<p>The increasing number of immigrants in Sweden during the past decades has brought the health of different ethnic groups into focus. Many groups of immigrants in Sweden have a higher risk of cardiovascular disease (CVD) and coronary heart disease (CHD) than a Swedish reference group. The objective of this thesis was to study the health status and prevalence of metabolic risk factors among immigrant women from Iran and Turkey in comparison with native-Swedish women. The analyses are based on a cross-sectional study of first-generation immigrant women and women born in Sweden aged 35-64. The women underwent a clinical examination, including blood sampling and anthropometric measurements. Dietary intake was assessed by four repeated 24-hour food intake recalls. </p><p>The results show important ethnic differences in risk factors for CHD and the metabolic syndrome between the immigrant and the Swedish-born women. Immigrant women from Iran and Turkey are heavier, with a higher prevalence of abdominal obesity and an unfavourable lipid profile and a high degree of physical inactivity during leisure-time, which may predispose for a higher incidence of diabetes and atherosclerotic CVD. The associations between dietary variables and metabolic risk factors were generally relatively weak. The degree of underreporting of the energy was significant, especially among immigrant women, which might have attenuated possible associations. The fatty acid profile of the diet and in serum among the immigrant women indicated both favourable and unfavourable features, despite a higher prevalence of obesity and dyslipidemia compared to the Swedish-born women. Signs of oxidative stress and inflammation are evident in the immigrant women from the Middle East. </p><p>With reference to ethnical differences in metabolic risk factors, as demonstrated in this thesis, increased emphasis should be given to modifying the underlying factors such as overweight/obesity and physical inactivity associated with the metabolic syndrome in various immigrant groups. </p>

<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 increasing number of immigrants in Sweden during the past decades has brought the health of different ethnic groups into focus. Many groups of immigrants in Sweden have a higher risk of cardiovascular disease (CVD) and coronary heart disease (CHD) than a Swedish reference group. The objective of this thesis was to study the health status and prevalence of metabolic risk factors among immigrant women from Iran and Turkey in comparison with native-Swedish women. The analyses are based on a cross-sectional study of first-generation immigrant women and women born in Sweden aged 35-64. The women underwent a clinical examination, including blood sampling and anthropometric measurements. Dietary intake was assessed by four repeated 24-hour food intake recalls. The results show important ethnic differences in risk factors for CHD and the metabolic syndrome between the immigrant and the Swedish-born women. Immigrant women from Iran and Turkey are heavier, with a higher prevalence of abdominal obesity and an unfavourable lipid profile and a high degree of physical inactivity during leisure-time, which may predispose for a higher incidence of diabetes and atherosclerotic CVD. The associations between dietary variables and metabolic risk factors were generally relatively weak. The degree of underreporting of the energy was significant, especially among immigrant women, which might have attenuated possible associations. The fatty acid profile of the diet and in serum among the immigrant women indicated both favourable and unfavourable features, despite a higher prevalence of obesity and dyslipidemia compared to the Swedish-born women. Signs of oxidative stress and inflammation are evident in the immigrant women from the Middle East. With reference to ethnical differences in metabolic risk factors, as demonstrated in this thesis, increased emphasis should be given to modifying the underlying factors such as overweight/obesity and physical inactivity associated with the metabolic syndrome in various immigrant groups.

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.

