspartate aminotransferase (from 0.48 ± 0.16 to 0.38 ± 0.09 μKat/L, p = 0.010), and triglycerides (from 7.04 ± 2.90 to 5.45 ± 2.57 mmol/L, p = 0.008) in the treated group was obtained. In conclusion, the analysis of results suggests that AT might be a useful intervention for the management of KOA individuals., (Copyright © 2018. Published by Elsevier B.V.)

Background: Green tea consumption has been inversely associated with cardiovascular disease (CVD) in epidemiological studies. Although some interventional trials suggest that green tea has beneficial effects on CVD risk factors, such as hypertension and obesity, others have failed to show such benefits., Aims: To evaluate the short-term effects of green tea on blood pressure, endothelial function, metabolic profile, and inflammatory activity in obese prehypertensive women., Methods: This study was a crossover, randomized, double-blind, placebo-controlled clinical trial. Participants were randomly allocated to receive daily 3 capsules containing either 500 mg of green tea extract (GTE) or a matching placebo for 4 weeks, with a washout period of 2 weeks between treatments. Each GTE capsule contained 260 mg of polyphenols. At the beginning and at the end of each treatment, participants were submitted to evaluation of blood pressure (ambulatory blood pressure monitoring, ABPM), endothelial function (Endo-PAT 2000 and cellular adhesion molecules), nutritional parameters, metabolic profile, and biomarkers of inflammation., Results: Twenty women age 41.1 ± 8.4 years completed the study. After 4 weeks of GTE supplementation in comparison with placebo, there was a significant decrease (p < 0.05) in systolic blood pressure at 24 hours (-3.61 ± 1.23 vs 1.05 ± 1.34 mmHg), daytime (-3.61 ± 1.26 vs 0.80 ± 1.57 mmHg), and nighttime (-3.94 ± 1.70 vs 1.90 ± 1.66 mmHg). Changes in diastolic blood pressure and in all other parameters did not present a significant difference between GTE and placebo., Conclusion: The findings of this study suggest that in obese prehypertensive women, short-term daily intake of GTE may decrease blood pressure.

Obesity is the most common nutritional disorder. This disease is a multifactorial disease influenced by environmental and genetic factors. This study investigated the relationship between common variants of adiponectin ( ADIPOQ ), retinoic acid receptor responder 2 ( RARRES2 ), and peroxisome proliferator-activated receptor- γ coativator-1 ( PPARGC1 ) and obesity-related traits and susceptibility. A total of 167 individuals with obesity and 165 normal-weight subjects were recruited. Genotype frequencies of rs182052 in ADIPOQ differed significantly between the groups. Genotype AA was observed at a higher frequency in case than in control subjects. Association analysis showed that the A allele was a risk factor for obesity. This polymorphism was associated with body weight, body mass index (BMI), and waist circumference. After stratification by BMI, eutrophic individuals with AA or AG genotypes had higher body weights and waist circumferences than those with GG genotypes. In the case group, no associations were observed, except for stratified subjects with morbid obesity that exhibited a progressive increase of body weight, BMI, and waist circumference when rs182052 A was present. No associations were observed between SNPs in RARRES2 and PPARGC1 and obesity or any other studied variables. The rs182052 polymorphism in ADIPOQ is associated with a higher risk for obesity and obesity-related parameters.

