Background: Two-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk. Methods/design: This is a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have elements of metabolic syndrome. Eligible participants will be randomized to receive metformin 850 mg BID (n=75) or placebo (n=75) for 12 months. The primary endpoint is change in breast density, based on magnetic resonance imaging (MRI) acquired fat-water features. Secondary outcomes include changes in serum insulin levels, serum insulin-like growth factor (IGF)-1 to insulin-like growth factor binding protein (IGFBP)-3 ratio, serum IGF-2 levels, serum testosterone levels, serum leptin to adiponectin ratio, body weight, and waist circumference. Exploratory outcomes include changes in metabolomic profiles in plasma and nipple aspirate fluid. Changes in tissue architecture as well as cellular and molecular targets in breast tissue collected in a subgroup of participants will also be explored. Discussion: The study will evaluate whether metformin can result in favorable changes in breast density, select proteins and hormones, products of body metabolism, and body weight and composition. The study should help determine the potential breast cancer preventive activity of metformin in a growing population at risk for multiple diseases.

Metabolic syndrome (MetS) is a group of obesity-related metabolic abnormalities that predisposes to type II diabetes mellitus (T2DM) and cardiovascular disease. The dramatic increase in incidence of obesity and MetS over the last 25 years amidst relatively constant host genetics supports the role for non-genetic factors such as gut microbiota composition as an important contributor to the development of these disorders. Microbiota can interact with the host, in a manner influenced by genetics and diet that result in low-grade chronic inflammation. A critical risk factor for the pathogenesis of obesity and its related MetS involves alteration of gut microbiota composition with increased innate immune system activation in the intestine increasing risk. Diet-induced obesity is often modeled by comparing mice fed high-fat diet (HFD), which is made from purified ingredients, vs. normal chow diet (NCD), which is a low-fat assemblage of relatively unrefined plant and animal products. The mechanism by which HFD promotes adiposity is complex but thought to involve low-grade inflammation and altered gutmicrobiota. Here, I investigated the extent to which physiological effects to which HFD-induced adiposity is driven by fat content per se vs. other factors that differentiate HFD vs. NCD or other compositionally-defined diets (CDD) and, moreover sought to define the mechanisms that drove such effects. Relative to NCD, HFD, and to a lesser but nonetheless significant extent, CDD induced increased adiposity in addition to a rapid and marked loss of cecal and colonic mass, indicating that both lipid content and other aspects of HFD are obesogenic.CDD-induced effects were not affected by adjusting dietary protein levels/types but could be largely eliminated by exchanging insoluble fiber (cellulose) for soluble fiber (inulin). Moreover, replacing cellulose with inulin in HFD protected mice against decreased intestinal mass, hyperphagia and increased adiposity. Such protective effects of inulin correlated with increased levels of short-chain fatty acids, which are the products of bacterial fermentation of inulin. Lack of a microbiota, achieved by use of germ-free mice prevented generation of SCFA and eliminated the beneficial effects of inulin. Together, these results indicate that HFD-induced obesity is promoted by its lack of soluble fiber, which, when present, supports microbiota-mediated intestinal epithelia homeostasis that prevents inflammation driving obesity and MetS.

DIABETES MELLITUS TYPE II IN THE LIGHT OF METABOLIC SYNDROME Author: Eliška Hrnčířová ¹ Tutor: MUDr. PharmDr. Kamil Rudolf, Ph.D. ¹, š ¹ Department of Clinical and Social Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové š II. intern gastroenterology clinic University Hospital Hradec Králové Background: My thesis deals with diabetes mellitus, a common chronic civilization disease, the essence of its creation, including the issue of the treatment, regime measures and it also mentions the associated health problems connected to the diagnosis. The Aim of the study: The main purpose of this work based on a small sample of patients was to verify their level of information and knowledge of the disease, compliance, participation in home blood glucose measurements and to determine the health complications associated with diabetes and its treatment. Methods: The study was carried out by questionnaire in a paper form. Data were obtained in a pharmacy during a short interview with 209 randomly selected diabetics type II. The questionnaire included two main characteristics of respondents (gender, age) and 6 simple targeted questions. Results: In the survey 59 % female and 41% male took part. The mean age of patients was 66.9 years. Respondents were diagnosed with DM on average 11.1...

