Effects of a diet based on the Dietary Guidelines on vascular health and TMAO in women with cardiometabolic risk factors.

BACKGROUND AND AIMS: Recent evidence links trimethylamine oxide (TMAO) to endothelial dysfunction, an early indicator of cardiovascular disease. We aimed to determine whether short-term consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA) would affect endothelial function, plasma TMAO concentrations, and cardiovascular disease risk, differently than a typical American Diet (TAD). METHODS AND RESULTS: An 8-wk controlled feeding trial was conducted in overweight/obese women pre-screened for insulin resistance and/or dyslipidemia. Women were randomized to a DGA or TAD group (n = 22/group). At wk0 (pre-intervention) and wk8 (post-intervention) vascular age was calculated; endothelial function (reactive hyperemia index (RHI)) and augmentation index (AI@75) were measured using EndoPAT, and plasma TMAO was measured by LC-MS/MS. Vascular age was reduced in DGA at wk8 compared to wk0 but TAD wk8 was not different from wk0 (DGA wk0: 54.2 ± 4.0 vs. wk8: 50.5 ± 3.1 (p = 0.05), vs. TAD wk8: 47.7 ± 2.3). Plasma TMAO concentrations, RHI, and AI@75 were not different between groups or weeks. CONCLUSION: Consumption of a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO. CLINICALTRIALS.GOV: NCT02298725.

Resistant starch wheat increases PYY and decreases GIP but has no effect on self-reported perceptions of satiety.

Dietary fiber has numerous health benefits, such as increasing satiety, and is regularly included in healthy dietary recommendations. However, different types and sources of fiber vary in their chemical properties and biological effects. This double-blind, randomized, placebo-controlled, crossover study investigated the effects of resistant starch type 2 (RS2) from wheat on self-reported perceptions of satiety and associated gut hormones in 30 healthy adults ages 40-65 years of age. Participants consumed rolls made using either RS2-enriched wheat flour or a wild-type flour for one week before a test day during which they ate a mixed meal containing the same roll type. Both self-reported perceptions of satiety and plasma concentrations of gut hormones were measured following the meal to assess whether the RS2-enriched wheat enhanced satiety and suppressed hunger for a longer period than the control wheat. Exploratory analysis indicated that fasting and peak concentration of peptide YY3-36 (PYY3-36; qfast = 0.02, qpeak = 0.02) increased, while peak concentration and iAUC of glucose-dependent insulinotropic peptide (GIP; qpeak < 0.001, qiAUC < 0.001) decreased after ingesting RS2-enriched wheat. However, self-reported perceptions of hunger or fullness using visual analog scales (VAS) did not differ following the test meal.

Technician-Scored Stool Consistency Spans the Full Range of the Bristol Scale in a Healthy US Population and Differs by Diet and Chronic Stress Load.

BACKGROUND: Prior studies of adults with constipation or diarrhea suggest that dietary intake, physical activity, and stress may affect stool consistency. However, the influence of these factors is unresolved and has not been investigated in healthy adults. OBJECTIVES: We assessed the relations of technician-scored stool consistency in healthy adults with self-reported diet, objectively monitored physical activity, and quantifiable markers of stress. METHODS: Stool consistency was scored by an independent technician using the Bristol Stool Form Scale (BSFS) to analyze samples provided by healthy adults, aged 18-65 y, BMI 18-44 kg/m2, in the USDA Nutritional Phenotyping Study (n = 364). A subset of participants (n = 109) were also asked to rate their sample using the BSFS. Dietary intake was assessed with two to three 24-h recalls completed at home and energy expenditure from physical activity was monitored using an accelerometer in the 7-d period preceding the stool collection. Stress was measured using the Wheaton Chronic Stress Inventory and allostatic load (AL). Statistical and machine learning analyses were conducted to determine which dietary, physiological, lifestyle, and stress factors differed by stool form. RESULTS: Technician-scored BSFS scores were significantly further (P = 0.003) from the central score (mean ± SEM distance: 1.41 ± 0.089) than the self-reported score (1.06 ± 0.086). Hard stool was associated with higher (P = 0.005) intake of saturated fat (13.8 ± 0.40 g/1000 kcal) than was normal stool (12.5 ± 0.30 g/1000 kcal). AL scores were lower for normal stool (2.49 ± 0.15) than for hard (3.07 ± 0.18) (P = 0.009) or soft stool (2.89 ± 0.18) (P = 0.049). Machine learning analyses revealed that various dietary components, physiological characteristics, and stress hormones predicted stool consistency. CONCLUSIONS: Technician-scored stool consistency differed by dietary intake and stress hormones, but not by physical activity, in healthy adults.This trial was registered at clincialtrials.gov as NCT02367287.

