No description available.

Introdução: A terapia antirretroviral (ART) mudou o curso da Aids, porém está associada a alterações metabólicas e aumento do risco de doenças cardiovasculares. Objetivo: Avaliar o efeito da suplementação com ácidos graxos ômega-3 de origem marinha no perfil lipídico, na homeostase da glicose, na distribuição de gordura corporal e nos marcadores inflamatórios de adultos com HIV em ART. Métodos: Artigo 1. Trata-se de uma revisão sistemática da literatura com metanálise. Realizou-se busca por ensaios clínicos na base de dados PubMed; 33 artigos foram localizados, seis cumpriram os critérios de inclusão e quatro apresentavam qualidade metodológica adequada. Foi realizada metanálise com efeitos fixos e descrição das diferenças de médias sumárias (DMS (IC95 por cento )). Artigos 2 e 3. Trata-se de um ensaio clínico aleatorizado e controlado. Foram recrutados 120 adultos com idade entre 19 e 64 anos, de ambos os sexos. Os indivíduos alocados no grupo intervenção foram suplementados por 24 semanas com 3g de óleo de peixe/dia (900mg de ácidos graxos ômega-3) e indivíduos alocados no grupo controle receberam placebo (óleo de soja). Resultados: Artigo 1. Após 8-16 semanas de intervenção com 900-3360mg de ácidos graxos ômega-3/dia, observou-se redução de -80,34mg/dL (IC 95 por cento : -129,08 a -31,60) nas concentrações de triglicérides. A análise agregada de estudos com média de concentração de triglicérides > 300mg/dL no baseline e intervenção com 1800-2900mg de ácidos graxos ômega-3/dia resultou em redução de -129,72mg/dL (IC95 por cento : -206,54 a -52,91). Artigos 2 e 3. Foram considerados nas análises dados de 83 sujeitos. Os modelos multinível não revelaram relação estatisticamente significante entre a suplementação com óleo de peixe e as mudanças longitudinais nas concentrações de triglicérides (p=0,335), LDL-C (p= 0,078), HDL-C (p=0,383), colesterol total (p=0,072), apo B (p=0,522), apo A1 (p=0,420), razão LDL-C/apo B (p=0,107), índice homa-2 IR (p=0,387), IMC (p=0,068), circunferência da cintura (p=0,128), relação cintura/quadril (p=0,359), PCR ultra sensível (p=0,918), fibrinogênio (p=0,148), e fator VIII (p=0,073). Conclusões: Artigo 1. Diferentes doses de ácidos graxos ômega-3 reduziram modo significativo as concentrações de triglicérides, confirmando a potencial aplicabilidade desse nutriente no tratamento da hipertrigliceridemia em pessoas que vivem com HIV em ART. Artigos 2 e 3. Uma dose relativamente baixa de óleo de peixe para pessoas que vivem com HIV em ART não alterou o perfil lipídico, a homeostase da glicose, a distribuição de gordura corporal e a concentração de marcadores inflamatórios. Recomenda-se, em estudos subseqüentes, a avaliação do efeito de doses mais elevadas, bem como a determinação de marcadores inflamatórios mais sensíveis / Background: Although the antiretroviral therapy (ART) revolutionized the care of HIV-infected subjects, it has been associated with metabolic abnormalities and increased risk of cardiovascular diseases. Aims: To review the effects of marine omega-3 fatty acids on lipid profile, insulin resistance and inflammatory markers in subjects living with HIV on ART. Methods: Paper 1. Thirty three articles were found in a PubMed search; six met the inclusion criteria; and four of them were considered of adequate quality and included. Meta-analysis with fixed effects was performed and weighted mean differences (WMD (95 per cent CI)) were described. Paper 2 and 3. The study was conducted in an HIV/Aids care centre affiliated to the Medical School, University of Sao Paulo. This was a randomized controlled trial that assessed the effects of 3g fish oil/day (900mg of omega-3 fatty acids) or 3g soy oil/day (placebo). A hundred and twenty subjects aged between 19 and 64 years were recruited. The statistical analyses were performed in Stata 9. Results: Paper 1. Data from 83 subjects were included in the analyses. The overall reduction on triglyceride concentrations after 8-16 weeks of treatment with 900-3360mg of omega-3/day was WMD=-80.34mg/dL (95 per cent CI: -129.08 to -31.60). The pooled result of studies with mean triglyceride > 300 mg/dL at baseline and 1800-2900mg omega-3/day was WMD=-129.72mg (95 per cent CI: -206.54 to -52.91). Paper 2 and 3. Multilevel analyses revealed no statistically significant relationships between fish oil supplementation and the longitudinal changes in triglyceride (p= 0.335), LDL-C (p= 0.078), HDL-C (p= 0.383), total cholesterol (p=0.072), apo B (p= 0.522), apo A1 (p=0.420), LDL-C/apo B ratio (p=0.107), homa-2 IR index (p=0.387), BMI (p=0.068), waist circumference (p=0.128), waist/hip ratio (p=0.359), hs-CRP (p=0.918), fibrinogen (p=0.148), and VIII factor (p=0.073). Conclusions: Paper 1. Different doses of omega-3 fatty acids reduced significantly triglyceride concentrations confirming the potential applicability of this nutrient on the management of hypertriglyceridemia in HIV-infected subjects on ART. Paper 2 and 3. A relatively low dose of fish oil for HIV subjects on ART did not change lipid profile, insulin resistance, body fat distribution, and inflammatory markers. Further investigations should considerer the assessment of higher doses and more sensitivity inflammatory markers

<p>Uvod: Ftalati su vrsta endokrinih disruptora koji se &scaron;iroko koriste kao plastifikatori i rastvarači ali i kao aditivi brojim proizvodima koji se svakodnevno koriste. Prema dosada&scaron;njim studijama na eksperimentalnim životinjama, ali i u humanoj populaciji, diestri ftalne kiseline utiču na reproduktivni sistem, učestvuju u nastanku insulinske rezistencije i gojaznosti. Sindrom policističnih ovarijuma (PCOS) je najče&scaron;ći endokrinolo&scaron;ki poremećaj reproduktivnog sistema žena u generativnom periodu. Insulinska rezistencija i centralna gojaznost, kao faktori kardiometaboličkog sindroma imaju značajnu ulogu u etiologiji PCOS. Ciljevi: Utvrditi prisustvo metabolita ftalne kiseline kod žena u reproduktivnom periodu u na&scaron;oj sredini, kao i da li postoji povezanost ovih endokrinih disruptora sa antropometrijskim parametrima, parametrima glikoregulacije, lipidima i lipoproteinima seruma, gonadotropinima, polnim hormonima, leptinom i indeksima kardiometaboličkog rizika kod žena sa sindromom policističnih jajnika. Metode: Istraživanje je obuhvatalo 61 ženu sa sindromom policističnih jajnika koje su podeljene u dve podgrupe: 31 ispitanica sa PCOS i prisutnim ftalatnim metabolitima u urinu i 30 ispitanica sa PCOS bez ftalatnih metabolita u urinu. Kontrolnu grupu je činilo 30 zdravih žena. Kod svih ispitanica vr&scaron;ena su antropometrijska merenja (TV, TM, OS) i određivane vrednosti parametara glikoregulacije (glikemija i insulinemija, izačunat je HOMA index), lipidi i lipoproteini seruma (ukupan holesterol, trigliceridi, LDL i HDL holesterol), gonadotropini (LH i FSH), polni hormoni (estradiol i testosteron) i leptin. U proceni kardiometaboličkog rizika kori&scaron;ćena su dva indeksa LAP i VAI. Iz jutarnjeg uzorka urina određivano je prisustvo i koncentracija 10 ftalatnih metabolita: Mono-metil ftalat- MMP, Mono-etil ftalat - MEP, Mono-n-butil ftalat - MBP, Mono-n-propil ftalat- MPP, Mono-izo-amil ftalat - MiAP, Mono-n-amil ftalat - MnAP, Mono-cikloheksil ftalat - MCHP, Monobenzil ftalat- MBzP, Mono-(2-etilheksil) ftalat- MHEP, Mono-n-octil ftalat-MOP. Za statističku obradu podataka kori&scaron;ćeni su odgovarajući parametarski i neparametarski testovi. Rezultati: Kod 51 % ispitanica sa PCOS potvrđeno je prisustvo ftalatnih metabolita u urinu. Najzastupljeniji ftalatni metabolit je bio MEHP, zatim MEP, ali je potvrđeno i prisustvo MMP, MPP i MOP. Kod ispitanica sa PCOS su potvrđene statistički značajne korelacije između ukupnih ftalatnih metabolita i BMI, obima struka, glikemije, insulinemije, HOMA indeksa, ukupnog holesterola, triglicerida, LDL holesterola, leptina i testosterona. Analizom pojedinačnih ftalatnih metabolita utvrđene su pozitivne korelacije između MMP i obima struka, parametara glukoznog metabolizma, ukupnog holesterola, LDL holesterola, triglicerida, LAP i VAI indeksa. Zaključak: Kod žena sa PCOS u reproduktivnom periodu u na&scaron;oj sredini je potvrđeno prisustvo ftalanih metabolita. Najvi&scaron;e koncentracije su verifikovane za MEHP i MEP, ukazujući na visoku ekspoziciju di-etilheksil ftalatu (DEHP) i di-etil ftalatu (DEP). Ukupni ftalati značajno povećavaju vrednosti parametara koje učestvuju u razvoju metaboličkog sindroma kod PCOS, ali i povećavaju kardiovaskularni rizik ovih bolesnica. Direktna, značajna veza je potvrđena između MMP i testosterona, parametara i indeksa kardiometaboličkog sindroma.