Objective: The beneficial effects of estrogen on endothelial function depend on its integrity. This study evaluates the short-term effects of low-dose transdermal estradiol on endothelial function, insulin sensitivity, and blood viscosity in nondiabetic overweight/obese women., Methods: Forty-four nondiabetic overweight/obese women with a history of recent menopause were randomly allocated, in a double-blind fashion, to receive transdermal estradiol (1 mg/d, n = 22) or placebo (n = 22). The following parameters were assessed: endothelial reactivity (venous occlusion plethysmography and nailfold videocapillaroscopy), plasma levels of soluble adhesion molecules, insulin sensitivity (homeostasis model assessment of insulin resistance and areas under the curve of insulin and glucose during an oral glucose tolerance test), and blood and plasma viscosity. Data were expressed as means ± SD or medians [first to third quartiles]., Results: Participants were aged 51.8 ± 2.3 years with a body mass index of 31.5 ± 2.5 kg/m and time since menopause was 3 [2-5] years. At baseline, no differences between the groups were observed; however, after 3 months of treatment, the following changes were observed in the estradiol group compared with the placebo group: a decrease in the forearm vascular resistance at baseline (36.37 [24.9-51.27] vs 51.3 [40.88-70.03] mm Hg/mL per min 100 mL tissue, P < 0.01) and during the postocclusive reactive hyperemia response (15.93 [11.32-22.29] vs 22.13 [16.46-29.7] mm Hg/mL per min 100 mL tissue, P < 0.01), and an increase in red blood cell velocity at rest (0.316 [0.309-0.326] vs 0.303 [0.293-0.308] mm/s, P < 0.001) and during postocclusive reactive hyperemia response (0.374 [0.353-0.376] vs 0.341 [0.333-0.355] mm/s, P < 0.001). Furthermore, blood viscosity was lower in the estradiol group than in the placebo group (3.57 ± 0.12 vs 3.76 ± 0.22 mPa.s; P < 0.01)., Conclusions: Short-term use of low-dose transdermal estradiol in nondiabetic overweight/obese women with a history of recent menopause improved endothelial function and decreased blood viscosity compared with placebo.

Experimental data have shown that simvastatin and artesunate possess activity against Schistosoma mansoni worms in mice fed standard chow. However, little is known regarding the roles of these drugs in mice fed high-fat chow. We have extended past studies by measuring the effects of these drugs on the structural organization of adult schistosomes in hypercholesterolemic mice. For this purpose, mice were gavaged with either simvastatin or artesunate at nine weeks post-infection and were euthanized by cervical dislocation at two weeks post-treatment. Adult worms were then collected and examined by conventional light microscopy, morphometry and confocal laser scanning microscopy. Plasma total cholesterol and worm reduction rates were significantly increased in mice fed high-fat chow compared with their respective control groups. Simvastatin and artesunate caused changes in the tegument, tubercles, and reproductive system (testicular lobes, vitelline glands and ovarian cells), particularly when administered to mice fed high-fat chow. In particular, the tegument and tubercles were significantly thinner in artesunate-treated worms in mice fed high-fat chow compared with mice fed standard chow. This study thus demonstrated that simvastatin and artesunate have several novel effects on the structural organization of adult worms. Together, these results show, for the first time, that simvastatin and artesunate display antischistosomal activity in hypercholesterolemic mice., (Published by Elsevier Inc.)

Objective: We aimed to investigate the effects of low-dose transdermal estrogen on endothelial and inflammatory biomarkers in menopausal overweight/obese women., Methods: We recruited 44 menopausal women (47-55 years; body mass index 27.5-34.9 kg/m(2)) and divided them into estradiol (1 mg/day; n = 22) or placebo groups (n = 22). They were double-blinded, followed and treated for 3 months. At baseline and post-intervention, inflammatory biomarkers (hs-CRP, IL-1β, IL-6, MCP-1 and TNF-α) and of vascular injury (activated circulating endothelial cells, CEC-a) and repair (endothelial progenitor cells, EPC) were quantified. Resting CECs (CEC-r) were also assessed. Microvascular reactivity and vasomotion were analyzed by laser-Doppler flowmetry., Results: Volunteers (51.8 ± 2.3 years; mean body mass index 31.5 ± 2.5 kg/m(2)) had been menopausal for 3 (range 2-5) years. After treatment, no changes were observed in the placebo group, while levels of CEC-r and EPC increased in the estradiol group. In this group, no changes in inflammatory biomarkers were observed but it required a lower cumulative dose of acetylcholine to achieve peak velocity during endothelial-dependent vasodilatation and there was increased endothelial-independent vasodilatation., Conclusions: The short-term use of low-dose transdermal estradiol therapy in overweight/obese menopausal women increased markers of vascular repair and improved microvascular reactivity without changing the inflammatory biomarkers., Clinical Trial Registration: NCT01295892 at www.clinicaltrials.gov .

