The commercial hydrogenation of oils and fats results in the formation of, among other components, geometrical and positional isomers of monounsaturated fatty acids. The view that there may be hazards associated with such oils have occasionally been expressed. Prior to an investigation of the levels of such acids in human tissue and UK dietary fats, the synthesis of a series of these acids, as standards, and their characterisation, was necessary. For the synthetic programme, the general scheme provided a convenient route for the synthesis of geometrical and positional isomers from common precursors. When condensation of the 1-alkyne and a-chloro-w-iodoalkane was performed via sodamide in liquid ammonia, the scheme was limited but was extended somewhat when performed via methyllithium in dioxan. Generally, yields decreased with the increasing chain length, and migration of the unsaturated bond to the extremities of the resulting molecule. Chromatographic separation, both capillary column GLC and reversephase HPLC, was readily achieved on the basis of chain length and configuration of the double bond. Furthermore, the partial separation of positional isomers was achieved. NMR spectroscopy unambiguously determined the configuration and position of unsaturation in virtually every fatty acid. Assignment is based on the fact that functional groups within an acid alter the chemical shift of neighbouring carbons in a characteristic manner. No one of these techniques alone is applicable to the determination of positional isomerism in a complex lipid mixture and must be used in combination. Whereas NMR is undoubtedly invaluable in the quantification of positional isomers on an individual basis, or in profiling simple mixtures, it is not as applicable to the direct analysis of complex lipid samples. Emphasis on the continuing development of capillary column GLC holds the most promise for the direct quantification of positional isomerism.

O ácido palmitoleico (POA) é descrito como uma lipocina, capaz de melhorar a responsividade à insulina, estimular a oxidação de lipídios e reduzir a inflamação, efeitos essenciais para o controle da doença do fígado gorduroso não alcoólico (NAFLD). Assim, investigamos se o POA pode proteger contra os efeitos deletérios de uma dieta rica em gordura saturada (HF-L) ou gordura trans (HF-T), verificando a participação de PPARα e PPARγ. Para tanto utilizamos camundongos selvagens alimentados com uma dieta padrão (SD), ou animais knockout total de PPARα (PPARαKO) ou com deleção de PPARγ em células mielóides (PPARγKOLyzCre+) alimentados com HF. As dietas foram administradas por 12 semanas, e a partir da 10ª semana os animais foram suplementados com ácido oleico ou POA (300mg/kg). Utilizamos também macrófagos intraperitoneais extraídos de animais WT, PPARαKO e PPARγKOLyzCre+ alimentados com SD com LPS ou LPS + POA (600uM). A HF promoveu resistência à insulina, esteatose e inflamação exacerbada no fígado dos animais, independente do genótipo. Embora não tenha reduzido o acúmulo ectópico de lipídios no fígado, ou modulado a expressão de fatores lipogênicos, POA melhorou a resposta à insulina periférica e hepática. No fígado, POA não modulou fatores da cascata de insulina, ou a produção de adiponectina, porém, estimulou a ativação de AMPK e aumentou os níveis FGF-21, de forma dependente de PPARα. POA reduziu a inflamação hepática, por diminuir TLR4, NFκB e fatores do inflamassoma, mas principalmente, por inibir a polarização de macrófagos do fígado para o fenótipo M1, um efeito que ocorreu mesmo em animais PPARγKOLyzCre+, apesar da maior expressão gênica e proteica de PPARγ observada em macrófagos com POA, in vivo e in vitro. Nossos dados indicam que o POA promove efeitos benéficos contra intolerância à glicose e resistência à insulina hepática e periférica induzida por dieta rica em gordura, por ativação de AMPK, FGF21 e PPARα. E, por reduzir a polarização M1 de macrófagos, independente de PPARs, este ácido graxo 16:1n-7 é capaz de reduzir a inflamação no fígado induzida por dieta hiperlipídica. / Palmitoleic acid (POA) is described as a lipokine, capable of improving insulin responsiveness, stimulating lipid oxidation and reducing inflammation, essential for the control of non-alcoholic fatty liver disease (NAFLD). Thus, we investigated whether POA can protect against the deleterious effects of a diet rich in saturated fat (HF-L) or trans fat (HF-T), verifying the role of PPARα and PPARγ. We used wild-type mice fed a standard diet (SD), or whole-body PPARα knockout (PPARαKO) mice or mice with myeloid cells selective-delected PPARγ (PPARγKOLyzCre+) fed a HF. The diets were administered for 12 weeks, and from the 10th week the animals were supplemented with oleic acid or POA (300mg/kg). Intraperitoneal macrophages extracted from WT, PPARαKO and PPARγKOLyzCre+ mice fed SD and stimulated with LPS or LPS+POA (600μM), were also analyzed. HF promoted insulin resistance, steatosis and exacerbated inflammation in the liver of mice, regardless of genotype. Although it did not reduce the lipids ectopic accumulation in the liver, or modulated the lipogenic factors expression, POA improved the peripheral and hepatic insulin response. In the liver, POA did not modulate factors of the insulin cascade, or adiponectin production, however, stimulated AMPK activation and increased FGF-21 levels, in a PPARα-dependent manner. POA reduced liver inflammation by decreasing TLR4, NFκB and inflammatory factors, but mainly by inhibiting the macrophage polarization of the liver to the M1 phenotype, an effect that occurred even in PPARγKOLyzCre+ mice, despite the increased gene and protein expression of PPARγ observed in macrophages with POA, in vivo and in vitro. Our data indicate that the POA promotes beneficial effects against glucose intolerance and hepatic and peripheral insulin resistance induced by a high fat diet through the activation of AMPK, FGF21 and PPARα. And, by reducing the M1 polarization of macrophages, independent of PPARs, this 16: 1n-7 fatty acid is able to reduce inflammation in the liver induced by high fat diet.

