Secular trends of obesity and cardiovascular risk factors in a Mediterranean population

Objective: To evaluate time trends of obesity, abdominal obesity, and cardiovascular risk factors (CRFs) according to BMI and waist circumference (WC) categories in a Mediterranean population. Research Methods and Procedures: Subjects were Spanish men (n = 2383) and women (n = 2525) 25 to 74 years old, examined in 1994 to 1995 and 1999 to 2000 in two independent population‐based cross‐sectional surveys in the northeast of Spain. Lifestyle measures, CRFs, and anthropometric variables were analyzed. Results: Over the 5 years of the study, mean age‐standardized BMI increased by 1.0 units in men and by 0.8 units in women. At the same time the prevalence of obesity increased from 15.4% to 21.9% in men and from 15.4% to 21.4% in women. An upward trend was observed for WC and abdominal obesity (WC > 102 cm in men and WC > 88 cm in women) only in men. The proportion of men and women with hypercholesterolemia, diabetes, and low high‐density lipoprotein‐cholesterol plasma concentration remained stable within BMI and WC categories. The proportion of hypertension and smoking in obese men significantly increased from 1995 to 2000. Discussion: The 5‐year increase in BMI and WC is of considerable magnitude in the present population, although several CRFs remained stable within BMI and WC categories.     

The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects

The precise orosensory inputs engaged for dietary lipids detection in humans are unknown. We evaluated whether a common single nucleotide polymorphism (rs1761667) in the CD36 gene that reduces CD36 expression and the addition of orlistat, a lipase inhibitor, to reduce FA release from triacylglycerols (TGs), the main component of dietary fats, would attenuate fat orosensory sensitivity in humans. Twenty-one obese subjects with different rs1761667 genotypes (6 AA, 7 AG, and 8 GG) were studied on two occasions in which oleic acid and triolein orosensory detection thresholds were measured using emulsions prepared with and without orlistat. Subjects homozygous for the G-allele had 8-fold lower oral detection thresholds for oleic acid and triolein than subjects homozygous for the A allele, which associates with lower CD36 expression (P = 0.03). Thresholds for heterozygous subjects were intermediate. The addition of orlistat increased detection thresholds for triolein (log threshold = -0.3 ± 0.2 vs. 0.3 ± 0.1; P < 0.001) but not oleic acid (log threshold = -1.0 ± 0.2 vs. -0.8 ± 0.2; P > 0.2). In conclusion, this is the first experimental evidence for a role of CD36 in fat gustatory perception in humans. The data also support involvement of lingual lipase and are consistent with the concept that FA and not TG is the sensed stimulus.     

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population

Abstract

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7′8′-dihydro-2′-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.     

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate–low linkage disequilibrium (D′ = 0.719; r ² = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; P _additive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; P _recessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (P _additive = 0.016, P _recessive = 0.011), low-density lipoprotein cholesterol (P _additive = 0.032, P _recessive = 0.031) and triglycerides (P _additive = 0.040, P _recessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD.     

Food habits of the wildcat (Felis silvestris) in a peculiar habitat: the Mediterranean high mountain

The feeding spectrum of the wildcat Felis silvestris Schreber, 1777 was studied in two sites with different ecological characteristics, both situated in the same Mediterranean environment in the high mountain of the Sierra Nevada National Park, south-east Spain, where the rabbit Oryctolagus cuniculus is absent. Scat analysis ( n =101 faeces; n =402 prey items) showed that the diet is based on rodents, fundamentally wood mouse Apodemus sylvaticus , Mediterranean pine vole Microtus duodecimcostatus and south-western water vole Arvicola sapidus . Results showed strong differences between the two sites (χ²=74.04, d.f.=5, P <0.001), that is a predominance of voles in the mesic Chico river, whereas mice are predominant in the xeric Tejos ravine. Red-legged partridge Alectoris rufa and carrion also played an important role, especially in biomass terms. The overall diet differed essentially from that of the Mediterranean region, which surrounds the study area, since in these areas rabbits constitute the primary prey. However, the diet of the mountain wildcats is similar to that in the Eurosiberian floral region, despite its distance from the Sierra Nevada. In conclusion, the Iberian wildcat seems to behave as a facultative specialist, since it prefers rabbits whenever they are available, but rodents constitute most of its diet if rabbits are scarce or absent.     