Dlabajová D., Antioxidants of natural origin influencing metabolic syndrome, Diploma thesis 2015/2016, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, pp. 61. Large amounts of substances are extracted from plants found all over the world that show antioxidant activity, which prohibits the formation of free radicals. This activity could be beneficial in preventing and curing risk factors of metabolic syndrome. The selection of plants with this effect is shown in my diploma thesis (for example Salvia limbata, Lupinus luteus, Rosmarinus officinalis, Pueraria lobata etc.), which is divided into plant extracts, culinary plants and substances with significant antioxidant activity. Keywords: plants, antioxidants, metabolic syndrome

The aim of this thesis is to contribute to the understanding of iron metabolism, as a factor associated with cardiometabolic risk, by undertaking secondary data analyses. The objectives were to identify gaps in existing knowledge in terms of populations studied and alternative iron markers, and to attempt to fill the gaps with additional analyses and interpretation. Serum ferritin was the most widely available measure of iron status but the role of serum transferrin and soluble transferrin receptor (sTfR) levels was considered where available. I have taken a life-course approach with analyses in childhood and adulthood, and have included both intermediate factors such as the metabolic syndrome (MetS), and disease diagnoses of diabetes and cardiovascular disease as outcomes. Chapter one presents a review of empirical research literature on the relationship between iron metabolism and cardiometabolic risk, concepts surrounding iron markers and the study outcomes. This chapter also describes the gaps in understanding the iron-cardiometabolic risk relationship, which are subsequently explored in chapters two to six. Chapter two explores the link between serum ferritin and transferrin and MetS in cross-sectional and prospective studies of 725 Spanish children and 567 Chilean adolescents. I found associations between both ends of the ferritin distribution and MetS or glucose metabolism markers in different paediatric populations. For instance, whereas in the Spanish children there was a decrease of 0.02 SD units in the change of MetS score over time for every SD unit increase in ferritin, in the Chilean male adolescents being in the highest tertile of ferritin (v. the lowest) was associated with an increase of 0.25 SD units of MetS score. Furthermore, sustained high ferritin levels at various time points and gradual increase of ferritin during childhood were associated with higher MetS score in adolescence. The third chapter describes the association between serum ferritin status and MetS in adults in two cross-sectional studies of Scottish populations (2,047 individuals from Shetland Islands and 8,563 subjects from the Scottish Health Surveys (SHeS) 1995- 1998). I also examined the overall association between ferritin, MetS and each MetS component in adults, by conducting a meta-analysis and investigating potential relevant sources of heterogeneity for the association. Interestingly, ferritin levels were positively associated with MetS in the Scottish populations, but the association was not independent of the effect of covariates, mainly body mass index (BMI) and transaminase levels [Men Odds ratio (OR) 95% confidence interval (CI) 1.43(0.83- 2.46); Postmenopausal women OR (95%CI) 1.09(0.62-1.90); Premenopausal women OR (95%CI) 1.02(0.42-2.46), P > 0.05]. The meta-analysis supported this finding by describing hepatic injury markers and BMI as the major attenuating factors of the ferritin-MetS association. Chapter four investigates the association between sTfR or ferritin, and MetS in 725 Croatian adults in a cross-sectional study. There was no evidence of an association between sTfR and MetS [Men OR (95%CI) 1.35(0.90-2.02); Postmenopausal women OR (95%CI) 0.73(0.47-1.15); Premenopausal women OR (95%CI) 0.87(0.66-1.17), P > 0.05]. In contrast serum ferritin, was positively and independently associated with MetS in men and postmenopausal women (P < 0.05) [Men OR (95%CI) 1.78(1.31- 2.42); Postmenopausal women OR (95%CI) 1.71(1.12-2.62); Premenopausal women OR (95%CI) 1.24(0.85-1.80)]. These contrasting results suggest that different iron markers reflect different physiological processes other than iron metabolism. Chapter five evaluates the longitudinal association between serum ferritin and several