La protéine CD36 est un senseur aux AGLC au niveau des papilles gustatives et des entérocytes, impliqué dans la détection gustative des lipides et dans l’optimisation de la synthèse des CM. Notre 1er objectif a été de déterminer si le syndrome métabolique (MS) était associé à une altération de la détection oro-intestinale des AGLC. A l’aide de modèles murins de MS (régimes riches en AGS), nous avons montré que le MS est associé à une moindre sensibilité gustative aux sucres et aux lipides et à une altération de la synthèse des CM à l’origine d’une hypertriglycéridémie postprandiale. Cette modification est associée à une absence de dégradation de CD36 classiquement médiée par les AGLC. Cette altération conduit à un retard d’induction de l’expression des gènes impliqués dans la synthèse de CM moins bien dégradés au niveau sanguin. Selon nos résultats l’hyperinsulinémie en MS pourrait être à l’origine de l’absence de dégradation de CD36. Au niveau oral il a aussi été montré que l’absence de dégradation de CD36 est associée à une altération de la signalisation calcique probablement à l’origine d’un seuil de détection plus élevé des AGLC. Le MS se caractérise donc par un problème de détection des lipides au niveau de la sphère oro-digestive qui favoriserait hyperphagie et hypertriglycéridémie postprandiale. Le 2e objectif a été de déterminer si le XXS (polyphénols) pouvait prévenir le MS. La supplémentation en XXS diminue la prévalence du MS, du fait d’une action anti-obésité associée à un maintien du seuil de détection des lipides et une augmentation de l’activité. Ainsi, la détection oro-intestinale des lipides semble être une cible pertinente pour lutter contre la mise en place du MS / CD36 is a LCFA sensor in gustatory papillae and enterocytes. CD36 is implicated in the gustatory detection of lipids and in optimized CM synthesis. Our first goal was to determine if the metabolic syndrome (MS) was associated with alteration of the oro-intestinal detection of LCFA. Using a murine model of diet induced MS (saturated high fat diets) we shown that the MS is associated with a decrease in lipids and sugar gustatory sensitivity and an alteration in CM synthesis which contributes to the postprandial hypertriglyceridemia. This modification is associated with an absence of CD36 protein degradation classically triggered by LCFA. This alteration leads to a delay in the stimulation of the gene expression involved in the synthesis of CM less well cleared into the blood. Our data shows that the hyperinsulinemia on MS could cause the abolition of CD36 protein degradation. Other data obtained on gustatory papillae demonstrates that the absence of CD36 degradation is associated with an alteration of the LCFA induced calcium-signaling and that probably causes the increase in LCFA detection threshold. Thus, the MS is characterized by an alterated dietary lipids detection by the oro-intestinal tract which could promote overeating and postprandial hypertriglyceridemia. The second goal was to determine if the XXS (polyphenols) could prevent the appearance of the MS. The XXS supplementation decreases the syndrome prevalence, by exerting an anti-obesity activity associated with a LCFA detection threshold preservation and an increased activity. Thus, dietary lipids detection by gustatory papillae and intestine could represent a relevant target in order to prevent MS appearance

Dietary fat quality influences the risk of type 2 diabetes and cardiovascular disease. A low-grade inflammation is suggested to contribute to the disease development, often accompanied by obesity. Whereas n-3 polyunsaturated fatty acids (PUFA) have been considered anti-inflammatory, n-6 PUFA have been proposed to act pro-inflammatory. Saturated fatty acids (SFA) act pro-inflammatory in vitro. This thesis aimed to investigate effects of different fatty acids on low-grade inflammation in observational and interventional studies. In Paper I and II, fatty acid composition in serum cholesterol esters was used as objective marker of dietary fat quality and related to serum C-reactive protein (CRP) and other circulating inflammatory markers in two population-based cohorts, conducted in middle-aged men and elderly men and women, respectively. In Paper III and IV, the impact of diets differing in fat quality on inflammation and oxidative stress was investigated in randomised controlled studies, in subjects with metabolic syndrome and abdominal obesity. In Paper I and II, a low proportion of linoleic acid (18:2 n-6) in serum was associated with higher CRP concentrations, indicating that a low intake of vegetable fats may be related to low-grade inflammation. High CRP concentrations were also associated with high proportions of palmitoleic (16:1) and oleic (18:1) acids and high stearoyl coenzymeA desaturase index, possibly reflecting altered fat metabolism and/or high SFA intake in this population. When comparing two high-fat diets rich in either saturated or monounsaturated fat, and two low-fat diets with or without long-chain n-3 PUFA supplementation during 12 weeks (Paper III), no differences in inflammation or oxidative stress markers were observed. Moreover, a 10-week intervention (Paper IV) with high linoleic acid intake showed no adverse effects on inflammation or oxidative stress. Instead, interleukin-1 receptor antagonist and tumor necrosis factor receptor-2 decreased after linoleic acid intake compared with a diet high in SFA. The results in this thesis indicate that dietary n-6 PUFA found in vegetable fats is associated with lower inflammation marker levels, and to some extent reduces systemic inflammation when compared with SFA. Supplementation of n-3 PUFA did not exert any systemic anti-inflammatory effects, maybe due to a relatively low dose.