Weight Loss, but Not Dairy Composition of Diet, Moderately Affects Satiety and Postprandial Gut Hormone Patterns in Adults.

BACKGROUND: Inclusion of dairy in diet patterns has been shown to have mixed effects on weight loss. A prevailing hypothesis is that dairy improves weight loss by influencing endocrine systems associated with satiety and food intake regulation. OBJECTIVES: The objective of the current study was to evaluate the effect of weight loss with or without adequate dietary dairy on subjective and objective appetitive measures. METHODS: Men and women who were habitual low dairy consumers (n = 65, 20-50 y) participated in a 12-wk randomized controlled feeding weight loss trial. During the 12-wk intervention, a low-dairy (<1 serving dairy/d) was compared with an adequate-dairy (3-4 servings dairy/d) diet, both with a 500-kcal deficit/d. Test days, before and at the end of the intervention, began with 2 fasting blood draws and visual analog scale (VAS) measures, followed by a standard breakfast (25% of prescribed restricted calories), 5 postbreakfast blood draws and VASs, a standard lunch (40% of restricted energy amount), and 12 postlunch blood draws and VASs. Blood samples were used for satiety hormone measurements. On a separate day when matching standard meals were consumed, an ad libitum buffet meal was provided as dinner, at a self-selected time. Meal duration and intermeal interval were recorded. RESULTS: Weight loss (-6.1 kg), irrespective of dairy, resulted in reduced fasting insulin (-20%) and leptin (-25%), and increased fasting acylated ghrelin (+25%) and VAS desire to eat (+18%) (P < 0.05). There were no effects of dairy on objective or subjective satiety measures. Weight loss marginally reduced the intermeal interval (289 min compared with 276 min, P = 0.059) between lunch and the ad libitum buffet. CONCLUSIONS: These results do not support the hypothesis that inclusion of dairy in long-term dietary patterns influences appetite during weight loss. Weight loss per se has a modest impact on select systems that regulate hunger and satiety.This trial was registered at clinicaltrials.gov as NCT00858312.

Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease.

BACKGROUND: Glycoproteomics deals with glycoproteins that are formed by post-translational modification when sugars (like fucose and sialic acid) are attached to protein. Glycosylation of proteins influences function, but whether glycosylation is altered by diet is unknown. OBJECTIVE: To evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating glycoproteins that have previously been associated with cardiometabolic diseases. DESIGN: Forty-four women, with one or more metabolic syndrome characteristics, completed an 8-week randomized controlled feeding intervention (n = 22) consuming a diet based on the Dietary Guidelines for Americans (DGA 2010); the remaining consumed a 'typical American diet' (TAD, n = 22). Fasting serum samples were obtained at week0 (baseline) and week8 (post-intervention); 17 serum proteins were chosen for targeted analyses. Protein standards and serum samples were analyzed in a UHPLC-MS protocol to determine peptide concentration and their glycan (fucosylation or sialylation) profiles. Data at baseline were used in correlational analyses; change in proteins and glycans following intervention were used in non-parametric analyses. RESULTS: At baseline, women with more metabolic syndrome characteristics had more fucosylation (total di-fucosylated proteins: p = 0.045) compared to women with a lesser number of metabolic syndrome characteristics. Dietary refined grain intake was associated with increased total fucosylation (ρ = - 0.530, p < 0.001) and reduced total sialylation (ρ = 0.311, p = 0.042). After the 8-week intervention, there was higher sialylation following the DGA diet (Total di-sialylated protein p = 0.018, poly-sialylated orosomucoid p = 0.012) compared to the TAD diet. CONCLUSIONS: Based on this study, glycosylation of proteins is likely affected by dietary patterns; higher sialylation was associated with a healthier diet pattern. Altered glycosylation is associated with several diseases, particularly cancer and type 2 diabetes, and this study raises the possibility that diet may influence disease state by altering glycosylation. CLINICAL TRIAL REGISTRATION: NCT02298725 at clinicaltrials.gov; https://clinicaltrials.gov/ct2/show/NCT02298725 .

Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention.

Insulin resistance has wide-ranging effects on metabolism, but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ∼45% of V̇o2peak, ∼63 W) and recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ∼14-wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise, regardless of pre- versus postintervention status, highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of nonoxidative fates of glucose [e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside (possible glycerolipid synthesis metabolite)], and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites ("non-self" molecules, from microbes or foods), including benzoic acid-salicylic acid-salicylaldehyde, hexadecanol-octadecanol-dodecanol, and chlorogenic acid. In addition, many nonannotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results and previously reported plasma acylcarnitine profiles support the principle that most metabolic changes during submaximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.

Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII, and ApoE in humans consuming a high-fructose corn syrup-sweetened beverage.

Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages increases risk factors involved in the development of obesity, Type 2 diabetes, and cardiovascular disease (CVD). Our previous study demonstrated that when compared with aspartame (Asp), 2 wk of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl- sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS- or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS- or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA, and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA vs. ppTG, ppApoCIII, and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS consumption.

A Clear Difference Emerges in Hormone Patterns Following a Standard Midday Meal in Young Women Who Regularly Eat or Skip Breakfast.

BACKGROUND: Multiple hormones are involved in the regulation of food intake and glucose metabolism. Past intervention studies showed a benefit of eating breakfast on satiety, but this was possibly confounded by the disruption of habitual meal patterns. OBJECTIVE: The objective of this study was to compare hormonal responses, including insulin, leptin, glucagon-like peptide-1, ghrelin, peptide YY (PYY3-36), and cholecystokinin (CCK), between habitual breakfast eaters (Br-Es) and habitual skippers (Br-Ss) to a standard midday meal. METHODS: Thirty-two women [mean ± SD age: 22.6 ± 3.3 y; body mass index (in kg/m2): 21.8 ± 2.0] participated in a cross-sectional study that consisted of a 3-h test protocol that included a standard test meal served at 1230 with pre- and postmeal blood sampling. The protocol required that Br-Es eat a typical breakfast between 0700 and 1000, whereas Br-Ss had no breakfast meal and had fasted for 12 h. Blood was drawn 35 and 5 min prelunch and 5, 20, 35, 50, and 110 min postlunch. RESULTS: Repeated-measures ANOVA revealed a group difference for PYY3-36 (P = 0.001), with the Br-E group exhibiting 50-90% higher concentrations throughout the test period. Leptin tended to be different (P = 0.08) between groups, with higher mean ± SD values for the Br-S group (27.6 ± 29.6 ng/mL) compared with the Br-E group (11.5 ± 9.8 ng/mL). Partial least squares regression analysis confirmed that these 2 hormones were important contributors to the patterns of the hormones, anthropometric, clinical, and behavioral variables that differed between groups; insulin and CCK were important as well. CONCLUSION: We found differences between the Br-E and Br-S groups in circulating gut and adipose-derived hormones measured midday, indicating that the breakfast habit is associated with the hormonal milieu before and after a midday meal. The different patterns may be short-lived or may impact metabolism later in the day. This report is a secondary analysis of a trial registered at clinicaltrials.gov as NCT01427556.

Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

NEW FINDINGS: What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. With insulin resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives [markers of incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle ß-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 µm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain.

Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction.

BACKGROUND: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation. OBJECTIVE: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity. METHODS: Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders. RESULTS: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P = 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01]. CONCLUSIONS: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312.

Effects of Consuming Beverages Sweetened with Fructose, Glucose, High-Fructose Corn Syrup, Sucrose, or Aspartame on OGTT-Derived Indices of Insulin Sensitivity in Young Adults.

(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.

Dairy food consumption and meal-induced cortisol response interacted to influence weight loss in overweight women undergoing a 12-week, meal-controlled, weight loss intervention.