cardiometabolic disease outcomes (CMDs) in the nationally representative SHeS 1995 and 1998 (n = 6,497). I found an independent positive longitudinal association between ferritin and cerebrovascular disease (CEVD), which was strengthened by using higher cut-points for increased ferritin [higher v. lowest sextile fully adjusted Hazard ratio(HR) 95%CI 2.08 (1.09-3.94), P=0.024], and a not significant association with coronary heart disease (CHD) after adjustment for covariates. My analyses confirmed the widely established association with type 2 diabetes (T2D) [whole sample fully adjusted HR 95% CI 1.59(1.10-2.34), P=0.006], even with serum ferritin within the normal range. The above set of observations confirm ferritin as biomarker mainly related to the development of T2D and identifies the need to investigate the association between ferritin and CEVD in other populations. Chapter six investigates whether ferritin is associated with risk for cardiovascular complications among people with T2D using cross-sectional study designs in two populations with differing baseline cardiovascular risk (Spanish study SIDIAP n=38,617) and (Edinburgh Type 2 Diabetes Study (ET2DS) n= 821) with additional analysis of follow-up data for ET2DS. Interestingly, ferritin levels were negatively associated with prevalence of cardiovascular disease, mainly CHD, in people with T2D in both studies [ET2DS OR (95%CI): 0.80(0.67-0.96), P=0.020; SIDIAP study: 0.85(0.83-0.88), P < 0.001). Ferritin was also negatively associated with incident cardiovascular disease in ET2DS: HR 95% CI: 0.39(0.16-0.93), P=0.035. Therefore, the association between iron status and CMD risk in people with T2D appears to differ from that in general populations in which a positive association has been more commonly described. In conclusion, serum ferritin is associated with cardiometabolic risk in different ways in a variety of populations. Inconsistent associations for other iron markers suggest that iron biomarkers reflect factors other than iron homeostasis that influence cardiometabolic risk. The association between iron markers and MetS appears to differ between populations. This thesis illustrates the complex relationship between iron metabolism markers, MetS and CMD, and identifies the need for further research on the topic in order to extend knowledge about pathophysiology and the potential for measures of iron status as biomarkers for CMD.

Metabolic syndrome (MetS) is a conglomeration of several risk factors for cardiovascular disease, with obesity currently being one of the common causes of disability and death in the United States.1 Underlying the obesity, however, there is metabolic imbalance that could be exacerbating the issue of metabolic syndrome.2 Approximately 34% of adults over 20 years old matched the criteria for metabolic syndrome.3 The risk factors for cardiovascular disease (CVD) associated with metabolic syndrome can, over time, lead to severe CVDs, such as heart failure (HF).4 Metabolic syndrome can also lead to developing metabolic heart disease over time. Understanding the development of cardiac hypertrophy and fibrosis in diet-induced metabolic heart disease allow development of an early treatment of metabolic heart disease (MHD) and HF. This study looked at one potential mediator and its role in cardiac hypertrophy and fibrosis, follistatin-like 3 (FSTL3). FSTL3 is an extracellular antagonist of members of the TGF-β superfamily. The goal of our study was to determine the effect, if any, a knockout of FSTL3 would have on the development of cardiac hypertrophy and fibrosis after a high-fat, high-sucrose diet for five months. FSTL3 knockout mice were given a high-fat, high-sucrose (HFHS) diet for five months. These mice were then sacrificed and their hearts were analyzed for cardiac myocyte hypertrophy and interstitial fibrosis using histological methods. After five months on the HFHS diet, wild-type (WT) mice had cardiac hypertrophy. In FLRG KO mice the diet-induced cardiac hypertrophy was attenuated. WT HFHS-fed mice developed interstitial fibrosis, and FLRG KO HFHS developed more accentuated interstitial fibrosis than WT HFHS diet fed mice. This study is useful in suggesting that FTSL3 contributes to the pathogenesis of cardiac hypertrophy in MHD. FTSL3 may be a useful biomarker for cardiac hypertrophy in patients with suspected MHD, and may be a viable target for therapeutic interventions aimed at decreasing pathologic myocardial hypertrophy.