Motivation The objective of the South African Avocado Growers Association (SAAGA) is to increase the demand of avocados by advertising, promoting and other means deemed fit by them. In order to promote and advertise a product, consumer research has to be done to determine the consumers' attitudes towards and beliefs concerning the product. These findings then need to be followed up by scientific studies, targeted at specific problems and target groups to yield scientific evidence. Little consumer research has been done on avocados and studies investigating the health effects of avocados are limited, with available literature only focussing on the cholesterol lowering effect of avocados. Objectives Firstly, the objective is to investigate the beliefs and attitudes of the South African consumer towards avocados and health; to determine whether gender, age group, race or living standard influence the consumers beliefs towards avocados. Secondly, the objective is to dispel the myth that avocados are fattening and should therefore be avoided in energy restricted diets; to examine the effects of avocados, a rich source of monounsaturated fatty acids, as part of an energy restricted diet on weight loss, serum lipids, fibrinogen and vascular function in overweight and obese subjects. Methods Consumer study: One thousand nine hundred and ninety-seven South African individuals, randomly selected from metropolitan areas in South Africa, participated in this survey. Data were weighed to reflect the adult metropolitan population based on gender, age and race distribution. The total population (10 695 000) was representative of both genders (5 423 000 men and 5 272 000 women) and major race groups (2 615 000 whites, 6 252 000 blacks, 1 255 000 coloureds and 573 000 Indians) from different age groups and living standards. The questionnaires were designed by a multidisciplinary team and consisted of seventeen foodrelated questionnaires, of which one questioned the beliefs regarding avocados. Trained field workers administrated questionnaires by conducting face-to-face interviews with consumers. The market research company, MARKINOR, was contracted to collect the data. Quantitative data was statistically analysed in order to generate the relevant descriptive statistics, cross tabulations and statistical tests. SUMMARY Dietary intervention study: Sixty one free-living volunteers (13 men; 48 women), with a mean (standard deviation) body mass index (BMI) of 32 (3.9) kg/m2, participated in this randomised, controlled parallel study. The subjects were paired according to gender, BMI and age and randomly assigned to one of two groups. The experimental group consumed 200 g of avocado (1 avocado) per day, substituting 30 g of other mixed dietary fats, and the control group excluded avocado from their energy restricted diet for six weeks. Seven-day isoenergetic menu plans were given according to mean energy requirements of both genders to provide 30% fat, 55% carbohydrates and 15% protein of total energy intake. Anthropometric measurements, physical activity, dietary intakes, blood pressure and arterial compliance were measured with standard methods at the beginning and end of the intervention. Fasting blood samples were drawn at the beginning and end of the intervention period. Results Consumer study: There were no practical significant differences in the consumers responses in terms of gender or age. Practical significant differences were found between different race and LSM (Living Standard Measure) groups for some variables. The overall response of consumers towards the effect of avocados on health, heart health, children's health and the health effects associated with the fat content of avocados were very positive. However, almost half the consumers are still not convinced of or are uncertain as to the cholesterol content of avocados, while 47% of the consumers still believe that avocados are fattening. More than 80% of the consumers agreed that avocados are a good source of vitamins and minerals, and 76% consider avocados to be a good source of fibre. Almost 70% of the consumers agreed that avocados are good for sportsmen and -women. Avocados were seen by 49% of the consumers to be an aphrodisiac. Dietary intervention study: Fifty-five subjects completed the study. Compliance with avocado intake in the experimental group was 94.6%. Anthropometric measurements (weight, body mass index and percentage body fat) decreased significantly in both groups during the study (p<0.001), and the change was similar in both groups. Serum lipid levels (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides), fibrinogen, blood pressure and arterial compliance did not change significantly within or between the two groups. SUMMARY Conclusions Consumer study: There are still a few myths and misconceptions that exist among some consumers regarding avocados, especially with regard to sexual functioning, cholesterol content, and fattening effect of avocados. The agricultural industry can use these results to plan different marketing campaigns focused on certain target groups to change the misperceptions concerning avocados and convey the positive nutritional value of avocados. Dietary intervention study: The consumption of 200 g avocado per day, within an energy restricted diet, does not compromise weight loss when substituted for 30 g of mixed dietary fat. The serum lipid levels, plasma fibrinogen, arterial compliance, as well as systolic and diastolic blood pressure were not affected by weight loss or avocado intake. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Motivation The objective of the South African Avocado Growers Association (SAAGA) is to increase the demand of avocados by advertising, promoting and other means deemed fit by them. In order to promote and advertise a product, consumer research has to be done to determine the consumers' attitudes towards and beliefs concerning the product. These findings then need to be followed up by scientific studies, targeted at specific problems and target groups to yield scientific evidence. Little consumer research has been done on avocados and studies investigating the health effects of avocados are limited, with available literature only focussing on the cholesterol lowering effect of avocados. Objectives Firstly, the objective is to investigate the beliefs and attitudes of the South African consumer towards avocados and health; to determine whether gender, age group, race or living standard influence the consumers beliefs towards avocados. Secondly, the objective is to dispel the myth that avocados are fattening and should therefore be avoided in energy restricted diets; to examine the effects of avocados, a rich source of monounsaturated fatty acids, as part of an energy restricted diet on weight loss, serum lipids, fibrinogen and vascular function in overweight and obese