The effects of a recreational soccer program (RSP) upon body composition, heart rate variability (HRV), biochemical markers, cardio-respiratory fitness, and endothelial function in obese adolescents were investigated. A randomised controlled clinical trial was conducted with 30 adolescents aged 12-17 years and body mass index (BMI) >2 standard deviations of WHO reference values, which were assigned to RSP (n = 10, 2 girls) and obese control (n = 10, 4 girls) groups. The 12-week RSP included 60-min sessions performed 3 times/week. BMI, waist circumference, blood pressure, blood glucose, lipid profile, insulin, C-reactive protein, HRV, and maximal oxygen consumption (VO2peak) were evaluated following standardised procedures. Body composition was determined by dual-energy X-ray absorptiometry and endothelial function by venous occlusion plethysmography. After intervention, RSP exhibited significant reductions in BMI (-0.7 ± 0.2 kg · m(-2)), waist circumference (-8.2 ± 1.4 cm), %body fat (-2.2 ± 0.4%), systolic blood pressure (-5.0 ± 2.3 mmHg), total cholesterol (-16.2 ± 5.8 mg · dL(-1)), triglycerides (-20.5 ± 12.9 mg · dL(-1)), C-reactive protein (-0.06 ± 0.01 mg · dL(-1)), insulin resistance (HOMA-IR, -1.4 ± 0.6), and sympathetic activity (LF, -13.9 ± 6.6 un) vs. controls (P < 0.05). Significant increase was observed in parasympathetic activity (HF, 13.9 ± 6.6 un), VO2peak (7.9 ± 2.8 ml · kg(-1) · min(-1)), and high-density lipoprotein cholesterol (11.0 ± 6.3 mg · dL(-1)) (P < 0.05). Vascular conductance (19.5 ± 8.1 ml · min(-1) · 100 ml, P = 0.005) increased and vascular resistance (-5.9 ± 2.4 ml · min(-1) · 100 ml, P = 0.041) decreased in RSP, but not in controls. A 12-week recreational soccer intervention was effective to improve biochemical, cardiovascular, and fitness health markers in obese adolescents.