Spatiotemporal variation in the population structure of the European hake in the NW Mediterranean

The bathymetric distribution of Merluccius merluccius was studied as a function of length, age and maturity of specimens caught by commercial trawl and longline in Different seasons. Males matured first at 28·8 cm (3 years old), and females at 38·0 cm (3·5 years old). Reproductive activity was noted practically throughout the year with its most pronounced spawning peak in the autumn. Most fish <37–40 cm were males and >46 cm were females. Specimens occurred between 50 and 750 m depth, although density was low at >400 m. Adults were found at all depth strata studied. Recruits and juveniles were limited to inshore waters <400 m, most were found between 100 and 200 m. Spring and summer were the preferred seasons for recruitment; although for both seasons there was some interannual variation. Adult distribution also varied, according to the season. Young adults were spread over the entire depth range, with the biggest ones concentrated at the edge of the shelf (150–350 m), especially in autumn and winter. The main spawning peak coincided with this concentration of adults suggesting that spawning occurred in autumn/winter at the edge of the shelf.     

A risk score to predict type 2 diabetes mellitus in an elderly Spanish Mediterranean population at high cardiovascular risk

Introduction

To develop and test a diabetes risk score to predict incident diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk.

Materials and Methods

A diabetes risk score was derived from a subset of 1381 nondiabetic individuals from three centres of the PREDIMED study (derivation sample). Multivariate Cox regression model ß-coefficients were used to weigh each risk factor. PREDIMED-personal Score included body-mass-index, smoking status, family history of type 2 diabetes, alcohol consumption and hypertension as categorical variables; PREDIMED-clinical Score included also high blood glucose. We tested the predictive capability of these scores in the DE-PLAN-CAT cohort (validation sample). The discrimination of Finnish Diabetes Risk Score (FINDRISC), German Diabetes Risk Score (GDRS) and our scores was assessed with the area under curve (AUC).

Results

The PREDIMED-clinical Score varied from 0 to 14 points. In the subset of the PREDIMED study, 155 individuals developed diabetes during the 4.75-years follow-up. The PREDIMED-clinical score at a cutoff of ≥6 had sensitivity of 72.2%, and specificity of 72.5%, whereas AUC was 0.78. The AUC of the PREDIMED-clinical Score was 0.66 in the validation sample (sensitivity = 85.4%; specificity = 26.6%), and was significantly higher than the FINDRISC and the GDRS in both the derivation and validation samples.

Discussion

We identified classical risk factors for diabetes and developed the PREDIMED-clinical Score to determine those individuals at high risk of developing diabetes in elderly individuals at high cardiovascular risk. The predictive capability of the PREDIMED-clinical Score was significantly higher than the FINDRISC and GDRS, and also used fewer items in the questionnaire.     

Minimal versus umbilical waist circumference measures as indicators of cardiovascular disease risk

Objective: Measures of central obesity are strongly correlated with cardiovascular disease (CVD) risk. Although waist circumference (WC) is a commonly used measure of central obesity, there is no standard measurement location. We examined two WC locations to determine which was more highly correlated with CVD risk factors and metabolic syndrome (MS). Research Methods and Procedures: WC measures were taken on 266 sedentary, overweight men and women 45 to 60 years old. Intravenous glucose tolerance tests, fasting plasma lipid analysis, and computed tomography scans were conducted. Correlational analyses followed by the Test for Equal Correlations determined whether one WC measure better correlated with the cardiovascular risk factors. Results: In women, minimal waist had higher correlation coefficients than umbilical waist for all eight variables presented. High‐density lipoprotein‐cholesterol, low‐density lipoprotein particle size, and MS score were significantly correlated with minimal waist, but not umbilical waist. For high‐density lipoprotein size and insulin sensitivity, minimal waist was a better correlate, although the difference between waist measures only approached statistical significance (p < 0.06). In men, minimal waist had a higher correlation coefficient than umbilical waist for insulin sensitivity, fasting insulin, and visceral adipose tissue. Additionally, minimal waist was significantly correlated with MS in men and umbilical waist was not. For both genders, minimal waist was more highly correlated with visceral adipose tissue than umbilical waist. Discussion: For every metabolic variable presented, minimal WC was more highly correlated with CVD risk than was umbilical WC in women. The data for women indicate that WC location is important when determining CVD risk. In men, minimal waist was better, although the data were less compelling.     