</p> / <p>Introduction: Phthalates are a type of endocrine disruptor widely used as plasticizers and solvents but also as additives to many products that are used daily. According to previous studies in experimental animals, but also in the human population, phthalic diesters affect the reproductive system, participate in the onset of insulin resistance and obesity. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of the reproductive system of women in the generative period. Insulin resistance and central obesity, as factors of cardiometabolic syndrome, have a significant role in the etiology of PCOS. Objectives: To determine the presence of phthalic acid metabolites in women in the reproductive period in our environment, and whether there is a connection between these endocrine disruptors with anthropometric parameters, glycoregulation parameters, lipids and serum lipoproteins, gonadotrophins, sex hormones, leptin and indexes of cardiometabolic risk in women with polycystic ovarian syndrome. Methods: The study included 61 women with polycystic ovarian syndrome divided into two subgroups: 31 subjects with PCOS and present phthalate metabolites in urine and 30 subjects with PCOS without phthalate metabolites in urine. The control group consisted of 30 healthy women. In all subjects, anthropometric measurements were carried out (TV, TM, WC) and the values of glycoregulation parameters (glycemia and insulinemia, HOMA index), lipids and serum lipoproteins (total cholesterol, triglycerides, LDL I HDL cholesterol), gonadotropins FSH), sex hormones (estradiol and testosterone) and leptin. In the assessment of cardiometabolic risk LAP and VAI indexes were determined. From the morning urine sample, the presence and concentration of 10 phthalate metabolites were determined: Mono-methyl phthalate-MMP, Mono-ethyl phthalate-MEP, Mono-n-butyl phthalate-MBF, Mono-n- propyl phthalate- MPP, Mono-iso-amyl phthalate &ndash; MiAP, Mono-n-amyl phthalate &ndash; MnAP, Mono-cyclohexyl phthalate-MCHP, Monobenzyl phthalate-MBzP, Mono- (2-ethylhexyl) phthalate-MHEP, Mono-n-octyl phthalate-MOP. For statistical data processing, appropriate parametric and non-parametric tests were used. Results: 51% of subjects with PCOS confirmed the presence of phthalate metabolites in urine. The most common phthalate metabolite was MEHP, then MEP, but the presence of MMP, MPP and MOP also was confirmed. In subjects with PCOS, a statistically significant correlations between total phthalate metabolites and BMI, waist circumference, glycemia, insulinemia, HOMA index, total cholesterol, triglyceride, LDL cholesterol, leptin and testosterone were confirmed. By analyzing individual phthalate metabolites, a positive correlations between MMP and waist circumference, glycoregulation parameters, total cholesterol, LDL cholesterol, triglyceride, testosterone and LAP and VAI index were determined. Conclusion: In women with PCOS in the reproductive period, the presence of phthalic metabolites in our environment was confirmed. The highest concentrations were verified for MEHP and MEP, indicating a high exposure of DEHP and DEP. Total phthalates significantly increase the values of parameters involved in the development of metabolic syndrome in PCOS, but also increase the cardiovascular risk of these patients. A direct, significant association was confirmed between MMP and testosterone, parameters and index of cardiometabolic syndrome.</p>

O Diâmetro Abdominal Sagital (DAS) é uma medida antropométrica relacionada com a gordura visceral e empregada para avaliar a obesidade abdominal, uma variável associada à síndrome metabólica. Sua utilização é indicada na prática clínica para avaliação de risco cardiometabólico em adolescentes obesos. OBJETIVO: Verificar a concordância entre o DAS e a circunferência abdominal (CA) na avaliação da obesidade central e sua associação com os critérios da Síndrome Metabólica e HOMA-IR em adolescentes obesos. CASUÍSTICA E MÉTODOS: Estudo de corte transversal constituído por 83 adolescentes obesos entre 14 e 18 anos, (46 do sexo feminino e 37 do sexo