subjects. Methods Consumer study: One thousand nine hundred and ninety-seven South African individuals, randomly selected from metropolitan areas in South Africa, participated in this survey. Data were weighed to reflect the adult metropolitan population based on gender, age and race distribution. The total population (10 695 000) was representative of both genders (5 423 000 men and 5 272 000 women) and major race groups (2 615 000 whites, 6 252 000 blacks, 1 255 000 coloureds and 573 000 Indians) from different age groups and living standards. The questionnaires were designed by a multidisciplinary team and consisted of seventeen foodrelated questionnaires, of which one questioned the beliefs regarding avocados. Trained field workers administrated questionnaires by conducting face-to-face interviews with consumers. The market research company, MARKINOR, was contracted to collect the data. Quantitative data was statistically analysed in order to generate the relevant descriptive statistics, cross tabulations and statistical tests. SUMMARY Dietary intervention study: Sixty one free-living volunteers (13 men; 48 women), with a mean (standard deviation) body mass index (BMI) of 32 (3.9) kg/m2, participated in this randomised, controlled parallel study. The subjects were paired according to gender, BMI and age and randomly assigned to one of two groups. The experimental group consumed 200 g of avocado (1 avocado) per day, substituting 30 g of other mixed dietary fats, and the control group excluded avocado from their energy restricted diet for six weeks. Seven-day isoenergetic menu plans were given according to mean energy requirements of both genders to provide 30% fat, 55% carbohydrates and 15% protein of total energy intake. Anthropometric measurements, physical activity, dietary intakes, blood pressure and arterial compliance were measured with standard methods at the beginning and end of the intervention. Fasting blood samples were drawn at the beginning and end of the intervention period. Results Consumer study: There were no practical significant differences in the consumers responses in terms of gender or age. Practical significant differences were found between different race and LSM (Living Standard Measure) groups for some variables. The overall response of consumers towards the effect of avocados on health, heart health, children's health and the health effects associated with the fat content of avocados were very positive. However, almost half the consumers are still not convinced of or are uncertain as to the cholesterol content of avocados, while 47% of the consumers still believe that avocados are fattening. More than 80% of the consumers agreed that avocados are a good source of vitamins and minerals, and 76% consider avocados to be a good source of fibre. Almost 70% of the consumers agreed that avocados are good for sportsmen and -women. Avocados were seen by 49% of the consumers to be an aphrodisiac. Dietary intervention study: Fifty-five subjects completed the study. Compliance with avocado intake in the experimental group was 94.6%. Anthropometric measurements (weight, body mass index and percentage body fat) decreased significantly in both groups during the study (p<0.001), and the change was similar in both groups. Serum lipid levels (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides), fibrinogen, blood pressure and arterial compliance did not change significantly within or between the two groups. SUMMARY Conclusions Consumer study: There are still a few myths and misconceptions that exist among some consumers regarding avocados, especially with regard to sexual functioning, cholesterol content, and fattening effect of avocados. The agricultural industry can use these results to plan different marketing campaigns focused on certain target groups to change the misperceptions concerning avocados and convey the positive nutritional value of avocados. Dietary intervention study: The consumption of 200 g avocado per day, within an energy restricted diet, does not compromise weight loss when substituted for 30 g of mixed dietary fat. The serum lipid levels, plasma fibrinogen, arterial compliance, as well as systolic and diastolic blood pressure were not affected by weight loss or avocado intake. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Growing evidence suggests that obesity and associated metabolic dysregulation occurs in concert with chronic low-grade inflammation. Toll-like receptors (TLR) are transmembrane receptors that play an important role in innate immunity and the induction of inflammatory responses. Our laboratory has observed that TLR4 expression is elevated in the skeletal muscle of obese humans and is associated with reduced fatty acid (FA) oxidation and increased lipid synthesis. Additionally, activation of this pathway by lipopolysaccharide (LPS), ex vivo, results in a shift in substrate metabolism favoring glucose as an energy substrate and preferential storage of FA in intracellular lipid depots. The purpose of this study was to examine the effects of saturated vs. monounsaturated FA on TLR4 transcription and signaling using ex vivo and in vivo models. C2C12 myotubes were incubated in FA-enriched growth medium with varying ratios of palmitate and oleate for 12 hours. Following FA treatment, cells were either collected for measures of mRNA and protein levels of TLR4 or challenged with LPS (500 ng/mL) for 2 hours to assess TLR4 mediated changes in interleukin-6 (IL-6) and glucose and fatty acid metabolism. TLR4 mRNA and protein content were increased in stepwise fashion with higher palmitate concentration (p<0.05). This was associated with an exacerbated LPS effect on IL-6 mRNA and protein levels, and glucose and fatty acid metabolism. To determine if these effects are translated to an in-vivo model, C57BL/6 mice were fed high saturated fat (HSF), high monounsaturated fat (HMF), and control diets for 10 weeks. Following the dietary intervention, animals were challenged with I.P. injections of either saline or LPS (~25μg/mouse), sacrificed 4 hours post-injection, and red and white gastrocnemius muscle were harvested for measures of expression and protein levels of TLR4 and IL-6, and glucose and fatty acid metabolism. TLR4 mRNA and protein levels were not altered with either the HSF or HMF diets. However, there was a heightened LPS response with regards to increases in IL-6 and TNF-α, and enhanced shifts in substrate metabolism following the HSF diet (p<0.05). These effects were not observed in response to the HMF diet. In conclusion, these data demonstrate that a milieu of high saturated fatty acids results in elevated sensitization of the TLR4 pathway in skeletal muscle. These results provide insight into how a westernized diet, one enriched in saturated fat, may link chronic inflammation with obesity-associated metabolic abnormalities. / Ph. D.

