The 2010 Dietary Guidelines for Americans (DGA) recommend nutrient needs be met by increasing fruit, vegetable, and whole-grain intake with the use of low-fat or fat-free dairy products and by ...reducing sodium, solid fats, and added sugars. However, the DGA, as a dietary pattern, have not been tested in an intervention trial.
The aim of this study was to evaluate the impact of a DGA-based diet compared with a representative typical American diet (TAD) on glucose homeostasis and fasting lipids in individuals at risk of cardiometabolic disease.
A randomized, double-blind, controlled 8-wk intervention was conducted in overweight and obese women selected according to indexes of insulin resistance or dyslipidemia. Women were randomly assigned to the DGA or TAD group (n = 28 DGA and 24 TAD). The TAD diet was based on average adult intake from the NHANES 2009–2010. The DGA and TAD diets had respective Healthy Eating Index scores of 98 and 62. All foods and beverages were provided during the intervention. Oral-glucose tolerance and fasting lipids were evaluated at 0, 2, and 8 wk of the intervention. Insulin resistance and sensitivity were estimated with the use of surrogates (e.g., homeostasis model assessment of insulin resistance).
By design, volunteers maintained their weight during the intervention. Fasting insulin, glucose, triglycerides, oral-glucose tolerance, and indexes of insulin resistance were not affected by either of the diets. Systolic blood pressure decreased in the DGA group (∼−9 mm Hg; P < 0.05). Total and HDL cholesterol also decreased in both groups (P < 0.05). Exploratory analysis comparing volunteers entering the study with insulin resistance and dyslipidemia with those with only dyslipidemia did not show an effect of pre-existing conditions on glucose tolerance or fasting lipid outcomes.
The consumption of a DGA dietary pattern for 8 wk without weight loss reduced systolic blood pressure. There were no differences between the DGA and TAD diets in fasting insulin, glucose, indexes of insulin resistance, or fasting lipids. This trial was registered at www.clinicaltrials.gov as NCT02298725.
Abstract only
Objective
To determine the associations between reported dairy consumption and indices of cardiovascular health.
Methods
33 women fitting pre‐metabolic syndrome criteria, mean age 46.9 ...y, mean BMI 32.5 kg/m
2
, were included in a 9‐week, free‐living, controlled‐feeding study. At baseline, the validated Block 2014 Food Frequency questionnaire (FFQ) was administered to determine habitual diet. Fasting blood was drawn to determine triglycerides (TG) and non‐HDL cholesterol (nHDL). The EndoPAT 2000, a non‐invasive finger plethysmography system, was used to measure cardiovascular functional parameters such as the reactive hyperemia index (RHI‐a measure of endothelial function), and augmentation index (AI – a measure of arterial stiffness). The AI was normalized to a 75 beats per minute heart rate across the volunteers to control for variation induced by differing heart rates (AI@75). Habitual intake of yogurt, milk, cheese, and total dairy (a summation of the aforementioned plus whey) in cup equivalents was obtained from the FFQ and used for this study. Spearman's non‐parametric correlation analysis was performed to evaluate associations between dairy intake and measured cardiovascular risk factors.
Results
Fasting TG was inversely associated with habitual consumption of yogurt (r = −0.561, p = 0.0007), milk (r = −0.438, p = 0.011), combined milk, yogurt and cheese (r = −0.37, p = 0.0342), and total dairy (r = −0.35, p = 0.046). Yogurt consumption was also inversely associated with nHDL (r = −0.376, p = 0.03). EndoPAT indices were also correlated with dairy consumption. Contrastingly, AI@75 was associated with yogurt consumption (r = 0.378, p = 0.03), and RHI was inversely associated with cheese consumption (r = −0.34, p = 0.053).
Conclusions
Elevated TG and nHDL are associated with cardiovascular disease, and their inverse association with dairy consumption suggests a likely beneficial effect of consuming dairy products, such as milk and yogurt. However, physiological measurements of cardiovascular function give contrasting results in terms of dairy's influence on cardiovascular health. Yogurt was also positively associated with AI@75, and cheese was inversely associated with RHI. Further dairy intervention studies are needed to confirm these relationships.