Effects of Obesity Phenotype on Coronary Heart Disease Risk Factors in Response to Weight Loss

Objective: To determine whether there is a difference in risk‐factor improvement for coronary heart disease (CHD) between the intra‐abdominal fat (IF) and subcutaneous fat (SF) obesity phenotypes after weight loss. Research Methods and Procedures: Subjects included 55 mildly obese women (body mass index, 25 to 36 kg/m²; age range, 34 to 63 years) who had at least two of three CHD risk factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220 mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity was classified as ≥110 cm² of the IF area measured; subjects with <110 cm² were classified as having SF obesity. The IF and SF obesity groups were divided into diet‐only and diet‐plus‐exercise groups. Assays and measurements were performed before and after a 14‐week (98‐day) intervention. Results: Weight was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic blood pressure, TC, and low‐density lipoprotein‐cholesterol were significantly reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity than in SF obesity, whereas no differences were observed in the improvement of CHD risk factors. Sample sizes needed for observing a significant difference for SBP, TC, triglycerides, and fasting plasma glucose were greater than the number of subjects in this study. Discussion: Our results suggest that the influence of the obesity phenotype on improving CHD risk factors is not apparent. A larger study is needed to prove the validity of this finding.     

Adiposity and dietary intake in cardiovascular risk in an obese population from a Mediterranean area

The aim of the study was to determine the particular relevance of android fat distribution and dietary intake in cardiovascular risk in an obese Mediterranean population with high intake of monounsaturated fatty acids (MUFA) and to compare the findings with those from normal-weight subjects. For the study, 193 subjects aged 25-60 were selected: 118 obese (BMI > or = 27 kg/m2), and 75 normal-weight (BMI < 25 kg/m2). Cardiovascular risk factors including hypertension, dyslipidaemia, glucose intolerance and insulin resistance were assessed. Nutrient intake and body fat distribution were determined. Results show that MUFA were highly consumed in the total population (21% of total energy). The obese population was normolipidemic and normoinsulinemic. However, cardiovascular risk factors (CVRF) were significantly higher than in normal-weight (P < 0.05). Obese subjects derived a greater percentage of their energy intake from total fat and lower from carbohydrates and saturated fats (P < 0.05). BMI and waist-hip ratio positively correlated with fat percentage of total energy intake and with MUFA (g/100 g fatty acids) in men, indicating that the excess of fat intake in obesity is due to a larger consumption of olive oil. CVRF were significantly and positively associated to waist circumference and WHR, both in obese and in normal-weight subjects. In conclusion, not only obesity but also android fat in normal-weight subjects are important factors in cardiovascular disease even in the Mediterranean population, with a high intake of MUFA, where these factors seem to be more relevant to cardiovascular risk than dietary composition.     

二氢杨梅素对高脂饮食诱导的小鼠肥胖的影响及其机制

目的:观察二氢杨梅素(DHM)对高脂饮食诱导小鼠肥胖的影响,并探讨其作用机制是否与促进WAT棕色化有关。方法:60只c57bl/6j小鼠随机分为6组(n=10):①正常对照组(ND组):普通饲料喂养、②正常对照+低剂量DHM组(ND+L-DHM组):普通饲料喂养同时用低剂量DHM(125 mg/(kg·d))处理、③正常对照+高剂量DHM组(ND+H-DHM组):普通饲料喂养同时用高剂量DHM(250 mg/(kg·d))处理、④高脂饮食组(HFD):高脂饲料喂养、⑤高脂饮食+低剂量DHM组(HFD+L-DHM组):高脂饲料喂养同时用低剂量DHM处理、⑥高脂饮食+高剂量DHM组(HFD+H-DHM组):高脂饲料喂养同时用高剂量DHM处理。16周后小鼠空腹过夜,取血测空腹血糖和血脂,随后处死动物,测体长,算出Lee's指数;取肩胛下、腹股沟和附睾处脂肪组织称重后,甲醛固定、HE染色观察脂肪细胞大小,免疫组化检测解偶联蛋白1(UCP1)的表达;实验期间每4周测一次小鼠体重。结果:与ND组相比较,HFD组小鼠体重显著升高,提示肥胖小鼠模型复制成功。此外,HFD组小鼠体脂重量、脂肪细胞直径、Lee's指数和血糖显著增加、脂肪细胞UCP1的表达升高;使用L-DHM和H-DHM处理HFD小鼠后,体脂重量、脂肪细胞直径、Lee's指数和血糖等指标显著逆转,而脂肪细胞UCP1的表达升高更为显著;但L-DHM和H-DHM对正常小鼠上述指标无显著影响。结论:二氢杨梅素抑制高脂饮食诱导的小鼠肥胖,其机制可能与促进WAT棕色化有关。     

Genes, fat intake, and cardiovascular disease risk factors in the Quebec Family Study