Dairy food enhances weight loss in animal models, possibly by modifying the metabolic effects of cortisol. This study determined in overweight women (ages 20.0-45.9 y; n = 51) whether including dairy food in an energy-restricted diet affects cortisol concentrations and whether differences in provoked cortisol explain the magnitude of weight loss. Women received either an adequate amount of dairy food (AD), the equivalent of ≥711 mL/d milk, or a low amount of dairy food (LD), the equivalent to ≤238 mL/d milk, in a 12-wk, energy-restricted dietary intervention. Participants were tested in a 12-h laboratory visit, which included 2 standard meals and a dinner buffet that was consumed ad libitum. Salivary cortisol was measured from waking to bedtime. Energy restriction increased (P ≤ 0.04) the minimum and decreased (P ≤ 0.02) the diurnal amplitude in the salivary cortisol concentration from baseline to postintervention. Energy restriction enhanced the dinner meal-stimulated salivary cortisol response (DMR) (P ≤ 0.02) but only in the LD group. Compared with the LD treatment, the AD treatment induced (P ≤ 0.04) greater reductions in body weight and fat, but only in women characterized as having a baseline DMR (responders) (n = 26); weight and fat lost in the AD and LD groups were similar in nonresponders (n = 25). Overall, energy restriction dampened diurnal salivary cortisol fluctuations [symptomatic of hypothalamic-pituitary-adrenal (HPA) axis dysfunction] and enhanced dinner meal-stimulated salivary cortisol concentrations. The AD treatment prevented the latter. Furthermore, certain phenotypic markers of HPA axis function may help to expose the weight-reducing effects of consuming dairy food.

A Diet Pattern Characterized by Sugar-Sweetened Beverages Is Associated with Lower Decision-Making Performance in the Iowa Gambling Task, Elevated Stress Exposure, and Altered Autonomic Nervous System Reactivity in Men and Women.

The executive brain mediates and facilitates a set of cognitive functions, such as decision making, planning, self-regulation, emotional regulation, and attention. Executive dysfunction and related diseases are a rising public health concern. Evidence supports a link between nutritional factors and executive function (EF), but relatively little information exists about the relationship between diet patterns and this higher order cognitive ability. We and others have reported on the relationships between body weight regulation and affective decision making, as measured by performance in the Iowa Gambling Task (IGT). However, little is known about the relationships between performance in this decision-making task and whole diet patterns. In this study, we tested whether data-derived diet patterns based on energy-adjusted food intake data from the Block Food Frequency Questionnaire were associated with decision-making performance in the IGT. Secondarily, we examined the influence of these diet patterns on self-reported chronic stress exposure and heart rate variability, which is a marker of autonomic nervous system (ANS) activity. In prior studies, stress and ANS activity were shown to influence decision-making performance in the IGT. In this study, five distinct diet patterns were identified by cluster and factor analyses. A diet pattern best characterized by elevated sugar-sweetened beverage and added sugar consumption was associated with the lowest decision-making performance (p = 0.0049) and higher stress exposure (p = 0.0097). This same diet pattern was associated (p = 0.0374) with an IGT-affiliated decline in high-frequency HRV and an increase in low-frequency HRV, suggesting diet-induced ANS regulatory shifts in response to performing the EF task. Compared to the sugar-sweetened beverage diet pattern, diet patterns defined by more fruits/vegetables and low red meat (p = 0.0048) or higher omega-3 fatty acids and seafood (p = 0.0029) consumption were associated with lower chronic stress exposure. All outcomes were statistically adjusted for differences in BMI, age, sex, education level, and sensorimotor ability. Our findings provide new information that further supports the potential importance of whole diet patterns on cognitive disease prevention.

An Intervention of Four Weeks of Time-Restricted Eating (16/8) in Male Long-Distance Runners Does Not Affect Cardiometabolic Risk Factors.