A síndrome metabólica (SM) é um conjunto de alterações metabólicas caracterizadas por três de cinco fatores sendo estes; obesidade abdominal, resistência à insulina, hiperglicemia, dislipidemia e hipertensão. As alterações fisiopatológicas da SM são importantes fatores de risco para a doença cardiovascular que tem alta prevalência na maioria das populações. Estudos genéticos têm mostrado que polimorfismos em genes envolvidos em vias do metabolismo glicídico e lipídico estão relacionados com maior predisposição à SM, porém há poucos dados na nossa população. O objetivo deste projeto é estudar a relação entre polimorfismos nos genes LEP, FTO, APOA5, ADRB3, TCF7L2, ENPP1, CYP11B2 e PPARG e a SM. Foram avaliados parâmetros antropométricos, composição corporal, perfil metabólico e de adipocinas, em 167 indivíduos com SM e 262 sem SM, 321 mulheres e 108 homens, e idade entre 30 e 70 anos. Amostras de sangue periférico foram utilizadas para extração de DNA e determinações de perfil lipídico, glicêmico e de adipocinas. Os polimorfismos FTO (rs1421085 T>C, rs1558902 T>A, rs17817449 T>G, rs8050136 C>A, rs9939609 T>A e rs9930506 A>G), LEP rs7799039 G>A, APOA5 rs662799 T>C, ADRB3 rs4994 T>C, TCF7L2 rs7903146 C>T, ENPP1 rs1044498 A>C, CYP11B2 rs1799998 A>G e PPARG rs2972162 C>T foram analisados por PCR em tempo real. As frequências gênicas e alélicas dos polimorfismos estudados foram similares entre os grupos com e sem SM (p>0,05). O haplótipo FTO TTTCAG foi mais frequente no grupo SM (4,2%) do que sem SM (<1,0%, p=0,003), sugerindo que os portadores deste haplótipo tem maior risco de desenvolver síndrome metabólica. Maiores valores de índice de massa corporal (IMC), circunferência abdominal (CA) ou razão cintura-quadril (RCQ) foram observadas nos portadores dos polimorfismos FTO rs1481085 (alelo C), FTO rs1558902 (alelo A), FTO rs17817449 (alelo G), FTO rs8050136 (alelo A), FTO rs9939609 (alelo A), LEP rs7799019 (alelo A), TCF7L2 rs7903146 (alelo C) em comparação com os portadores de genótipos ancestrais (p<0,05), principalmente no grupo SM. Além disso, o polimorfismo FTO rs9930506 (alelo G) foi relacionado com maior teor de gordura corporal (p=0,040), no grupo SM. O SNP CYP11B2 rs1799998 (alelo G) foi relacionado com maior concentração sérica de LDL colesterol e menor concentração de apoAI (p<0,05), grupo SM. Enquanto que a variante ENPP1 rs1044498 (alelo C) foi associada com menor trigliceridemia (p=0,024), no grupo sem SM. Portadores do alelo A do SNP LEP rs7799019 tiveram maior insulinemia e maiores valores de HOMA-&#946; e HOMA-IR que os portadores do genótipo GG (p<0,05), em ambos os grupos, sugerindo a relação desta variante com resistência a insulina. Menores concentrações de leptina foram observadas nos portadores dos SNPs LEP rs7799019 (alelo A) (p=0,031) e ENPP1 rs1044498 (alelo C) (p=0,021) grupo SM; e FTO rs9939609 (alelo A) (p=0,047) no grupo sem SM. A variante FTO rs9930506 (alelo G) foi relacionada com maior adiponectinemia (p<0,05), no grupo SM. Enquanto o SNP ENPP1 rs1044498 (alelo C) foi relacionado com menor concentração sérica de adiponectina nos grupos com (p=0,010) e sem (p=0,006) SM. Em síntese, polimorfismos FTO, LEP e TCF7L2 tem importante papel na adiposidade associada com a síndrome metabólica, em nossa população, e junto com as variantes CYP11B2 ENPP1 contribuem para a variabilidade do perfil metabólico e de adipocinas principalmente em indivíduos com SM. / Metabolic syndrome (MS) is a group of metabolic disorders characterized by three of five factors, which are: abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. The pathophysiological changes of MS are important risk factors for cardiovascular disease that has a high prevalence in most populations. Genetic studies have shown that polymorphisms in genes involved in pathways of glucose and lipid metabolism are associated with increased predisposition to MS, but there are few data on our population. The objective of this project is to study the relationship between polymorphisms in LEP, FTO, APOA5, ADRB3, TCF7L2, ENPP1, PPARG and CYP11B2 and the SM. We evaluated anthropometric parameters, body composition, metabolic profile and adipokines in 167 individuals with MS and 262 without MS, 321 women and 108 men, aged between 30 and 70 years. Peripheral blood samples were used for DNA extraction and determination of lipid profile, glycemic and adipokines. The polymorphisms FTO (rs1421085 T>C rs1558902 T>A rs17817449 T>G rs8050136 C>A rs9939609 T>A and rs9930506 A>G), LEP rs7799039 G>A APOA5 rs662799 T>C ADRB3 rs4994 T>C TCF7L2 rs7903146 C>T, ENPP1 rs1044498 A>C CYP11B2 rs1799998 A>G and PPARG rs2972162C G>T were analyzed by real-time PCR. Genic and allelic frequencies of polymorphisms were