Support or Funding Information
National Dairy Council Project 23370; USDA‐ARS‐CRIS Project 2032‐51530‐022‐00D
Atherogenesis is an insipidus but precipitating process leading to serious consequences of many cardiovascular diseases (CVD). Numerous genetic loci contributing to atherosclerosis have been ...identified in human genome-wide association studies, but these studies have limitations in the ability to control environmental factors and to decipher cause/effect relationships. To assess the power of hyperlipidemic Diversity Outbred (DO) mice in facilitating quantitative trait loci (QTL) analysis of complex traits, we generated a high-resolution genetic panel of atherosclerosis susceptible (DO-F1) mouse cohort by crossing 200 DO females with C57BL/6J males carrying two human genes: encoding apolipoprotein E3-Leiden and cholesterol ester transfer protein. We examined atherosclerotic traits including plasma lipids and glucose in the 235 female and 226 male progeny before and after 16 weeks of a high-fat/cholesterol diet, and aortic plaque size at 24 weeks. We also assessed the liver transcriptome using RNA-sequencing. Our QTL mapping for atherosclerotic traits identified one previously reported female-specific QTL on Chr10 with a narrower interval of 22.73 to 30.80 Mb, and one novel male-specific QTL at 31.89 to 40.25 Mb on Chr19. Liver transcription levels of several genes within each QTL were highly correlated with the atherogenic traits. A majority of these candidates have already known atherogenic potential in humans and/or mice, but integrative QTL, eQTL, and correlation analyses further pointed Ptprk as a major candidate of the Chr10 QTL, while Pten and Cyp2c67 of the Chr19 QTL in our DO-F1 cohort. Finally, through additional analyses of RNA-seq data we identified genetic regulation of hepatic transcription factors, including Nr1h3, contributes to atherogenesis in this cohort. Thus, an integrative approach using DO-F1 mice effectively validates the influence of genetic factors on atherosclerosis in DO mice and suggests an opportunity to discover therapeutics in the setting of hyperlipidemia.
Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC ...concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney gene expression to determine if the gene modules with common functions are associated with kidney biomarkers of chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levels of CysC are associated with genetic variation and are transcriptionally coregulated by immune genes. Specifically, Type-I interferon signaling genes are coexpressed with
mRNA levels and associated with CysC concentrations in plasma. Our findings demonstrate the complex control of CysC by genetic polymorphisms and inflammatory pathways.
Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression ...quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation (
or
) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a
-acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general,
-acting variants affecting mRNA or miRNA expression explain more phenotypic variance than
-acting variants. Lastly, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility.
Abstract
Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting ...expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation (cis or trans) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a trans-acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general, cis-acting variants affecting mRNA or miRNA expression explain more phenotypic variance than trans-acting variants. Finally, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility
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BMI is a widely used anthropometric measure for identifying CVD and metabolic syndrome (MetS) risk. Two new anthropometric indices are A Body Shape Index (ABSI) and Body Roundness Index ...(BRI) that may provide better correlations to features of MetS.
Methods
Subject data were obtained from 91 overweight or obese (BMI 31.8 kg/m2 ± 3.7) women who screened for participation in a dietary pattern intervention study (NCT02298725). The screening consisted of collecting anthropometric, blood biomarker, and blood pressure measures. The screening measures were performed to identify participants who have metabolic syndrome.
Results
Ninety one participants were successfully screened for symptoms of metabolic syndrome. Three anthropometric indices, BMI, ABSI, and BRI, were used to find correlations with clinical measures of MetS. Fasting OGTT Glucose (FG), Two Hour OGTT Glucose (Gluc‐2Hr), Hemoglobin A1c (HbA1C), and Quantitative Insulin Sensitivity Check Index (QUICKI) did not significantly correlate with any of these indices. All of these indices had a significant correlation with Triglyceride (TG) and log HOMA (Homeostatic Model Assessment). BRI and BMI had high correlations with several blood measures that are indicative of MetS.
Out of the anthropometric indices studied, BRI was significantly correlated with TG (r=0.362), HDL (r=−0.418) and HOMA (r=0.303). BMI was significantly correlated with HOMA (r=0.400), log HOMA (r=0.405), and the Matsuda Index (r=−0.255). Although demonstrating significant correlations with several measures, ABSI had weaker correlations than both BRI and BMI in all cases.
It is also of note that there is significant difference between the mean ABSI of participants who had one or less, two, or three or more primary parameters of MetS (p=0.0008). Similarly, the mean BRI of participants in these MetS groups were also different (p<0.001).
Conclusion
In general, BRI showed a stronger relationship to dyslipidemic measures while BMI showed a stronger relationship to glucose intolerance. Both ABSI and BRI showed significant differences between participants who had ≤1 feature of MetS and those who had ≥3 features of MetS, suggesting a potential role of ABSI and BRI as anthropometric indices for predicting MetS. With our next 100 screened participants we will be using these indices to validate these relationships.
Support or Funding Information
National Dairy Council and USDA project #2032‐51530‐022.
Abstract only
Objective
Dietary intake of added sugars in the United States is significantly higher than what is recommended by the Dietary Guidelines for Americans (DGA) and by other health ...organizations. There is limited research on how reducing the intake of added sugars would affect or change taste perception related to sugar. Our objective was to determine if sweet taste threshold and sweet preference changes in response to a diet intervention based on the recommendations in the 2010 DGA compared to an intervention based on the typical American diet (TAD) as described by recent surveys of U.S. adults.