Timing of nutrient intake for athletes may affect exercise performance and cardiometabolic factors. Our objective was to examine the effect of time-restricted eating (TRE) on cardiometabolic health. Using a cross-over study design, 15 endurance-trained male runners were randomized to either a normal dietary pattern (ND) first (12 h eating/fasting times) followed by time-restricted eating (TRE) pattern (16 h fast; 8 h eating) or the reverse, with a 4-week washout period between interventions. Body composition, resting energy expenditure, blood pressure and serum insulin, glucose and lipids were measured using standard laboratory methods. Exercise training and dietary intake (calories and macronutrients) were similar across interventions. No significant differences were observed in resting energy expenditure, markers of insulin resistance, serum lipids or blood pressure. Body composition did change significantly (p < 0.05) with whole body fat mass (-0.8 ± 1.3 kg with TRE vs. +0.1 ± 4.3 kg with ND), leg fat mass (-0.3 ± 0.5 kg with TRE vs. +0.1 ± 0.4 kg with ND), and percent body fat (-1.0 ± 1.5% with TRE vs. +0.1 ± 1.3% with ND) declining more in the TRE intervention, with no change in fat-free mass. This study is one of a few to investigate the effects of an isocaloric 16/8 TRE eating pattern in trained endurance athletes and confirms no change in cardiometabolic risk factors. In conclusion, TRE is not detrimental to cardiometabolic health in endurance-trained male runners but could be beneficial on exercise performance by reducing fat mass.

Effects of a genetic variant rs13266634 in the zinc transporter 8 gene (SLC30A8) on insulin and lipid levels before and after a high-fat mixed macronutrient tolerance test in U.S. adults.

BACKGROUND: The common C-allele of rs13266634 (c.973C>T or p.Arg325Trp) in SLC30A8 (ZNT8) is associated with increased risk of type 2 diabetes. While previous studies have examined the correlation of the variant with insulin and glucose metabolism, the effects of this variant on insulin and lipid responses after a lipid challenge in humans remain elusive. The goal of this study was to determine whether the C-allele had an impact on an individual's risk to metabolic syndromes in U.S. adults. METHOD: We studied the genotypes of rs13266634 in 349 individuals aged between 18 and 65 y with BMI ranging from 18.5 to 45 kg/m2. The subjects were evaluated for insulin, glucose, HbA1c, ghrelin, and lipid profiles before and after a high-fat mixed macronutrient tolerance test (MMTT). RESULTS: We found that the effects of variants rs13266634 on glucose and lipid metabolism were sex-dimorphic, greater impact on males than on females. Insulin incremental area under the curve (AUC) after MMTT was significantly decreased in men with the CC genotype (p < 0.05). Men with the CC genotype also had the lowest fasting non-esterified fatty acid (NEFA) concentrations. On the other hand, the TT genotype was associated with a slower triglyceride removal from the circulation in men after MMTT. The reduced triglyceride removal was also observed in subjects with BMI ≥ 30 carrying either the heterozygous or homozygous T-allele. Nevertheless, the SNP had little effect on fasting or postprandial blood glucose and cholesterol concentrations. CONCLUSION: We conclude that the CC genotype negatively affects insulin response after MMTT while the T-allele may negatively influence lipolysis during fasting and postprandial blood triglyceride removal in men and obese subjects, a novel finding in this study.

Obesity Risk Assessment for Spanish-Speaking Immigrant Families with Young Children in the United States: Reliability and Validity with Nutrient Values.

The purpose is to examine validity and reliability for an obesity risk assessment tool developed in Spanish for immigrant families with children, 3-5 years old using an 8-week cross-sectional design with data collected over 1 year at Head Start and Special Supplemental Nutrition Program for Women, Infants and Children [WIC]. Parent/child dyads (206) provided a child obesity risk assessment, three child modified 24 h dietary recalls, three child 36+ h activity logs and one parent food behavior checklist. Main outcome measures were convergent validity with nutrients, cup equivalents, and diet quality and three assessments of reliability that included item difficulty index, item discrimination index, and coefficient of variation. Validity was demonstrated for assessment tool, named Niños Sanos. Scales were significantly related to variables in direction hypothesized [p ≤ 0.05]: Healthy Eating Index, fruit/vegetable cup equivalents, folate, dairy cup equivalents, vitamins D, ß-carotene, fiber, saturated fat, sugar, time at screen/ sleep/physical activity and parent behaviors. Three measures of reliability were acceptable. The addition of nutrient values as an analytical validation approach adds strength and consistency to previously reported Niños Sanos validation results using children's blood biomarkers and body mass index. This tool can be used by health professionals as an assessment of obesity risk in several capacities: (1) screener for counseling in a clinic, (2) large survey, (3) guide for participant goal setting and tailoring interventions, and (4) evaluation.