We have reported several changes in neonate or adult offspring after the maternal use of whole flaxseed or its components. However, it is unknown the use of higher oil intake in the neonatal period. Here we evaluated the effects of high maternal intake of flaxseed oil during lactation upon milk and body composition in male and female offspring. Lactating rats were divided into: (1) control (C, n=10), 7% soybean oil; (2) hyper 19% soybean oil (HS, n=10); and (3) hyper 17% flaxseed oil+2% soybean oil (HF, n=10). Dams and offspring were killed at weaning. HS and HF dams, male and female offspring presented lower body weight during lactation. HF mothers presented lower body and visceral fat masses. HF male offspring presented lower body and subcutaneous fat masses. HS and HF milk presented lower triglycerides (TG) and cholesterol. HF male and female offspring showed lower triglyceridemia and insulinemia, but no changes in glycemia and leptinemia. The higher intake of flaxseed oil during lactation reduced the body weight of mothers and offspring, decreases milk lipids and apparently increases insulin sensitivity in this critical period of life. Those changes may explain the previously reported programming effect of maternal flaxseed intake during lactation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aims: Studies have demonstrated that early weaning can promote metabolic syndrome during adulthood and that obesity increases oxidative stress. Thus, we aimed to evaluate redox status in a pharmacological early weaning rodent model programmed for metabolic syndrome at adulthood., Main Methods: Lactating dams were randomly assigned into 2 groups: the early weaning group (BRO), which was treated intraperitoneally with bromocriptine (1 mg/day) to inhibit prolactin secretion for the last 3 days of lactation, and the control group (C), which received the BRO diluent for the same time period. The offspring were killed at 90 (PN90) and 180 (PN180) days after birth., Key Findings: Early weaning induced greater visceral adiposity and dyslipidemia. At PN90, the BRO offspring showed glucose intolerance with normoinsulinemia and increased plasma and liver superoxide dismutase, and liver glutathione peroxidase activities, which reduced the liver malondialdehyde but not the increased plasma malondialdehyde levels. However, the BRO offspring showed insulin resistance at PN180 and increased plasma glutathione peroxidase, liver superoxide dismutase, and catalase activities. These changes reduced the plasma and liver malondialdehyde levels, which aided in hepatocyte architecture preservation. Additionally, we observed that sirtuin 1 was overexpressed in the BRO group at PN90, but the increased expression was not maintained through PN180, which suggests unfavorable metabolic conditions in the older offspring., Significance: Despite the observed obesity and glucose homeostasis dysfunction, our data suggest that the early weaning programming induced by bromocriptine can improve the offspring's redox status and may prevent liver damage during adulthood., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The effects of maternal moderate-low physical training on postnatal development, glucose homeostasis and leptin concentration in adult offspring subjected to a low-protein diet during the perinatal period were investigated. Male Wistar rats (aged 150 d old) were divided into four groups according to maternal group: untrained (NTp, n 8); trained (Tp, n 8); untrained with a low-protein diet (NT+LPp, n 8); trained with a low-protein diet (T+LPp, n 8). The trained mothers were subjected to a protocol of moderate physical training over a period of 4 weeks (treadmill, 5 d/week, 60 min/d, at 65 % VO(2max)) before mating. At pregnancy, the intensity and duration of exercise was progressively reduced (50-20 min/d, at 65-30 % VO(2max)). The low-protein diet groups received an 8 % casein diet, and their peers received a 17 % casein diet during gestation and lactation. The pups' birth weight and somatic growth were recorded weekly up to the 150th day. Fasting blood glucose, cholesterol, serum leptin concentration, glucose and insulin tolerance tests were evaluated. The Tp animals showed no changes in somatic and biochemical parameters, while the NT+LPp group showed a greater abdominal circumference, hyperglycaemia, hypercholesterolaemia, glucose intolerance and lower plasma leptin. In the T+LPp animals, all of those alterations were reversed except for plasma leptin concentration. In conclusion, the effects of a perinatal low-protein diet on growth and development, glucose homeostasis and serum leptin concentration in the offspring were attenuated in pups from trained mothers.

It is known that Ca therapy may have anti-obesity effects. Since early weaning leads to obesity, hyperleptinaemia and insulin resistance, we studied the effect of dietary Ca supplementation in a rat model. Lactating rats were separated into two groups: early weaning (EW) - dams were wrapped with a bandage to interrupt lactation in the last 3 d of lactation and control (C) - dams whose pups had free access to milk during the entire lactation period (21 d). At 120 d, EW and C offspring were subdivided into four groups: (1) C, received standard diet; (2) CCa, received Ca supplementation (10 g of calcium carbonate/kg of rat chow); (3) EW, received standard diet; (4) EWCa, received Ca supplementation similar to CCa. The rats were killed at 180 d. The significance level was at P < 0·05. Adult EW offspring displayed hyperphagia (28 %), higher body weight (9 %) and adiposity (77 %), hyperleptinaemia (twofold increase), hypertriacylglycerolaemia (64 %), hyperglycaemia (16 %), higher insulin resistance index (38 %) and higher serum 25-hydroxyvitamin D₃ (fourfold increase), but lower adiponectinaemia:adipose tissue ratio (44 %). In addition, they showed Janus tyrosine kinase 2 and phosphorylated signal transducer and activator of transcription 3 underexpression in hypothalamus (36 and 34 %, respectively), suggesting leptin resistance. Supplementation of Ca for 2 months normalised these disorders. The EW group had no change in serum insulin, thyroxine or triiodothyronine, and Ca treatment did not alter these hormones. In conclusion, we reinforced that early weaning leads to late development of some components of the metabolic syndrome and leptin resistance. Dietary Ca supplementation seems to protect against the development of endocrine and metabolic disorders in EW offspring, maybe through vitamin D inhibition.

Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m(2). All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols) for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical). Results. Twenty participants (10 men) completed the study. Comparison of pre-post intervention revealed that (1) there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2) the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P = 0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C - standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N - standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D(3) (+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (-37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

The renal function of rats whose mothers had hypoprolactinemia at the end of lactation was evaluated during development. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg twice a day, s.c.) or saline on days 19, 20, and 21 of lactation, and their male offspring were followed from weaning until 180 days old. 1 rat from each of the 12 litters/group was evaluated at 2 time points (90 and 180 days). Body and kidney weights, sodium, potassium, and creatinine were measured. Values were considered significant when p<0.05. Adult BRO-treated offspring presented higher body weight (+10%), lower relative renal weight at 90 and 180 days (-9.2% and -15.7%, respectively), glomerulosclerosis, and peritubular fibrosis. At 90 and 180 days, creatinine clearance was lower (-32% and -30%, respectively), whereas serum potassium was higher (+19% and +29%, respectively), but there were no changes in serum sodium. At 180 days, higher proteinuria (+36%) and serum creatinine levels (+20%) were detected. Our data suggest that prolactin inhibition during late lactation programs renal function damage in adult offspring that develops gradually, first affecting the creatinine clearance and potassium serum levels with further development of hyperproteinuria and higher serum creatinine, without affecting sodium. Thus, precocious weaning programs some components of the metabolic syndrome, which can be a risk factor for further development of kidney disease., (Georg Thieme Verlag KG Stuttgart · New York.)

Exposure to tobacco smoke is related to changes in energy balance regulation and several endocrine dysfunctions. Previously, we showed that maternal nicotine (the main addictive compound of tobacco) exposure exclusively during lactation affects biochemical profiles in mothers, milk, and pups. As the possible consequences for mothers and offspring of maternal smoking during lactation are still unknown, we evaluated the effects of tobacco smoke exposure on nutritional, biochemical, and hormonal parameters in dams and pups at weaning. After 72 h from birth, lactating rats were divided into two groups: smoke-exposed (S) in a cigarette-smoking machine, 4 × 1 h per day throughout the lactation period without pups; control (C), rats were treated the same as the experimental group but exposed to filtered air. Dams and pups were killed at weaning (21 days of lactation). Body weight and food intake were evaluated. Milk, blood, visceral fat, adrenal, and carcass were collected. S dams showed hyperprolactinemia (+50%), hypoinsulinemia (-40%), hypoleptinemia (-46%), as well as lower triglycerides (-53%) and very low-density lipoprotein cholesterol (-50%). Milk of S dams had higher lactose (+52%) and triglycerides (+78%). S pups presented higher body protein (+17%), lower total (-24%) and subcutaneous fat contents (-25%), hypoglycemia (-11%), hyperinsulinemia (+28%), hypocorticosteronemia (-40%), lower adrenal catecholamine content (-40%), hypertriglyceridemia (+34%), higher high-density lipoprotein cholesterol (+16%), and lower low-density lipoprotein cholesterol (-45%). In conclusion, tobacco smoke exposure leads to changes in nutritional, biochemical, and hormonal parameters in dams and, passively through the milk, may promote several important metabolic disorders in the progeny.

Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.

We have shown that maternal nicotine exposure during lactation has long-lasting effects on body adiposity and hormonal status of rat offspring. Here, we studied the nutritional and hormonal profiles in this experimental model. Two days after birth, osmotic minipumps were implanted in lactating rats divided into two groups: NIC - continuous s.c. infusions of nicotine (6 mg/kg per day) for 14 days and C - saline. Dams and pups were killed at 15 and 21 days of lactation. Body weight and food intake were evaluated. Milk, blood, visceral fat, carcass, and adrenal gland were collected. All the significant data were P<0.05. At the end of nicotine exposure (15 days), dams presented higher milk production, hyperprolactinemia, and higher serum high-density lipoprotein cholesterol (HDL-C). Milk from NIC dams had higher lactose concentration and energy content. After nicotine withdrawal (21 days), dams showed lower food intake and hyperleptinemia. The 15-day-old NIC pups presented higher total body fat, higher HDL-C, serum leptin, serum corticosterone, and adrenal catecholamine content, but lower tyrosine hydroxylase protein levels. The 21-day-old NIC pups had higher body protein content and serum globulin. Thus, maternal nicotine exposure during lactation results in important changes in nutritional, biochemical, and hormonal parameters in dams and offspring. The pattern of these effects is clearly distinct when comparing the nicotine-exposed group to the withdrawal group, which could be important for the programming effects observed previously.