similar between the groups with and without MS (p> 0.05). The FTO TTTCAG haplotype was more frequent in the SM group (4.2%) than without MS (<1.0%, p = 0.003), suggesting that carriers of this haplotype have higher risk of developing metabolic syndrome. Higher values of body mass index (BMI), waist circumference (WC) or waist-hip ratio (WHR) were observed in carriers of the FTO rs1481085 polymorphism (C allele), FTO rs1558902 (allele A), FTO rs17817449 (G allele), FTO rs8050136 (allele A), FTO rs9939609 (allele A), LEP rs7799019 (allele A), TCF7L2 rs7903146 (C allele) compared with those with ancestral genotypes (p <0.05), especially in the SM group. In addition, FTO rs9930506 polymorphism (G allele) was associated with higher fat body mass (p = 0.040) in MS group. CYP11B2 SNP rs1799998 (G allele) was associated with increased serum concentration of LDL cholesterol and apoAI lower concentration (p <0.05) SM group. While the ENPP1 variant rs1044498 (C allele) was associated with lower plasma triglycerides (p = 0.024) in the group without MS. Carriers of the A allele of SNP rs7799019 LEP had higher insulin and higher HOMA-&#946; and HOMA-IR than carriers of the GG genotype (p <0.05) in both groups, suggesting the relationship of this variant with insulin resistance. Lower concentrations of leptin were observed in carriers of the LEP SNPs rs7799019 (allele A) (p = 0.031) and ENPP1 rs1044498 (allele C) (p = 0.021) SM group, and FTO rs9939609 (allele A) (p = 0.047) in the group without MS. The variant FTO rs9930506 (G allele) was associated with higher adiponectinemia (p <0.05) in group SM. While the ENPP1 SNPs rs1044498 (C allele) was associated with lower serum concentration of adiponectin in groups with (p = 0.010) and without (p = 0.006) MS. In summary, polymorphisms FTO, TCF7L2 and LEP play an important role in adiposity associated with metabolic syndrome in our population, and along with the CYP11B2 ENPP1 variants contribute to the variability of the metabolic profile of adipokines, especially in individuals with MS.

Type 2 diabetes and metabolic syndrome are the metabolic disorders which constitute a major public health problem in both developed and developing countries. Various studies have suggested the genetic susceptibility to the disorders. The main aim of the thesis was to investigate the putative association of single nucleotide polymorphisms with Type 2 diabetes (T2D), metabolic syndrome (MetS) and the major components of metabolic syndrome. This study used meta‐analysis, polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) and Sanger sequencing methods to analyse the results. The single nucleotide polymorphism rs57829442 of peroxisome proliferator‐activated receptor‐γ coactivator‐1 (PPARGC1A) gene and its relation to risk of type 2 diabetes has been studied in the United Kingdom population. A meta‐analysis of genetic variant rs8192678 (Gly482Ser) of peroxisome proliferator‐activated receptor‐γ coactivator‐1 (PPARGC1A) gene and its association with the components of metabolic syndrome has been studied. An association of the genetic variants rs8192678 (Gly482Ser) of the PPARGC1A gene, rs7903146 of Transcription Factor 7 Like 2 (TCF7L2) gene, rs9939609 of Fat mass and obesity‐associated (FTO) gene and rs1801282 (Pro12Ala) of peroxisome proliferator‐activated receptor gamma (PPARG) gene with the metabolic syndrome and its components has been studied in the Nepalese population. The results showed that variant rs57829442 of PPARGC1A is not associated with T2D in the United Kingdom population. Further investigation with increased sample size is warranted. In the meta‐analysis, the variant rs8192678 (Gly482Ser) of PPARGC1A gene was found to be significantly associated with body mass index (BMI) in Asian populations under dominant genetic model, total cholesterol (TC) in non‐Asian population under recessive genetic model and with fasting plasma glucose (FPG) under a recessive model in overall and non‐Asian populations. No significant association of the variants rs8192678 (Gly482Ser), rs7903146, rs9939609 and rs1801282 (Pro12 Ala) was found associated with MetS under dominant, recessive, co‐dominant and additive models in the Nepalese population. However, the genotypes (AG and AA) of rs8192678 (Gly482Ser) had a statistically significant protective effect on systolic blood pressure. The genotypes with the risk allele of rs9930609 of FTO gene was significantly associated with weight, waist circumference and diastolic blood pressure under dominant genetic model and with BMI under both dominant and recessive genetic models in the Nepalese population. To the best of our knowledge, this is the first study to report the findings in the Nepalese population.