Introdução: Doenças cardiometabólicas são problemas de saúde pública mundial com repercussões sociais e econômicas. Dieta inadequada é apontada como um dos principais fatores de risco modificáveis, de importância central na prevenção destas doenças. Apesar da constatação de que certos nutrientes se associam a doenças, ainda existem dúvidas quanto às relações causais. Objetivos: 1) Revisar a participação dos alimentos e nutrientes na gênese e controle de doenças crônicas não-transmissíveis integrantes da síndrome metabólica (manuscrito 1); 2) Descrever de forma detalhada a estrutura do programa de intervenção interdisciplinar em hábitos de vida, desenvolvido para usuários da rede pública de saúde do município de São Paulo (manuscrito 2); 3) Investigar o efeito de mudanças em fatores dietéticos sobre o metabolismo glicídico, decorrentes de intervenção em hábitos de vida em indivíduos de risco cardiometabólico da rede pública de saúde (manuscrito 3). Métodos: Foram incluídos adultos com diagnóstico de pré-diabetes ou síndrome metabólica sem diabetes em ensaio clínico aleatorizado envolvendo dois tipos de intervenções de 18 meses: tradicional e intensiva. A intervenção tradicional consistiu de consultas trimestrais com endocrinologista; na intensiva, além dos atendimentos médicos, os indivíduos participaram de sessões psicoeducativas em grupo com equipe multiprofissional. As orientações dietéticas visaram à adequação do consumo de gorduras totais (redução de saturadas e trans e elevação de insaturadas) e aumento na ingestão de fibras. As variáveis coletadas nos momentos pré- e pós-intervenção incluíram dados sócio-demográficos, antropométricos, dietéticos e bioquímicos (glicemia de jejum e póssobrecarga, perfil lipídico, insulina, adiponectina, proteína C reativa, IL-6, TNF-, apolipoproteína A1 e B). A dieta foi avaliada por recordatórios de 24 horas, processados pelo Nutrition Data System software. Foram empregados os testes: t de Student, coeficientes de correlações, ANOVA com p de tendência e análises de regressão múltipla para identificar fatores dietéticos associados à melhora do metabolismo glicídico. Resultados: O manuscrito 1 consiste de um capítulo de livro (Nutrição em Saúde Coletiva) abordando aspectos epidemiológicos de doenças do espectro da síndrome metabólica com ênfase em fatores alimentares e estado nutricional. O manuscrito 2 detalha a estrutura, a equipe integrante, as orientações preconizadas e as principais estratégias psicoeducativas utilizadas no programa de intervenção em hábitos de vida desenvolvido (artigo metodológico submetido e website). Análises do manuscrito 3 mostraram que, ao final da intervenção, o aumento na ingestão de ácidos graxos monoinsaturados e fibras solúveis associaramse de forma independente à redução da glicemia de jejum e os primeiros também à melhora da glicemia pós-sobrecarga. Ajustes por medidas antropométricas não alteraram os resultados, o que ocorreu, porém, após inclusão da variável mudança na insulina nos modelos (artigo original). Conclusão: Justifica-se divulgar programas de intervenção como o aqui desenvolvido considerando-se o atual cenário das doenças cardiometabólicas na atualidade. No presente estudo, o aumento na ingestão de ácidos graxos monoinsaturados e de fibras solúveis promoveu benefícios no metabolismo glicídico, independente da adiposidade, ao final da intervenção no estilo de vida. Possíveis mecanismos mediadores destes processos podem incluir principalmente a melhora da sensibilidade à insulina. Dessa forma, nossos achados sugerem fortemente que um aumento factível no consumo destes nutrientes deva ser estimulado como estratégia para a proteção do metabolismo glicídico em indivíduos de risco cardiometabólico / Introduction: Cardiometabolic diseases are global public health problems with social and economic repercussions. Unhealthy diet is seen as one of the main modifiable risk factors, being of central importance for the prevention of these diseases. Despite the evidence that certain nutrients are associated with diseases, causal relationships are still under discussion. Objectives: 1) To review the involvement of foods and nutrients in the genesis and control of non-communicable chronic diseases, that comprise the metabolic syndrome (manuscript 1); 2) To describe in detail the structure of the interdisciplinary intervention program on lifestyle, developed for costumers of public health system of Sao Paulo city (manuscript 2); 3) To investigate the impact of changes in dietary factors on glucose metabolism, induced by a lifestyle intervention in individuals at cardiometabolic risk attended by the public health system (manuscript 3). Methods: Adults with prediabetes or metabolic syndrome without diabetes were included in a randomized clinical trial involving two types of 18-month interventions: a traditional or an intensive one. The traditional intervention consisted of quarterly consultations with an endocrinologist, while in the intensive participants also attended psychoeducational group sessions with a multidisciplinary team, in addition to the medical visits. The dietary recommendations aimed at the adequate intake of fat (reduction of saturated and trans and increase of unsaturated fatty acids) and increase in fiber intake. Socio-demographic, anthropometric, dietary and biochemical (fasting and post-load plasma glucose, lipid profile, insulin, adiponectin, C-reactive protein, IL-6, TNF-, apolipoprotein A1 and B) data were collected at baseline and after 18-month of follow-up. Diet was assessed by 24-h dietary recalls, processed by Nutrition Data System software. Student t test, correlation coefficients, ANOVA with p for trend and multiple linear regressions analyses were employed to identify dietary factors associated with glucose metabolism improvement. Results: Manuscript 1 consists of a book chapter (Nutrition in Public Health) about epidemiological aspects of diseases of the spectrum of metabolic syndrome with emphasis on dietary factors and nutritional status. Manuscript 2 details the structure, professional team, recommendations and the main psychoeducative strategies used in the lifestyle intervention program developed (methodological article submitted and website). Analyses of manuscript 3 showed that the