Waking Salivary Cortisol Associated with Magnitude of Cholesterol Reduction in Women Fed a Healthy Whole-Food Diet for 8 Weeks.

Background: Diet and cortisol are independently linked to cardiometabolic function and health, but underlying alterations in circulating cortisol may influence beneficial cardiometabolic effects of consuming a healthy diet. Objective: This study was a secondary analysis to examine whether baseline concentrations of waking salivary cortisol interacted with 8-wk whole-food diet interventions to affect cardiometabolic outcomes. Methods: A randomized, double-blind, controlled 8-wk diet intervention was conducted in 44 participants. The trial was conducted at the Western Human Nutrition Research Center in Davis, California. Participants were overweight or obese women aged 20-64 y, minimally active, and insulin resistant and/or dyslipidemic. Diets were randomly assigned and based on the 2010 Dietary Guidelines for Americans (DGA) or a typical American diet (TAD). Cardiometabolic risk factors and salivary cortisol were assessed at baseline and at 8 wk. Primary outcome measures included 8-wk change in overnight fasted cardiometabolic risk factors, including blood pressure, BMI, and circulating triglycerides, cholesterol, glycated hemoglobin (HbA1c), nonesterified fatty acids, and high-sensitivity C-reactive protein. This trial was approved by the University of California, Davis, Institutional Review Board. Results: Baseline waking cortisol concentrations interacted (P = 0.0474) with diet to affect 8-wk changes in fasting total cholesterol. Compared with a TAD, a DGA diet was associated with 8-wk decreases in total cholesterol in participants with low (10th percentile of all participants; 2.76 nmol/L) or average (7.76 nmol/L) but not higher (90th percentile of all participants; 13.44 nmol/L) baseline waking cortisol. Consistent with this finding, there was a DGA-specific positive association (P = 0.0047; b: 2.88 ± 0.94) between baseline waking cortisol and 8-wk increases in total cholesterol. Conclusions: The underlying status of waking cortisol may explain interindividual variability in total cholesterol responses to whole-food diets. This trial was registered at www.clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02298725) as NCT02298725.

Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test.

The use of meal challenge tests to assess postprandial responses in carbohydrate and fat metabolism is well established in clinical nutrition research. However, challenge meal compositions and protocols remain a variable. Here, we validated a mixed macronutrient tolerance test (MMTT), containing 56-g palm oil, 59-g sucrose, and 26-g egg white protein for the parallel determination of insulin sensitivity and postprandial triglyceridemia in clinically healthy subjects. The MMTT was administered in two study populations. In one, women with overweight/obese BMIs (n = 43) involved in an 8-week dietary intervention were administered oral glucose tolerance tests (OGTTs) and MMTTs within 2 days of each other after 0, 2, and 8 weeks of the dietary intervention. In the other, 340 men and women between 18 and 64 years of age, with BMI from 18-40 kg/m2, completed the MMTT as part of a broad nutritional phenotyping effort. Postprandial blood collected at 0, 0.5, 3, and 6 h was used to measure glucose, insulin, and clinical lipid panels. The MMTT postprandial insulin-dependent glucose disposal was evaluated by using the Matsuda Index algorithm and the 0- and 3 h blood insulin and glucose measures. The resulting MMTT insulin sensitivity index (ISIMMTT) was strongly correlated (r = 0.77, p < 0.001) with the OGTT-dependent 2 h composite Matsuda index (ISIComposite), being related by the following equation: Log (ISIComposite) = [0.8751 x Log(ISIMMTT)] -0.2115. An area under the triglyceride excursion curve >11.15 mg/mL h-1 calculated from the 0, 3, and 6 h blood draws established mild-to-moderate triglyceridemia in agreement with ∼20% greater prevalence of hypertriglyceridemia than fasting indications. We also demonstrated that the product of the 0 to 3 h and 3 to 6 h triglyceride rate of change as a function of the triglyceride incremental area under the curve optimally stratified subjects by postprandial response patterns. Notably, ∼2% of the population showed minimal triglyceride appearance by 6 h, while ∼25% had increasing triglycerides through 6 h. Ultimately, using three blood draws, the MMTT allowed for the simultaneous determination of insulin sensitivity and postprandial triglyceridemia in individuals without clinically diagnosed disease. Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT02298725; NCT02367287].