Made available in DSpace on 2014-06-11T19:30:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-11-01Bitstream added on 2014-06-13T19:19:35Z : No. of bitstreams: 1 cambri_lt_dr_rcla.pdf: 6115778 bytes, checksum: d91311fdbb6890a5a464bd78199ad770 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Este estudo teve por objetivo analisar as alterações que a desnutrição fetal provoca na homeostase glicêmica e na capacidade aeróbia, e quais alterações persistem na idade adulta, mesmo após a realimentação, em modelo experimental utilizando ratos. Adicionalmente, visou verificar a susceptibilidade de animais precocemente desnutridos aos efeitos metabólicos da sobrecarga de frutose. Ratas Wistar adultas (90 dias) foram alimentadas durante a prenhez com dieta balanceada (B) - 17% proteína ou hipoproteica (H) - 6% proteína. Imediatamente após o nascimento, as crias do sexo masculino foram distribuídas em grupos de acordo com o regime alimentar até o final do experimento: Balanceada: dieta B durante todo o período experimental; Balanceada/Frutose: dieta B até o nascimento e dieta rica em frutose (F) - 60% frutose até o final do experimento; Hipoproteica/Balanceada: dieta H até o nascimento e dieta B até o final do experimento; Hipoproteica/Frutose: dieta H até o nascimento e dieta F até o final do experimento. Realizou-se duas séries de experimentos, a primeira observando os animais até a idade adulta (90 dias) e a segunda até a idade jovem (60 dias). Os animais foram avaliados quanto a: tolerância à glicose (teste de tolerância à glicose); sensibilidade à insulina (teste de tolerância à insulina) e capacidade aeróbia (teste da máxima fase estável de lactato - MFEL). Foram também analisadas concentrações séricas de glicose, triglicerídeos, colesterol total, LDL-C, HDL-C, ácidos graxos livres, proteínas totais, albumina, concentrações de glicogênio e lipídios totais no fígado; peso e concentração de lipídios totais do tecido adiposo das regiões mesentérica, retroperitonial e subcutânea e metabolismo da glicose pelo músculo sóleo (captação e oxidação da glicose, síntese e concentração de glicogênio)... (Resumo completo, clicar acesso eletrônico abaixo / This study aimed to analyze the alterations that the fetal malnutrition causes in the glycemic homeostasis and in the aerobic capacity, and if this changes persist into adulthood, after the nutritional recovery in an experimental model using rats. Additionally, it aimed to verify the susceptibility of early malnourished animals metabolic effects of fructose overload. Pregnant Wistar rats were fed with a balanced (B) diet or a low-protein (L) diet. After birth and until the end of the experiment, the male offspring were distributed into four groups according to the diet received: B: B diet during the whole experiment; balanced/fructose (BF): B diet until birth and fructose-rich (F) diet afterwards; low protein/balanced (LB): L diet until birth and B diet afterwards; low protein/fructose (LF): L diet until birth and F diet afterwards. Two series of experiments were performed, in the first the animals were observed until adulthood (90 days) and in the second, until young age (60 days). The animals were evaluated for: glucose tolerance (glucose tolerance test), insulin sensitivity (insulin tolerance test) and aerobic capacity (maximal lactate steady state - MLSS). Serum concentration of glucose, triglycerides, total cholesterol, LDL-C, HDL-C, free fatty acids, total proteins and albumin, liver glycogen and liver total lipids, weight and total lipids in adipose tissue in mesenteric, retroperitoneal and subcutaneous regions, and glucose metabolism by soleous muscle (glucose uptake and oxidation, glycogen concentration and synthesis) were analyzed in two conditions: rest and after acute physical exercise in the intensity of MLSS. The results of the first series of experiments show that early high fructose consumption impaired body weight gain and reduced adipose tissue weight of some regions, independently of the nutritional... (Complete abstract click electronic access below)