masculino) matriculados no Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, nos ambulatórios das Unidades de Endocrinologia Pediátrica e de Adolescentes. Foram submetidos a avaliações antropométricas (IMC, Escore Z do IMC, percentual de gordura corporal, circunferência abdominal, diâmetro abdominal sagital), laboratoriais (HDL-c, triglicérides (TG), glicemia (GLIS) e insulina para o cálculo do HOMA-IR) e de pressão arterial sistólica (PAS) e diastólica (PAD), utilizadas para classificação dos critérios da SM. RESULTADOS: Todos os adolescentes apresentaram valores elevados de IMC (36,9±6,7 kg/m2), Z-IMC (+3,27±0,94) e 91,6% da casuística tiveram valores alterados no percentual de gordura corporal (41,4% para o grupo feminino e 36% para o grupo masculino), confirmando a obesidade grave do grupo. Considerando o percentil >=90 do Center for Disease Control and Prevention (CDC), no National Health and Nutrition Examination Survey (NHANES 2011-2014), 85,5% dos adolescentes apresentaram valores elevados de CA (117,7 ± 14,7) e 89,2% valores alterados no DAS (26,9±3,7). Quanto às variáveis laboratoriais, 32,5% dos pacientes apresentaram diminuição de HDL-c e níveis aumentados de: TG (10,8%); GLIS (3,6%); PAS (32,5%,); PAD (21,7%) e HOMA-IR (79,5%), considerando toda a amostra. De acordo com os critérios utilizados pelo International Diabetes Federation, 27,7% da casuística apresentou SM. O DAS demonstrou estar significantemente correlacionado com as variáveis PAS (r=0,489 p < 0,001), PAD(r=0,277 p 0,011) e HOMA-IR (r=0,462 p < 0,001) nos grupos geral, feminino, masculino, com e sem SM. A correlação encontrada entre as medidas do DAS e CA no grupo geral e feminino foi de r = 0,91 (p 0,000) e, no grupo masculino, de r = 0,93 (p 0,000). A concordância entre a CA e o DAS é significante (Kappa k = 0.511; p < 0,001). Nos grupos geral, feminino e masculino com SM, a concordância é mais expressiva (Kappa k = 1,00; p < 0,001.). Esses resultados mostram que os adolescentes apresentavam risco cardiometabólico aumentado e expressiva obesidade central, identificada pelo DAS e CA, apesar de 73,5% deles estarem medicados. O DAS oferece vantagem metodológica na sua mensuração. CONCLUSÕES: Nas condições deste estudo, conclui-se que: as medidas antropométricas CA e DAS se equivalem para o grupo de adolescentes avaliados na classificação da SM; O DAS é preditor de PAS, PAD e HOMA-IR e forte indicador de risco cardiometabólico em adolescentes obesos / The sagittal abdominal diameter (SAD) is an anthropometric measure related to visceral fat and used to evaluate abdominal obesity, a variable associated with the metabolic syndrome. Studies have suggested its employment in the clinical practice for estimating cardiometabolic risk of obese adolescents. OBJECTIVE: To verify the concordance between SAD and abdominal circumference in the assessment of central obesity and its association with the Metabolic Syndrome cluster and with HOMA-IR in obese adolescents. CASUISTICS AND METHODS: In a cross-sectional study, 83 obese adolescents between 14 and 18 years (46 females and 37males) with body mass index (BMI) of 36.9 ± 6.7 kg/m2, followed at the Pediatric Endocrinology Unit and at the Adolescent Unit of the Children\'s Institute, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were submitted to anthropometric (BMI, BMI Z Score, body fat percentage, abdominal circumference, sagittal abdominal diameter), laboratory (HDL-c, triglycerides, glycemia and insulin for calculating HOMA-IR) and systolic and diastolic blood pressure assessments aimed for classification of metabolic syndrome. Previous consentment was given by all patients and their families. RESULTS: All adolescents presented elevated BMI and Z-BMI, and high body fat percentage was displayed by 91.6% of the patients (41.4% for the female group and 36% for the male group), confirming severe obesity. Considering the >= 90 percentile cut-off values as provided by the Anthropometric Reference Data for Children and Adults: United States 2011-2014 for abdominal circumference and SAD, 85.5% of the patients presented high abdominal circumference values (117.7±14.7) and 89.2% presented elevated values of SAD (26.9±3.7). With regard to laboratory variables, 32.5% of the