Objective: The aim of this study was to assess gene‐diet interaction effects on cardiovascular disease (CVD) risk factors (waist circumference, plasma triacylglycerol, high‐density lipoprotein‐cholesterol and fasting glucose concentrations, and diastolic and systolic blood pressure) in the Quebec Family Study cohort. Design: Sixty‐four polymorphisms from 45 candidate genes were studied in 645 subjects. Dietary fat intake was obtained from a 3‐day weighted food record. Results: We observed 18 significant interactions at a p value ≤ 0.01. Among them, the Pro12Ala polymorphism in peroxisome proliferator‐activated receptor γ, alone or in interaction with fat intake, significantly modulated waist circumference (p = 0.0005 for both effects). Additionally, the apolipoprotein E genotype in interaction with fat intake was significantly associated with diastolic and systolic blood pressure (p = 0.01 and p = 0.001, respectively). The ghrelin Leu72Met polymorphism also interacted with dietary fat in its relation to waist circumference and triacylglycerol concentrations (p = 0.0004 and p = 0.005). Discussion: These results suggest that several alleles at candidate genes interact with dietary fat intake to modulate well‐known CVD risk factors. The identification of gene‐diet interaction effects is likely to provide useful information concerning the etiology of CVD.     

Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet

A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double-transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin- and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity.     

Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women

The individual response to diet may be influenced by gene polymorphisms. This study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713), ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate weight loss. The study was a seven weeks dietary weight loss intervention with Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated and polymorphisms in these genes were assessed by real-time PCR assays. Two-way repeated-measures ANOVA (2 × 2) were used to analyze the intervention effect between polymorphisms and BMI over the period and after stratification for age and socioeconomic status (SES). The weight loss intervention resulted in decreased BMI over the seven-week period (p < 0.001), for high and low SES (p < 0.05) and mainly for participants with 30–49 y. The intervention did not result in a statistically significant difference in weight loss between polymorphism carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower BMI compared to non-carriers in the low SES (p = 0.018) and the 30–39 y (p = 0.036) groups, suggesting a role for this polymorphism related to BMI control.     

Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos

Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity.     

Water relations in competitive interactions of Mediterranean grasses and shrubs

In Mediterranean ecosystems, competition between opportunistic grasses and slower-growing woody species may affect the speed and path of ecosystem recovery and the success of restoration plantings after natural or human-induced disturbance. In this experiment, competitive interactions between Mediterranean annual and perennial grass species (Avena fatua and Brachypodium retusum, respectively) and an important Mediterranean shrub (Rosmarinus offlcinalis) were examined under semi-controlled conditions simulating wet and dry Mediterranean rainfall regimes. The identity of the grass competitor and the level of water availability in the plots interacted to produce differing rates of R. offlcinalis growth but similar levels of mortality. In particular, competition with the perennial grass resulted in very low rates of R. offlcinalis growth at both irrigation levels. Measurements of soil water content showed that both grasses reduced soil moisture to low levels, though this effect was temporary in the case of the winter annual grass. Resistance to hydraulic flow in roots was highest in the perennial grass, smaller but of similar magnitude in the shrub, and much lower in the annual grass. Transpirational response to decreasing leaf water potential was a quick, sharp drop in conductance in R. offlcinalis, in contrast to a moderated decline from much lower initial transpiration rates in B. retusum. The annual grass largely maintained both leaf water potential and transpiration through leaf-tip senescence and death. Quantification of the rate of hydric recuperation of leaves after irrigation of drought-stressed plants showed that the perennial grass recovered at a rate four times that of R. offlcinalis, suggesting a strategy for making quick use of rare summer rains that may contribute to its competitive success. The appropriateness of planting or suppressing grasses in restoration of disturbed sites in Mediterranean Spain is discussed.     

Lifetime fecundity and floral variation in Tuberaria guttata (Cistaceae), a Mediterranean annual

In Tuberaria guttata, petal length, ovule number, and seeds per capsule raised steeply with increasing plant size (respectively, in the ranges 6-11 mm, 40-100, and 20-80), while the number of stamens varied relatively little (14-20). All flowers set fruit, and the rates of embryo abortion were independent of plant size and low on average. Individual fecundities had a markedly right-skewed frequency distribution (in the ranges 1-20 capsules and 20-1500 seeds per plant), which issued not only from plant size and flower production being positively correlated, but also from per-flower ovule numbers being directly proportional to plant size. Correlated variation of plant and ovary sizes amplified among-plant inequalities regarding fecundity; allowed larger plants to set ca. 50% more seed than expected on the basis of flower number only; and caused the slope of the size-fecundity relationship to be considerably steeper (at the population level) than if ovule number was a fixed trait. Corolla, ovary and androecium plasticity in Tuberaria are discussed in terms of environmental effects and developmental constraints.