Orientador: Roberto Carlos Burini / Banca: Luis Carlos Giarola / Banca: Wilson Luvizotto Medina / Resumo: Verificar quais os principais fatores associados com os maiores valores de uricemia, analisando a dieta, composição corporal e marcadores bioquímicos. Foram estudados 1075 indivíduos, de ambos os sexos, com idade entre 21 e 82 anos, participantes de projeto de mudança de estilo de vida. Ácido úrico, glicose, triglicerídios, colesterol total, uréia, creatinina, gama-GT, albumina e cálcio e HDL-c foram quantificados no soro pelo método de química seca. LDL-c foi calculado pela fórmula de Friedewald. Glóbulos brancos, linfócitos e leucócitos foram quantificados por automação. Proteína C-reativa ultra-sensível (PCR-US) pelo método de imunoquimioluminecência. A avaliação antropométrica foi composta pelas medidas de peso e estatura, com posterior cálculo do IMC. Também mediu-se a circunferência abdominal. Massa muscular e % de gordura pela bioimpedância. A ingestão dietética foi realizada através do recordatório de 24 horas, com posterior cálculo das porções da pirâmide e IAS adaptado. Os testes foram realizados utilizando o programa SAS versão 9.1 e o STATISTICA 6.0 e descritos em média + DP. Foi realizado o teste de ANOVA one-way. A nomalidade da amostra foi avaliada pelo teste de Shapiro-Wilk. Correlação de Pearson simples e parcial. Regressão linear (odds ratio), com intervalo de confiança (IC) de 95%, para observar a razão de chance de apresentar o AU acima do útimo quartil (♂AU > 6,5mg/dL e ♀ AU > 5mg/dL). Análise de regressão múltipla "backward stepwise" para determinação dos principais componentes responsáveis pelo aumento do AU.Os resultados foram discutidos com base no nível de significância de p<0,05. IMC e CA correlacionaram-se positivamente e IMM negativamente com as concentrações de AU ajustadas por sexo, idade e antropometria. Dos componentes dietéticos, apenas % de lipídio polinsaturado apresentou correlação... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: To evaluate the main dietetic, anthropometric and blood chemistry factors associated with the highest uricemia quartile. One thousand and seventy-five male and female individuals were studied. They were 21 to 82 years old and clinically selected to participated in the lifestyle-change program. Uric acid (UA), glucose, triglycerides (TG), total cholesterol, urea, creatinine, gamma-Gt, albumin, calcium and HDL-c were quantified in serum by the dry chemistry method. LDL-c was calculated by the Friedewald's formula. White cells, lymphocytes and leukocytes were quantified by automation. Ultra-sensitive C-reactive protein (US-CRP) was measured by the immunochemiluminescence method. Anthropometric evaluation consisted of weight and height measurements, which was followed by estimation of the body mass index (BMI). Waist circumference (WC) was also measured. Muscle mass (MM) and fat percentages were estimated by bioimpedance. Dietary intake was evaluated by a 24-hour food recall, and the pyramid servings and the adapted health eating index (HEI) were then calculated. Tests were performed by using the SAS software, version 9.1, and STATISTICA and described by mean + SD. The one-way ANOVA test was also carried out. The sample's normality was evaluated by the Shapiro-Wilk's test, and simple and partial Pearson's correlation was also used. Linear regression (odds ratio) with a confidence interval (CI) of 95% was utilized to observe the odds ratio for presenting UA in the last quartile (♂UA > 6.5mg/dL and ♀UA > 5mg/dL). Backward stepwise multiple regression analysis was used to determine the main components responsible for UA increase. Results were discussed based on the level of significance of p<0.05. BMI and WC were positively correlated and the muscle mass index (MMI) was negatively correlated with UA concentrations adjusted for gender, age and anthropometry. Of the dietary components... (Complete abstract click electronic access below) / Mestre