patients displayed decreased HDL-c and increased values of: triglycerides (10.8%); glycemia (3.6%); systolic blood pressure (32.5%); diastolic blood pressure (21.7%) and HOMA-IR (79.5%). According to the criteria of the International Diabetes Federation (IDF), 27.7% of patients presented metabolic syndrome. SAD was significantly correlated with systolic (r=0.489 p < 0.001) and diastolic (r=0.277 p 0.011) blood pressures and HOMA-IR (r=0.462 p < 0.001) in the general, female and male groups, with and without metabolic syndrome. The correlation between SAD and abdominal circumference in the general and female groups was r = 0.91(p 0.000) and in the male group was r = 0.93 (p 0.000). The concordance between SAD and abdominal circumference was significant (Kappa coefficient k = 0.511; p < 0.001). In the general, male and female groups with metabolic syndrome, the concordance was more expressive (Kappa coefficient; k = 1.00 and p < 0.001). These results show that the adolescents presented increased cardiometabolic risk and significant central obesity identified by SAD and abdominal circumference although 73.5% of the studied patients were maintained under medication for clinical metabolic syndrome symptoms. SAD displayed methodological advantages concerning its measurement. CONCLUSIONS: Under the conditions of this study, it is concluded that: the anthropometric measurements of SAD and abdominal circumference are equivalent for metabolic syndrome classification of the studied adolescents; that SAD is a predictor of systolic and diastolic blood pressures and HOMA-IR and is a strong indicator of cardiometabolic risk in obese adolescents

Metabolic syndrome (MetS), a global public health problem, is the primary cause of type 2 diabetes and cardiovascular disorders. Lifestyle modification interventions (dietary and physical activity modifications) are effective in preventing and ameliorating MetS and associated comorbidities. However, the impact of lifestyle changes on MetS among Mexican Americans has yet to be investigated, particularly due to high attrition rates in this population. The overall goal of the explanatory mixed-methods study presented in this dissertation was to identify efficacious lifestyle modification efforts directed towards Mexican Americans to promote their retention in lifestyle modification programs, ameliorate the severity of MetS, and understand underlying behavior modification process. In particular, we examined secondary data from an extensive study Beyond Sabor to 1) examine predictors of program completion, 2) compare variation in MetS severity scores (z-scores) between intervention (Beyond Sabor) and attention control (Healthy Living) groups, over time and, 3) investigate processual development of self-efficacy in a sample of 1153 disadvantaged Mexican Americans participants. Findings suggest that program completers were more likely to be older, had more years of education, lower fasting blood glucose levels, and participated in sites with high group cohesiveness. Results also revealed that when compared with the standard nutrition program, Healthy Living, the lifestyle modification intervention, Beyond Sabor, was more effective in ameliorating MetS severity, systolic blood pressure, triglyceride, and fasting plasma glucose levels among study participants. Qualitative results demonstrate the high acceptability of Beyond Sabor intervention. Four sub-themes emerged illustrating important underlying conditions contributing to participants’ improved self-efficacy: desire to gain knowledge about ways to improve health, development of social support, adoption of program teachings in family lifestyle, and improvement in health outcomes. Findings of the current study may allow researchers to identify Mexican Americans at risk of non-completion and to develop strategies to improve lifestyle modification program attendance, and thus health outcomes. Qualitative findings underscore the importance of sociocultural context on individuals’ attempts to make lifestyle changes to manage their chronic illnesses. Successful adaptation of lifestyle interventions such as Beyond Sabor for at-risk populations in community-based settings will be critical in stemming the tide of MetS.