Methods
Data for this report is from an eight‐week controlled feeding trial. Overweight or obese women, with insulin resistance and/or dyslipidemia, aged 20–65 years were randomized into one of two diet groups: the DGA diet or the TAD. Detection taste threshold was determined using a three‐alternative‐forced choice method and sweet preference was measured using the Monell forced‐choice, paired‐comparison tracking procedure. Measurements were obtained prior to the dietary intervention at baseline (BL), and after the diet intervention (ADI) to evaluate changes in taste acuity and hedonic preference. Data were log transformed, and analysis of covariance was used to identify differences between the two diet groups. In addition, the change in acuity and hedonic preference was calculated as ADI‐BL. Wilcoxon's rank test was used to identify differences in these parameters between the two groups. This is an on‐going study, with more participant cohorts being added to reach n = 44.
Results
Preliminary results were generated for the first 16 women (Age: DGA ‐ 45.0, TAD‐42.5 y; BMI: DGA – 30.4, TAD – 33.0 kg/m
2
) who have completed the study. Usual energy intake (kcals), and percent‐added sugars or sweet‐food intake were not different at BL between DGA and TAD (p = 0.92, 0.63, 0.92, respectively). There was no significant difference (p > 0.05) between diets in the change in sweet threshold or sweet preference. The DGA intervention, however, resulted in a larger reduction in the level of preferred sweetness compared to the TAD diet, when controlling for BL preference (p = 0.03).
Conclusions
Consuming a diet following the DGA may possibly lower preference for sweet foods when compared to a TAD. Further, data from the complete cohort will be used to add to this report upon study completion.
Support or Funding Information
Funded by National Dairy Council and USDA, ARS CRIS project #2032 51530 022 00D
Abstract only
Objective
The primary aim was to assess metabolic flexibility as it relates to habitual diet, as well as in response to a high fat meal challenge (HFMC).
Methods
Thirty‐three women with ...insulin resistance and/or dyslipidemia were enrolled in this study. Block food frequency 2014 questionnaire was used to evaluate habitual dietary patterns. A HFMC test (800 kcal, 60% fat, 25% cho, 15% pro) was provided in a protocol that included blood sampling and measures of O
2
and CO
2
exchange using a metabolic cart at fasting and at 30, 180 and 360 minutes postprandial. Metabolic rate (MR), respiratory exchange ratio (RER), fat (FOx) and carbohydrate (COx) oxidation rates were calculated from metabolic cart data. Food quotients (FQ) for habitual diets and the HFMC were calculated. Metabolic flexibility was assessed in the fasted state by comparing the FQ of the habitual diet with fasting RER (FQ
DIET
/RER
f
). In the postprandial state, metabolic flexibility was defined as a ratio of difference between average postprandial FOx and fasting FOx/difference between average postprandial COx and fasting COx (ΔFOx/ΔCOx) and also the HFMC‐FQ compared to postprandial RER (FQ
HFMC
/RER
HFMC
). Higher values for FQ
DIET
/RER
f
, ΔFOx/ΔCOx, and FQ
HFMC
/RER
HFMC
indicate higher FOx relative to COx. Spearman's correlation analysis was used to evaluate associations between dietary variables and metabolic flexibility.
Results
Three women were outliers (with reported dietary intake > 4000 Kcal/d), and the remaining 30 women were included for analysis. ΔFOx/ΔCOx was inversely associated with resting MR (r = −0.444, p =0.010), and showed an inverse trend with omega‐3 fatty acid 20:4 (r = −0.33, p = 0.07). FQ
DIET
/RER
f
similar to ΔFOx/ΔCox, showed an inverse trend with omega‐3 fatty acid 20:5 and 22:6 intakes (r = −0.31, p = 0.09, r = −0.33, p = 0.07). Similarly, FQ
HFMC
/RER
HFMC
also showed an inverse trend with 20:5 and 22:6 (r = −0.33, p = 0.07 for both). It is of interest to note that while both FQ
DIET
/RER
f
and FQ
HFMC
/RER
HFMC
were positively associated with habitual caffeine intake (r = 0.53, p<0.01, r = 0.39, p = 0.03), ΔFOx/ΔCOx was not (r =−0.15, p = 0.43). Also, both FQ
DIET
/RER
f
and FQ
HFMC
/RER
HFMC
were positively associated with habitual intake of flavanones (r = 0.37, p = 0.05; r = 0.35, p = 0.06), specifically hesperetin intake (r = 0.41, p = 0.03; r = 0.38, p = 0.04).
Conclusions
Metabolic flexibility based on fasting measures was associated with lower intake of some long chain omega‐3 fatty acids, and higher intake of caffeine and flavanones in women. Higher intakes of omega‐3 fatty acids also indicated poorer adaptation to the HFMC. However, these must be tested in a larger sample size, as well as in a controlled feeding trial.
Support or Funding Information
National Dairy Council Project 23370, and USDA‐ARS‐CRIS Project 2032‐51530‐022‐00D
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