intervention-induced increase in monounsaturated fatty acids and soluble fiber intake were independently associated with reduction on fasting plasma glucose and the former also with 2h-plasma glucose improvement. Adjustment for anthropometric measurements did not change these results but did after including change in insulin in the models (original article). Conclusion: Intervention programs such as the developed herein should be reported taking into consideration the current scenario of cardiometabolic diseases. In the present study, increases in monounsaturated fatty acids and soluble fiber intake promoted benefits in glucose metabolism, independent of adiposity, at the end of the lifestyle intervention. Possible mechanisms mediating these processes may mainly include improvement in insulin sensitivity. Therefore, our findings strongly suggest that a feasible increase in consumption of these nutrients should be encouraged as a strategy for the protection of glucose metabolism in individuals at cardiometabolic risk

Introdução: O PYY é um peptídeo regulador da saciedade produzido pelas células intestinais em resposta à chegada intraluminal de nutrientes. Objetivos: O presente estudo objetivou avaliar o efeito de sobrecargas agudas de gorduras saturadas (SAT) e monoinsaturadas (MUFA) na secreção aguda de PYY em ratos Wistar normais e após insulinorresistência induzida por dieta hiperlipídica. Métodos: Em experimento controlado, ratos Wistar foram submetidos a uma dieta altamente gordurosa (HFD) (55% de gordura) por 19 semanas (n=15) ou à dieta normal (GC) pelo mesmo tempo (ração ad libitum) (n=15). Ao final de 14 semanas foi realizado um experimento cross-over onde foi avaliada a resposta secretória de PYY sérico nos tempos basal e 60 minutos após sobrecarga oral lipídica isovolumétrica, por meio de gavagem, ajustadas para o peso, administrada de forma aleatória, em dias diferentes, constituídas por ácidos graxos saturados (SAT-banha de porco) ou monoinsaturados (MUFA-óleo de oliva) ou água (CONT). Diferenças entre médias e grupos foram avaliadas por meio de ANOVA de medidas repetidas e associação por regressão linear simples. Resultados: Em relação ao PYY, no grupo com dieta normal, ambas sobrecargas MUFA e SAT elevaram a resposta secretória de PYY significativamente em relação aos seus respectivos basais: MUFA-Basal 2,18 (± 0,24) vs. MUFA-60min 2,30 (± 0,26) pg/ml e SAT-basal 2,21 (± 0.25) pg/ml vs. SAT- 60min 2,29 (± 0,22) pg/ml ANOVA múltiplas entradas p= 0,019 intragrupos; entretanto, sem diferença entre grupos MUFA e SAT (ANOVA múltiplas entradas entre-grupos p= 0,314). No grupo HFD por outro lado, a sobrecarga SAT reduziu o PYY: SAT-basal 2,16 (± 0.21) pg/ml vs. SAT-60min 2,11 (± 0,30) pg/ml (p= 0,01,intragrupos) enquanto a sobrecarga MUFA manteve o mesmo aumento MUFAbasal 2,15pg/ml vs. MUFA-60min 2,22 (± 0.22) pg/ml. p=0,019 (intragrupos). A administração de água (CONT) também reduziu o PYY em relação ao basal, tanto com na dieta normal (p= 0,0091) como na dieta (HFD) (p= 0,0091), mas sem diferença entre os grupos (p= 0,7433). Conclusão: Em ratos Wistar, as sobrecargas lipídicas, tanto de MUFA como de gordura saturadas, aumentam agudamente a secreção de PYY. Entretanto, em ratos Wistar tornados insulinorresistentes através de uma dieta altamente rica em gordura saturada, a mesma sobrecarga de gordura saturada perde a capacidade de estimular os níveis de PYY, enquanto à resposta ao MUFA segue preservada. Esta resposta paradoxal a gorduras saturadas poderia representar um dano celular causado pela insulinorresistência ao tecido intestinal interferindo no aparato secretor de PYY em resposta a este nutriente. Estudos no tecido intestinal precisam ser realizados para identificar possíveis fatores envolvidos e suas implicações no controle da saciedade pelo PYY em indivíduos insulinorresistentes. / Background: PYY is a gut peptide released by L-cells from the intestine after a meal. Objective: The present study aimed to evaluate the effect of acute overloads of saturated fatty acids (SAT) and monounsaturated fatty acids (MUFA) on PYY release in normal and diet induced insulin resistant wistar rats. Methods: a nineteen weeks experiment was conducted with 30 wistar rats that were allocated into two groups: high fat diet (HFD group) (n=15) with diet composition of 55% of lard and 45% standard chow and control group (CG) (n=15). Both groups received water and food ad libitum. Later a cross-over experiment was conducted to evaluate PYY secretory response 60 minutes after two different lipid overloads (SAT-lard; MUFAolive oil) and water (CONT), adjusted by weight, all isovolumetric and lipids were isocaloric, randomly administered in different days. Mean differences were analyzed by repeated measures ANOVA and association by simple linear regression. Results: Both MUFA and SAT overloads significantly increased PYY release in the CG in comparison with baselines: MUFA-Baseline 2,18±0,24 vs. MUFA-60min 2,30±0,26pg/ml and SAT-baseline 2,21±0.25pg/ml vs. SAT-60min 2,29±0,22 pg/ml ANOVA multiple entry p=0,019 intra-group, however without difference between MUFA and SAT (ANOVA multiple entry inter-group p=0,314). In the other hand, HFD SAT overload significantly decreased PYY release: SAT-baseline 2,16±0.21 pg/ml vs. SAT-60min 2,11±0,30 pg/ml (p=0,01,intra-group) while MUFA overload was able to keep the increase on PYY release MUFA-baseline 2,15pg/ml vs. MUFA-60min 2,22±0.22 pg/ml. p=0,019 (intra-group). Water overload (CONT) also reduced PYY release in comparison with baseline in both CG (p=0,0091) and HFD (p=0,0091), without difference between them (p= 0,7433). Conclusion: MUFA and SAT overloads increase PYY release after 60 minutes in normal wistar rats. However, when became high fat diet induced insulin resistant the SAT overload looses the capacity to stimulate PYY release, while MUFA response keeps preserved. This paradoxal finding to saturated fatty acids could indicate a cellular damage caused by insulin resistance in the intestinal tissue which compromises PYY secretory apparatus in response to this nutrient. Studies in the intestinal tissue must be conducted in order to identify possible factors involved and its implications in satiety signals PYY mediated in insulin resistance individuals.