Insulin resistance is an early marker of Type II diabetes. Excessive lipid accumulation in muscle and liver leads to insulin resistance, and lowering tissue lipids causes an enhancement of insulin action. The enzyme AMP-activated protein kinase (AMPK) is activated when cellular energy levels are compromised, such as during exercise; this enhances fuel oxidation and inhibits energy consuming processes. The hypothesis in this thesis was that activating AMPK in a lipid-induced insulin resistant state leads to tissue lipid reduction and improved insulin sensitivity. Insulin resistant high-fat fed (HF-) rats were administered 5-aminoimidazole-4-carboxamide-1-??-D-ribofuranoside (AICAR), a specific AMPK activator. During an euglycaemic hyperinsulinaemic clamp performed 24h later, HF-rats showed increased whole body, muscle and liver insulin action, independent of changes in PKB-phosphorylation. The liver had reduced triglycerides, malonyl-CoA and increased IkB-a content. A lowering of muscle malonyl-CoA was consistent with conditions favouring increased lipid utilisation. Normal, chow-fed rats also showed improved insulin action post-AICAR. Further studies showed that basal glucose uptake was not increased 24h after AICAR, suggesting that AMPK activation had caused an increase in insulin sensitivity. Diacylglycerols and triglycerides, but not ceramides, were reduced in the liver of AICAR treated HF-rats, suggesting lipid reduction as a likely mediator of enhanced liver insulin action. These lipid species were not reduced in muscle. AICAR administration to HF-rats lowered plasma glucose and fatty acids (FA) acutely, probably due to increased muscle glucose uptake and FA oxidation. Glycogen was reduced in liver and increased in muscle, suggesting glucose mobilisation from liver to muscle. Adrenergic blockade excluded the sympathetic nervous system in the acute AICAR effects. AMPK was activated in white muscle and liver of HF-rats immediately after AICAR, the same tissues that exhibited later improved insulin sensitivity. Tracer technologies used to investigate glucose and lipid fluxes showed that AMPK activation in white muscle simultaneously increased both glucose and FA uptake and their metabolism, with glucose also being stored as glycogen. The liver showed lower lipid synthesis, consistent with reduced liver lipid accumulation observed 24h post-AICAR. In conclusion, these results suggest that activation of AMPK leads to selective tissue lipid reduction and improved insulin action, and is a potential target for the treatment of insulin resistance and type II diabetes.

<p>The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios.</p><p>In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice.</p><p>This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.</p>

The development of the metabolic syndrome (MetS) and cardiovascular diseases have been suggested to be influenced more by the quality than the amount of dietary fat. The FA composition of serum lipids may be used as biomarkers of dietary fat quality. FAs can, however, also be endogenously synthesized by lipogenic enzymes such as elongases and desaturases. Three desaturases are important in humans: Stearoyl-CoA-desaturase (SCD), ∆6-desaturase (D6D) and ∆5-desaturase (D5D) and surrogate measures of desaturase activities can be estimated as product-to-precursor FA ratios. In this thesis, we demonstrated that high SCD, D6D and low D5D estimated activities predicted MetS 20 years later, as well as cardiovascular and total mortality during a maximum of 33.7 years. The relation between D5D and MetS was independent of lifestyle and BMI, while the relation between SCD, D6D and MetS was confounded by BMI. Serum proportions of palmitic (16:0), palmitoleic (16:1) and dihomo-γ-linoleic acids were higher and the serum proportion of linoleic acid (LA) lower at baseline in those individuals who developed MetS. Further, LA was inversely related to mortality, while palmitic, palmitoleic and dihomo-γ-linoleic acids were directly associated with mortality. We also demonstrated that a diet rich in saturated fat “induced” a similar serum FA pattern (including estimated desaturase activities) that was associated with MetS, cardiovascular disease and mortality. We also propose that the SCD ratio [16:1/16:0] might be a novel and useful marker of dietary saturated fat, at least in Western high-fat diets. Finally, genetic variations in the human SCD1 gene were linked to obesity and insulin sensitivity, results that agree with data in SCD1 deficient mice. This thesis suggests that dietary fat quality and endogenous desaturation may play a role in the development of metabolic and cardiovascular diseases and the results support current dietary guidelines.