Neonatal protein restriction causes lower body weight and hormonal dysfunctions in 6 months-old rats. In this model, we studied the body composition, glycogen content, serum lipid, serum protein, and hormones related to glucose homeostasis in the offspring during development. At birth, lactating rats were divided into: control dams - fed a normal diet (23% protein) and protein restricted dams - fed a diet with 8% protein. After weaning, pups received normal diet. Offspring were killed at 21, 90, and 180 days-old. Protein restricted offspring showed lower visceral fat (90th day: 14%; 180th day: 19%) and lower total fat (90th day: 16%; 180th day: 14%) that explain their lower body weight. They presented lower glycemia (180th day: 17%), lower insulinemia (21st day: 63%; 180th day: 24%), higher adiponectinemia (21st day: 169%), higher liver glycogen (21st day: 104%), and higher muscle glycogen (180th day: 106%), suggesting a higher insulin sensitivity. The higher serum corticosterone (50%), higher adrenal total catecholamines content (98%) as well as in vitro catecholamine secretion (26%) of adult protein restricted offspring, suggest a programming stimulatory effect upon adrenal gland. They also presented several biochemical changes, such as lower serum total protein, albumin and globulin (21st day: 17, 21, 12%, respectively), higher LDL-c (21st day: 69%), lower triglycerides (21st day: 42%; 90th day: 39%), and lower total cholesterol (180th day: 16%). Thus, maternal protein restriction during lactation induces an energy-protein malnutrition, characterized by an impairment of the pup's protein anabolism and, after weaning, the lower adiposity suggests lower lipogenesis and higher lipolytic activity, probably caused by catecholamine and glucocorticoid action., (Georg Thieme Verlag KG Stuttgart. New York.)

Neonatal malnutrition is associated with metabolic syndrome in adulthood. Maternal hypoprolactinaemia at the end of lactation (a precocious weaning model) caused obesity, leptin resistance and hypothyroidism in adult offspring, suggesting an association of prolactin (PRL) and programming of metabolic dysfunctions. Metabolic syndrome pathogenesis is still unclear, but abdominal obesity, higher triglycerides, lower high-density lipoprotein (HDL-c) and insulin resistance have been proposed to be important factors involved. We studied the consequences of maternal hypoprolactinaemia during lactation on parameters associated with metabolic syndrome. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg twice a day) or saline on days 19, 20 and 21 of lactation and their offspring were followed from weaning until 180 days old. Adult BRO offspring had higher body weight (+10%, P < 0.05), total body fat (+41%, P < 0.05), visceral fat (+20%, P < 0.05), subcutaneous fat (+3 times, P < 0.05) and total body protein (+24%, P < 0.05). BRO group presented hyperglycaemia (+16%, P < 0.05), lower muscle glycogen (51%, P < 0.05), higher cholesterol (+30%, P < 0.05), higher low-density lipoprotein (LDL-c) (+1.5 times, P < 0.05), higher triglycerides (+49%, P < 0.05), lower HDL-c (28%, P < 0.05), hyperleptinaemia (+2.9 times, P < 0.05), hypoadiponectinaemia (16%, P < 0.05) and hypoprolactinaemia (54%, P < 0.05) as well as higher insulin resistance index (+24%, P < 0.05). Regarding adrenal function, BRO rats showed hypercorticosteronaemia (+46%, P < 0.05) and higher total catecholamine (+37%, P < 0.05). In the hypothalamus, no change was observed in protein expression of the leptin signalling pathway. Thus, neonatal malnutrition induced by maternal PRL inhibition during late lactation programs for obesity, dyslipidaemia and insulin resistance in adult offspring increasing the risk for metabolic syndrome development.