Introdução: O PYY é um peptídeo regulador da saciedade produzido pelas células intestinais em resposta à chegada intraluminal de nutrientes. Objetivos: O presente estudo objetivou avaliar o efeito de sobrecargas agudas de gorduras saturadas (SAT) e monoinsaturadas (MUFA) na secreção aguda de PYY em ratos Wistar normais e após insulinorresistência induzida por dieta hiperlipídica. Métodos: Em experimento controlado, ratos Wistar foram submetidos a uma dieta altamente gordurosa (HFD) (55% de gordura) por 19 semanas (n=15) ou à dieta normal (GC) pelo mesmo tempo (ração ad libitum) (n=15). Ao final de 14 semanas foi realizado um experimento cross-over onde foi avaliada a resposta secretória de PYY sérico nos tempos basal e 60 minutos após sobrecarga oral lipídica isovolumétrica, por meio de gavagem, ajustadas para o peso, administrada de forma aleatória, em dias diferentes, constituídas por ácidos graxos saturados (SAT-banha de porco) ou monoinsaturados (MUFA-óleo de oliva) ou água (CONT). Diferenças entre médias e grupos foram avaliadas por meio de ANOVA de medidas repetidas e associação por regressão linear simples. Resultados: Em relação ao PYY, no grupo com dieta normal, ambas sobrecargas MUFA e SAT elevaram a resposta secretória de PYY significativamente em relação aos seus respectivos basais: MUFA-Basal 2,18 (± 0,24) vs. MUFA-60min 2,30 (± 0,26) pg/ml e SAT-basal 2,21 (± 0.25) pg/ml vs. SAT- 60min 2,29 (± 0,22) pg/ml ANOVA múltiplas entradas p= 0,019 intragrupos; entretanto, sem diferença entre grupos MUFA e SAT (ANOVA múltiplas entradas entre-grupos p= 0,314). No grupo HFD por outro lado, a sobrecarga SAT reduziu o PYY: SAT-basal 2,16 (± 0.21) pg/ml vs. SAT-60min 2,11 (± 0,30) pg/ml (p= 0,01,intragrupos) enquanto a sobrecarga MUFA manteve o mesmo aumento MUFAbasal 2,15pg/ml vs. MUFA-60min 2,22 (± 0.22) pg/ml. p=0,019 (intragrupos). A administração de água (CONT) também reduziu o PYY em relação ao basal, tanto com na dieta normal (p= 0,0091) como na dieta (HFD) (p= 0,0091), mas sem diferença entre os grupos (p= 0,7433). Conclusão: Em ratos Wistar, as sobrecargas lipídicas, tanto de MUFA como de gordura saturadas, aumentam agudamente a secreção de PYY. Entretanto, em ratos Wistar tornados insulinorresistentes através de uma dieta altamente rica em gordura saturada, a mesma sobrecarga de gordura saturada perde a capacidade de estimular os níveis de PYY, enquanto à resposta ao MUFA segue preservada. Esta resposta paradoxal a gorduras saturadas poderia representar um dano celular causado pela insulinorresistência ao tecido intestinal interferindo no aparato secretor de PYY em resposta a este nutriente. Estudos no tecido intestinal precisam ser realizados para identificar possíveis fatores envolvidos e suas implicações no controle da saciedade pelo PYY em indivíduos insulinorresistentes. / Background: PYY is a gut peptide released by L-cells from the intestine after a meal. Objective: The present study aimed to evaluate the effect of acute overloads of saturated fatty acids (SAT) and monounsaturated fatty acids (MUFA) on PYY release in normal and diet induced insulin resistant wistar rats. Methods: a nineteen weeks experiment was conducted with 30 wistar rats that were allocated into two groups: high fat diet (HFD group) (n=15) with diet composition of 55% of lard and 45% standard chow and control group (CG) (n=15). Both groups received water and food ad libitum. Later a cross-over experiment was conducted to evaluate PYY secretory response 60 minutes after two different lipid overloads (SAT-lard; MUFAolive oil) and water (CONT), adjusted by weight, all isovolumetric and lipids were isocaloric, randomly administered in different days. Mean differences were analyzed by repeated measures ANOVA and association by simple linear regression. Results: Both MUFA and SAT overloads significantly increased PYY release in the CG in comparison with baselines: MUFA-Baseline 2,18±0,24 vs. MUFA-60min 2,30±0,26pg/ml and SAT-baseline 2,21±0.25pg/ml vs. SAT-60min 2,29±0,22 pg/ml ANOVA multiple entry p=0,019 intra-group, however without difference between MUFA and SAT (ANOVA multiple entry inter-group p=0,314). In the other hand, HFD SAT overload significantly decreased PYY release: SAT-baseline 2,16±0.21 pg/ml vs. SAT-60min 2,11±0,30 pg/ml (p=0,01,intra-group) while MUFA overload was able to keep the increase on PYY release MUFA-baseline 2,15pg/ml vs. MUFA-60min 2,22±0.22 pg/ml. p=0,019 (intra-group). Water overload (CONT) also reduced PYY release in comparison with baseline in both CG (p=0,0091) and HFD (p=0,0091), without difference between them (p= 0,7433). Conclusion: MUFA and SAT overloads increase PYY release after 60 minutes in normal wistar rats. However, when became high fat diet induced insulin resistant the SAT overload looses the capacity to stimulate PYY release, while MUFA response keeps preserved. This paradoxal finding to saturated fatty acids could indicate a cellular damage caused by insulin resistance in the intestinal tissue which compromises PYY secretory apparatus in response to this nutrient. Studies in the intestinal tissue must be conducted in order to identify possible factors involved and its implications in satiety signals PYY mediated in insulin resistance individuals.