The Omega-3 Index Response to an 8 Week Randomized Intervention Containing Three Fatty Fish Meals Per Week Is Influenced by Adiposity in Overweight to Obese Women.

BACKGROUND: The Dietary Guidelines for Americans (DGA) recommends consuming ~225 g/wk of a variety of seafood providing >1.75 g/wk of long-chain omega-3 fatty acids to reduce cardiovascular disease risk, however individual responses to treatment vary. OBJECTIVE: This study had three main objectives. First, to determine if a DGA-conforming diet (DGAD), in comparison to a typical American diet (TAD), can increase the omega-3 index (OM3I), i.e., the red blood cell mol% of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA). Second, to identify factors explaining variability in the OM3I response to dietary treatment. Third to identify factors associated with the baseline OM3I. DESIGN: This is a secondary analysis of a randomized, double-blind 8 wk dietary intervention of overweight/obese women fed an 8d rotating TAD (n = 20) or DGAD (n = 22) registered at www.clinicaltrials.gov as NCT02298725. The DGAD-group consumed 240 g/wk of Atlantic farmed salmon and albacore tuna in three meals with an estimated EPA + DHA of 3.7 ± 0.6 g/wk. The TAD-group consumed ~160 g/wk of farmed white shrimp and a seafood salad containing imitation crab in three meal with an estimated EPA + DHA of 0.45 ± 0.05 g/wk. Habitual diet was determined at baseline, and body composition was determined at 0 and 8wks. Red blood cell fatty acids were measured at 0, 2 and 8 wk. RESULTS: At 8 wk, the TAD-group OM3I was unchanged (5.90 ± 1.35-5.80 ± 0.76%), while the DGAD-group OM3I increased (5.63 ± 1.27-7.33 ± 1.36%; p < 0.001). In the DGAD-group 9 of 22 participants achieved an OM3I >8%. Together, body composition and the baseline OM3I explained 83% of the response to treatment variability. Baseline OM3I (5.8 ± 1.3%; n = 42) was negatively correlated to the android fat mass (p = 0.0007) and positively correlated to the FFQ estimated habitual (EPA+DHA) when expressed as a ratio to total dietary fat (p = 0.006). CONCLUSIONS: An 8 wk TAD did not change the OM3I of ~6%, while a DGAD with 240 g/wk of salmon and albacore tuna increased the OM3I. Body fat distribution and basal omega-3 status are primary factors influencing the OM3I response to dietary intake in overweight/obese women.

Satiety Associated with Calorie Restriction and Time-Restricted Feeding: Central Neuroendocrine Integration.

This review focuses on summarizing current knowledge on how time-restricted feeding (TRF) and continuous caloric restriction (CR) affect central neuroendocrine systems involved in regulating satiety. Several interconnected regions of the hypothalamus, brainstem, and cortical areas of the brain are involved in the regulation of satiety. Following CR and TRF, the increase in hunger and reduction in satiety signals of the melanocortin system [neuropeptide Y (NPY), proopiomelanocortin (POMC), and agouti-related peptide (AgRP)] appear similar between CR and TRF protocols, as do the dopaminergic responses in the mesocorticolimbic circuit. However, ghrelin and leptin signaling via the melanocortin system appears to improve energy balance signals and reduce hyperphagia following TRF, which has not been reported in CR. In addition to satiety systems, CR and TRF also influence circadian rhythms. CR influences the suprachiasmatic nucleus (SCN) or the primary circadian clock as seen by increased clock gene expression. In contrast, TRF appears to affect both the SCN and the peripheral clocks, as seen by phasic changes in the non-SCN (potentially the elusive food entrainable oscillator) and metabolic clocks. The peripheral clocks are influenced by the primary circadian clock but are also entrained by food timing, sleep timing, and other lifestyle parameters, which can supersede the metabolic processes that are regulated by the primary circadian clock. Taken together, TRF influences hunger/satiety, energy balance systems, and circadian rhythms, suggesting a role for adherence to CR in the long run if implemented using the TRF approach. However, these suggestions are based on only a few studies, and future investigations that use standardized protocols for the evaluation of the effect of these diet patterns (time, duration, meal composition, sufficiently powered) are necessary to verify these preliminary observations.