Epidemiological studies show a higher prevalence of obesity in children from smoking mothers and smoking may affect human thyroid function. To evaluate the mechanism of smoking as an imprinting factor for these dysfunctions, we evaluated the programming effects of maternal nicotine (NIC) exposure during lactation. Two days after birth, osmotic minipumps were implanted in lactating rats, divided into: NIC (6 mg/kg per day s.c.) for 14 days; Control - saline. All the significant data were P<0.05 or less. Body weight was increased from 165 days old onwards in NIC offspring. Both during exposure (at 15 days old) and in adulthood (180 days old), NIC group showed higher total fat (27 and 33%). In addition, NIC offspring presented increased visceral fat and total body protein. Lipid profile was not changed in adulthood. Leptinemia was higher at 15 and 180 days old (36 and 113%), with no changes in food intake. Concerning the thyroid status, the 15-days-old NIC offspring showed lower serum-free tri-iodothyronine (FT(3)) and thyroxine (FT(4)) with higher TSH. The 180-days-old NIC offspring exhibited lower TSH, FT(3), and FT(4)). In both periods, liver type 1 deiodinase was lower (26 and 55%). We evidenced that NIC imprints a neonatal thyroid dysfunction and programs for a higher adiposity, hyperleptinemia, and secondary hypothyroidism in adulthood. Our study identifies lactation as a critical period to NIC programming for obesity, with hypothyroidism being a possible contributing factor.

Background: To investigate the effects of low-intensity exercise on bone healing during a short time., Material/methods: We made a surgical 1-mm perforation in the upper third medial cortical of the right tibia of 45 male Wistar rats (3 months old; mean weight, 282+/-34 g). Animals were randomly assigned to a swimming exercise group (SWIM, n=15), a running exercise group (RUN, n=15), or a no exercise control group (CON, n=15). Treatment sessions (10 minutes/day, 5 days/week) were done for 7, 14, or 21 days. Tibias were removed for radiographic, morphometric, and stereologic analyses. Blood samples were obtained for biochemical analyses., Results: Serum phosphorus levels were higher in animals in the RUN group compared with animals in the SWIM group on the seventh day. On the 14th day, the tibias of the animals in the SWIM and RUN groups exhibited higher radiopacity in radiographic grades than animals in the CON group. No difference in collagen morphometry was verified. On the 21st day, serum alkaline phosphatase levels were higher in animals in the CON group than they were in the exercise groups, and animals in the SWIM and CON groups demonstrated an increase in newly formed bone in comparison to animals in the RUN group., Conclusions: At the 14th day of treatment, weight-bearing exercise, assessed by radiography, was found to be beneficial for bone healing. Results at the 21st day of treatment further supported the benefits of non-weight-bearing exercises, showing that weight-bearing exercise may improve bone repair in rats.

Purpose: To evaluate the alterations on plasmatic lipids levels among rats submitted to total splenectomy isolated or combined with splenic autotransplant receiving standard chow during the postoperative period., Methods: Thirty Wistar rats were divided into three groups: control (C)-- sham-operated, total splenectomy--isolated (TS) or combined with splenic autotransplantation (SA). Since the postoperative period, all animals received standard rat chow manipulated in accordance to the American Institute of Nutrition Rodents Diets (1993). The plasmatic levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and glucose (GLUC) were analyzed before the surgical procedure and after 6 and 12 weeks., Results: All the animals presented significant increase of TG and VLDL levels. In relation to the other parameters there was no difference among the weeks 0 and 12 in the animals of group C. In TS group significant increase was observed in TC and GLUC levels during the experiment. In SA group TC, HDL, and GLUC levels remained unaffected while HDL levels increased., Conclusion: Our findings suggest that isolated total splenectomy alters lipids metabolism in rats fed with standard chow and splenic autotransplantation is effective in restoring its control.