Introdução: Doenças cardiometabólicas são problemas de saúde pública mundial com repercussões sociais e econômicas. Dieta inadequada é apontada como um dos principais fatores de risco modificáveis, de importância central na prevenção destas doenças. Apesar da constatação de que certos nutrientes se associam a doenças, ainda existem dúvidas quanto às relações causais. Objetivos: 1) Revisar a participação dos alimentos e nutrientes na gênese e controle de doenças crônicas não-transmissíveis integrantes da síndrome metabólica (manuscrito 1); 2) Descrever de forma detalhada a estrutura do programa de intervenção interdisciplinar em hábitos de vida, desenvolvido para usuários da rede pública de saúde do município de São Paulo (manuscrito 2); 3) Investigar o efeito de mudanças em fatores dietéticos sobre o metabolismo glicídico, decorrentes de intervenção em hábitos de vida em indivíduos de risco cardiometabólico da rede pública de saúde (manuscrito 3). Métodos: Foram incluídos adultos com diagnóstico de pré-diabetes ou síndrome metabólica sem diabetes em ensaio clínico aleatorizado envolvendo dois tipos de intervenções de 18 meses: tradicional e intensiva. A intervenção tradicional consistiu de consultas trimestrais com endocrinologista; na intensiva, além dos atendimentos médicos, os indivíduos participaram de sessões psicoeducativas em grupo com equipe multiprofissional. As orientações dietéticas visaram à adequação do consumo de gorduras totais (redução de saturadas e trans e elevação de insaturadas) e aumento na ingestão de fibras. As variáveis coletadas nos momentos pré- e pós-intervenção incluíram dados sócio-demográficos, antropométricos, dietéticos e bioquímicos (glicemia de jejum e póssobrecarga, perfil lipídico, insulina, adiponectina, proteína C reativa, IL-6, TNF-, apolipoproteína A1 e B). A dieta foi avaliada por recordatórios de 24 horas, processados pelo Nutrition Data System software. Foram empregados os testes: t de Student, coeficientes de correlações, ANOVA com p de tendência e análises de regressão múltipla para identificar fatores dietéticos associados à melhora do metabolismo glicídico. Resultados: O manuscrito 1 consiste de um capítulo de livro (Nutrição em Saúde Coletiva) abordando aspectos epidemiológicos de doenças do espectro da síndrome metabólica com ênfase em fatores alimentares e estado nutricional. O manuscrito 2 detalha a estrutura, a equipe integrante, as orientações preconizadas e as principais estratégias psicoeducativas utilizadas no programa de intervenção em hábitos de vida desenvolvido (artigo metodológico submetido e website). Análises do manuscrito 3 mostraram que, ao final da intervenção, o aumento na ingestão de ácidos graxos monoinsaturados e fibras solúveis associaramse de forma independente à redução da glicemia de jejum e os primeiros também à melhora da glicemia pós-sobrecarga. Ajustes por medidas antropométricas não alteraram os resultados, o que ocorreu, porém, após inclusão da variável mudança na insulina nos modelos (artigo original). Conclusão: Justifica-se divulgar programas de intervenção como o aqui desenvolvido considerando-se o atual cenário das doenças cardiometabólicas na atualidade. No presente estudo, o aumento na ingestão de ácidos graxos monoinsaturados e de fibras solúveis promoveu benefícios no metabolismo glicídico, independente da adiposidade, ao final da intervenção no estilo de vida. Possíveis mecanismos mediadores destes processos podem incluir principalmente a melhora da sensibilidade à insulina. Dessa forma, nossos achados sugerem fortemente que um aumento factível no consumo destes nutrientes deva ser estimulado como estratégia para a proteção do metabolismo glicídico em indivíduos de risco cardiometabólico / Introduction: Cardiometabolic diseases are global public health problems with social and economic repercussions. Unhealthy diet is seen as one of the main modifiable risk factors, being of central importance for the prevention of these diseases. Despite the evidence that certain nutrients are associated with diseases, causal relationships are still under discussion. Objectives: 1) To review the involvement of foods and nutrients in the genesis and control of non-communicable chronic diseases, that comprise the metabolic syndrome (manuscript 1); 2) To describe in detail the structure of the interdisciplinary intervention program on lifestyle, developed for costumers of public health system of Sao Paulo city (manuscript 2); 3) To investigate the impact of changes in dietary factors on glucose metabolism, induced by a lifestyle intervention in individuals at cardiometabolic risk attended by the public health system (manuscript 3). Methods: Adults with prediabetes or metabolic syndrome without diabetes were included in a randomized clinical trial involving two types of 18-month interventions: a traditional or an intensive one. The traditional intervention consisted of quarterly consultations with an endocrinologist, while in the intensive participants also attended psychoeducational group sessions with a multidisciplinary team, in addition to the medical visits. The dietary recommendations aimed at the adequate intake of fat (reduction of saturated and trans and increase of unsaturated fatty acids) and increase in fiber intake. Socio-demographic, anthropometric, dietary and biochemical (fasting and post-load plasma glucose, lipid profile, insulin, adiponectin, C-reactive protein, IL-6, TNF-, apolipoprotein A1 and B) data were collected at baseline and after 18-month of follow-up. Diet was assessed by 24-h dietary recalls, processed by Nutrition Data System software. Student t test, correlation coefficients, ANOVA with p for trend and multiple linear regressions analyses were employed to identify dietary factors associated with glucose metabolism improvement. Results: Manuscript 1 consists of a book chapter (Nutrition in Public Health) about epidemiological aspects of diseases of the spectrum of metabolic syndrome with emphasis on dietary factors and nutritional status. Manuscript 2 details the structure, professional team, recommendations and the main psychoeducative strategies used in the lifestyle intervention program developed (methodological article submitted and website). Analyses of manuscript 3 showed that the