L’estil de vida que durant les últimes dècades s’està imposant a la nostra societat afavoreix el desequilibri del balanç energètic i en conseqüència l’aparició de la síndrome metabòlica, amb les implicacions que suposa no només en salut pública sinó també a nivell socioeconòmic. Malgrat que existeixen treballs que evidencien afectes beneficiosos sobre paràmetres de la síndrome metabòlica atribuïts al consum de soja i te verd, les vies moleculars d’actuació dels seus principals biocompostos no han estat encara totalment caracteritzades. En aquesta tesi s’ha descrit que les vies d’actuació i els mecanismes en els que participen les isoflavones genisteïna, daidzeïna i el seu metabòlit equol, contribuirien a una millora de la hiperglucèmia, la hiperlipidèmia, la inflamació i l’esteatosi hepàtica, importants components de la fisiopatologia de la síndrome metabòlica en humans. Per altra banda, s’ha demostrat que la principal catequina del te verd, el gal•lat d’epigal•locatequina, actua mitjançant la seva autooxidació, com a senyalitzador cel•lular, induint un desacoblament mitocondrial compensat per un augment de l’activació d’AMPK. Aquestes troballes contribueixen a una descripció dels mecanismes d’acció que podrien explicar els efectes beneficiosos sobre les alteracions del metabolisme energètic associats al consum de soja i te verd. / El estilo de vida que durante las últimas décadas se está imponiendo en nuestra sociedad favorece el desequilibrio del balance energético y con ello el desarrollo del síndrome metabólico, cuyas patologías asociadas son la principal causa de muerte en los países desarrollados. Aunque existen trabajos que evidencian efectos beneficiosos sobre parámetros del síndrome metabólico atribuidos al consumo de soja y té verde, las vías moleculares de actuación de sus principales biocompuestos no han sido aún caracterizadas. En esta tesis se ha descrito no sólo las vías sino también los mecanismos mediados por las isoflavonas genisteína, daidzeína y su metabolito equol, en modelos in vitro insulinorresistentes de los principales tejidos diana de la acción insulínica. Por su parte, se ha demostrado que la principal catequina del té verde, el galato de epigalocatequina, actúa mediante su autooxidación, como señalizador celular, induciendo un desacoplamiento mitocondrial, que se compensa por un incremento de la activación de AMPK. Estos hallazgos contribuyen a la descripción más de los mecanismos de acción que podrían explicar los efectos beneficiosos sobre los desajustes del metabolismo energético asociados al consumo de soja y té verde / Changes in Life style during the last decades in our society has lead to a shift of the energy balance directly associated to the development of metabolic syndrome that nowadays are the main cause of death in developed countries. Although beneficial effects of soy and green tea ingestion have been described previously, the molecular mechanisms of their main biocompounds have not been completely characterized yet. The aim of this thesis is to provide knowledge to help dilucidate them. In this context, the mechanism of action of the isoflavones genistein, daidzein and its metabolite equol have been described with potential interest to improve hyperglycemia, hyperlipidemia, inflammation and hepatic steatosis. On the other hand, it has been demonstrated that the main catechin of green tea, epigallocatequin gallate, through its autooxidation products, modifies cell signalling, leading to a mitochondrial uncoupling compensated by activation of AMPK. In conclusion, these findings offer a more detailed description of the action mechanisms that justify part of the beneficial effects of soy and green tea ingestion on alterations of energy metabolism.

Background: Vitamin D deficiency is a concern in the US. Association between vitamin D status and metabolic syndrome (MetS), insulin resistance (IR), and inflammation is unclear in children. Objective: The relationship between serum vitamin D and MetS, C-reactive protein (CRP), and Homeostatic Model Assessment-IR (HOMA-IR) was investigated. Design: Data from 3 cycles of National Health and Nutrition Examination Survey, 2001-2006 for 3700 (1820, boys; 1880, girls) children and adolescents, aged 12-17 y were used to assess prevalence of vitamin D deficiency (<20 ng>/mL) and association between serum vitamin D and prevalence of MetS, various components of MetS, CRP, and HOMA-IR using multivariate regression models. Results: Overall, prevalences of MetS and vitamin D deficiency were 6.1% and 30.5%, respectively. Prevalence of vitamin D deficiency was higher in girls (52%), blacks (74%), non-supplement users (50%), persons who were examined in winter (56%), and persons in the low poverty income ratio group (57%) compared to their counterparts. Serum vitamin D was inversely associated with waist circumference (P<0.001), systolic blood pressure (P=0.009), and HOMA-IR (P=0.003) and positively associated with HDL-cholesterol (P<0.001). Children with lowest serum vitamin D are at increased risk for MetS (P=0.04; OR 2.26; 95% CI: 1.11, 4.61). Serum vitamin D was not related to CRP (P<0.10). Conclusions: Children with poor vitamin D status are at increased risk for MetS and IR. Because of negative health outcomes associated with MetS and poor vitamin D status when existed individually or in combination, early detection and intervention of these conditions are paramount, especially in children.