intervention-induced increase in monounsaturated fatty acids and soluble fiber intake were independently associated with reduction on fasting plasma glucose and the former also with 2h-plasma glucose improvement. Adjustment for anthropometric measurements did not change these results but did after including change in insulin in the models (original article). Conclusion: Intervention programs such as the developed herein should be reported taking into consideration the current scenario of cardiometabolic diseases. In the present study, increases in monounsaturated fatty acids and soluble fiber intake promoted benefits in glucose metabolism, independent of adiposity, at the end of the lifestyle intervention. Possible mechanisms mediating these processes may mainly include improvement in insulin sensitivity. Therefore, our findings strongly suggest that a feasible increase in consumption of these nutrients should be encouraged as a strategy for the protection of glucose metabolism in individuals at cardiometabolic risk

Introdução: O PYY é um peptídeo regulador da saciedade produzido pelas células intestinais em resposta à chegada intraluminal de nutrientes. Objetivos: O presente estudo objetivou avaliar o efeito de sobrecargas agudas de gorduras saturadas (SAT) e monoinsaturadas (MUFA) na secreção aguda de PYY em ratos Wistar normais e após insulinorresistência induzida por dieta hiperlipídica. Métodos: Em experimento controlado, ratos Wistar foram submetidos a uma dieta altamente gordurosa (HFD) (55% de gordura) por 19 semanas (n=15) ou à dieta normal (GC) pelo mesmo tempo (ração ad libitum) (n=15). Ao final de 14 semanas foi realizado um experimento cross-over onde foi avaliada a resposta secretória de PYY sérico nos tempos basal e 60 minutos após sobrecarga oral lipídica isovolumétrica, por meio de gavagem, ajustadas para o peso, administrada de forma aleatória, em dias diferentes, constituídas por ácidos graxos saturados (SAT-banha de porco) ou monoinsaturados (MUFA-óleo de oliva) ou água (CONT). Diferenças entre médias e grupos foram avaliadas por meio de ANOVA de medidas repetidas e associação por regressão linear simples. Resultados: Em relação ao PYY, no grupo com dieta normal, ambas sobrecargas MUFA e SAT elevaram a resposta secretória de PYY significativamente em relação aos seus respectivos basais: MUFA-Basal 2,18 (± 0,24) vs. MUFA-60min 2,30 (± 0,26) pg/ml e SAT-basal 2,21 (± 0.25) pg/ml vs. SAT- 60min 2,29 (± 0,22) pg/ml ANOVA múltiplas entradas p= 0,019 intragrupos; entretanto, sem diferença entre grupos MUFA e SAT (ANOVA múltiplas entradas entre-grupos p= 0,314). No grupo HFD por outro lado, a sobrecarga SAT reduziu o PYY: SAT-basal 2,16 (± 0.21) pg/ml vs. SAT-60min 2,11 (± 0,30) pg/ml (p= 0,01,intragrupos) enquanto a sobrecarga MUFA manteve o mesmo aumento MUFAbasal 2,15pg/ml vs. MUFA-60min 2,22 (± 0.22) pg/ml. p=0,019 (intragrupos). A administração de água (CONT) também reduziu o PYY em relação ao basal, tanto com na dieta normal (p= 0,0091) como na dieta (HFD) (p= 0,0091), mas sem diferença entre os grupos (p= 0,7433). Conclusão: Em ratos Wistar, as sobrecargas lipídicas, tanto de MUFA como de gordura saturadas, aumentam agudamente a secreção de PYY. Entretanto, em ratos Wistar tornados insulinorresistentes através de uma dieta altamente rica em gordura saturada, a mesma sobrecarga de gordura saturada perde a capacidade de estimular os níveis de PYY, enquanto à resposta ao MUFA segue preservada. Esta resposta paradoxal a gorduras saturadas poderia representar um dano celular causado pela insulinorresistência ao tecido intestinal interferindo no aparato secretor de PYY em resposta a este nutriente. Estudos no tecido intestinal precisam ser realizados para identificar possíveis fatores envolvidos e suas implicações no controle da saciedade pelo PYY em indivíduos insulinorresistentes. / Background: PYY is a gut peptide released by L-cells from the intestine after a meal. Objective: The present study aimed to evaluate the effect of acute overloads of saturated fatty acids (SAT) and monounsaturated fatty acids (MUFA) on PYY release in normal and diet induced insulin resistant wistar rats. Methods: a nineteen weeks experiment was conducted with 30 wistar rats that were allocated into two groups: high fat diet (HFD group) (n=15) with diet composition of 55% of lard and 45% standard chow and control group (CG) (n=15). Both groups received water and food ad libitum. Later a cross-over experiment was conducted to evaluate PYY secretory response 60 minutes after two different lipid overloads (SAT-lard; MUFAolive oil) and water (CONT), adjusted by weight, all isovolumetric and lipids were isocaloric, randomly administered in different days. Mean differences were analyzed by repeated measures ANOVA and association by simple linear regression. Results: Both MUFA and SAT overloads significantly increased PYY release in the CG in comparison with baselines: MUFA-Baseline 2,18±0,24 vs. MUFA-60min 2,30±0,26pg/ml and SAT-baseline 2,21±0.25pg/ml vs. SAT-60min 2,29±0,22 pg/ml ANOVA multiple entry p=0,019 intra-group, however without difference between MUFA and SAT (ANOVA multiple entry inter-group p=0,314). In the other hand, HFD SAT overload significantly decreased PYY release: SAT-baseline 2,16±0.21 pg/ml vs. SAT-60min 2,11±0,30 pg/ml (p=0,01,intra-group) while MUFA overload was able to keep the increase on PYY release MUFA-baseline 2,15pg/ml vs. MUFA-60min 2,22±0.22 pg/ml. p=0,019 (intra-group). Water overload (CONT) also reduced PYY release in comparison with baseline in both CG (p=0,0091) and HFD (p=0,0091), without difference between them (p= 0,7433). Conclusion: MUFA and SAT overloads increase PYY release after 60 minutes in normal wistar rats. However, when became high fat diet induced insulin resistant the SAT overload looses the capacity to stimulate PYY release, while MUFA response keeps preserved. This paradoxal finding to saturated fatty acids could indicate a cellular damage caused by insulin resistance in the intestinal tissue which compromises PYY secretory apparatus in response to this nutrient. Studies in the intestinal tissue must be conducted in order to identify possible factors involved and its implications in satiety signals PYY mediated in insulin resistance individuals.