Julia Volaufova

Effect of calorie restriction on resting metabolic rate and spontaneous physical activity.

Objective: It is unclear if resting metabolic rate (RMR) and spontaneous physical activity (SPA) decrease in weight‐reduced non‐obese participants. Additionally, it is unknown if changes in SPA, measured in a respiratory chamber, reflect changes in free‐living physical activity level (PAL).

Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

Objective: Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures.

Effects of Tyrosine, Phentermine, Caffeine D-amphetamine, and Placebo on Cognitive and Motor Performance Deficits During Sleep Deprivation

Abstract Cognitive and motor performance are critical in many circumstances and are impaired by sleep deprivation. We administered placebo, tyrosine 150 mg/kg, caffeine 300 mg/70 kg, phentermine 37.5 mg and d-amphetamine 20 mg at 15.30 h following overnight sleep deprivation and compare their effects on cognitive and motor performance in healthy young men. Tests of visual scanning, running memory, logical reasoning, mathematical processing, the Stroop task, four-choice serial reaction time, time wall take, pursuit tracking, visual vigilance, Trails (B) task and long-term memory were evaluated at standardized intervals before, during and after sleep deprivation and drugs. Performance decrements with sleep deprivation occurred in visual scanning, running memory, logical reasoning, mathematical processing, the Stroop test, the time wall test, tracking and visual vigilance. Interestingly, with sleep deprivation some tests improved and others did not deteriorate. Improvements with medication following sleep deprivation were seen in running memory, logical reasoning, mathematical processing, tracking and visual vigilance. Although less effective than d-amphetamine, tyrosine improved performance on several tests. We conclude that all drugs tested improved at least some aspects of cognitive and motor performance after sleep deprivation. As a naturally occurring amino acid, and thus amenable to nutritional strategies, tyrosine may deserve further testing.

Energy Intake and Energy Expenditure: A Controlled Study Comparing Dietitians and Non-dietitians

BACKGROUND Underreporting of food intake has been commonly observed. We hypothesized that experience with recording dietary information might increase the accuracy of the records. To test this hypothesis, we compared energy intake and energy expenditure in dietitians-who are experienced in recording food intake-with those of non-dietitians, whose only exposure to training to record food was in the context of this trial. SUBJECTS/SETTING Subjects for this study were 10 female registered dietitians and 10 women of comparable age and weight who were not dietitians. DESIGN This study compared the energy intake obtained from 7-day food records with energy expenditure measured over the corresponding 7-day period using doubly labeled water. STATISTICAL ANALYSIS Data were compared by an analysis of variance METHODS All subjects were trained to provide a 7-day weighed food intake record. Energy expenditure was measured with doubly labeled water over the 7 days when the weighed food intake record was obtained. A total of 10 dietitians and a control of group of 10 women of similar age and weight were recruited for this study. Participants were told that the goal was to record food intake as accurately as possible, because it would be compared with the simultaneous measurement of energy expenditure determined by doubly labeled water. RESULTS The energy expenditure of the dietitians and controls were not different (2,154+/-105 [mean+/- standard error of the mean] kcal/day for dietitians and 2,315 +/- 90 kcal/ day for controls). The dietitians underreported their energy intake obtained from the food records by an average of 223 +/- 116 kcal/day, which was not different from their energy expenditure. Participants in the control group, as hypothesized, significantly underreported their energy intake (429 +/- 142 kcal/day, P < .05). CONCLUSION Dietitians estimated their energy intake more accurately than non-dietitians, suggesting that familiarity with and interest in keeping food records may lead to more reliable estimates of energy intake.

Permanent Cardiac Pacing in Children: Choosing the Optimal Pacing Site A Multicenter Study

Background— We evaluated the effects of the site of ventricular pacing on left ventricular (LV) synchrony and function in children requiring permanent pacing. Methods and Results— One hundred seventy-eight children (aged <18 years) from 21 centers with atrioventricular block and a structurally normal heart undergoing permanent pacing were studied cross-sectionally. Median age at evaluation was 11.2 (interquartile range, 6.3–15.0) years. Median pacing duration was 5.4 (interquartile range, 3.1–8.8) years. Pacing sites were the free wall of the right ventricular (RV) outflow tract (n=8), lateral RV (n=44), RV apex (n=61), RV septum (n=29), LV apex (n=12), LV midlateral wall (n=17), and LV base (n=7). LV synchrony, pump function, and contraction efficiency were significantly affected by pacing site and were superior in children paced at the LV apex/LV midlateral wall. LV dyssynchrony correlated inversely with LV ejection fraction (R=0.80, P=0.031). Pacing from the RV outflow tract/lateral RV predicted significantly decreased LV function (LV ejection fraction <45%; odds ratio, 10.72; confidence interval, 2.07–55.60; P=0.005), whereas LV apex/LV midlateral wall pacing was associated with preserved LV function (LV ejection fraction ≥55%; odds ratio, 8.26; confidence interval, 1.46–47.62; P=0.018). Presence of maternal autoantibodies, gender, age at implantation, duration of pacing, DDD mode, and QRS duration had no significant impact on LV ejection fraction. Conclusions— The site of ventricular pacing has a major impact on LV mechanical synchrony, efficiency, and pump function in children who require lifelong pacing. Of the sites studied, LV apex/LV midlateral wall pacing has the greatest potential to prevent pacing-induced reduction of cardiac pump function.

HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.

The search for longevity‐determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

Impaired Insulin Sensitivity and Elevated Ectopic fat in Healthy Obese vs. Nonobese Prepubertal Children

Insulin sensitivity is impaired and ectopic fat (accretion of lipids outside of typical adipose tissue depots) increased in obese adults and adolescents. It is unknown how early in life this occurs; thus, it is important to evaluate young children to identify potential factors leading to the development of metabolic syndrome. We examined an ethnically diverse cohort of healthy, exclusively prepubertal children (N = 123; F = 57, M = 66; age 8.04 ± 0.77 years) to examine differences in insulin sensitivity and ectopic and visceral fat deposition between obese and nonobese youth. Obesity was categorized by age‐ and sex‐adjusted BMI z‐scores (nonobese = z‐score <2 (N = 94) and obese = z‐score ≥2 (N = 29)). Insulin sensitivity was assessed by both a frequently sampled intravenous glucose tolerance test (Si) and the homeostatic model assessment of insulin resistance (HOMAIR). Intramyocellular lipids (IMCLs) from soleus and intrahepatic lipids (IHLs) were assessed by magnetic resonance spectroscopy, visceral adipose tissue (VAT) by magnetic resonance imaging, and total body fat by dual‐energy X‐ray absorptiometry. We also examined serum lipids (total cholesterol, triglycerides, high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol) and blood pressure (diastolic and systolic). Obese children exhibited significantly lower Si (5.9 ± 5.98 vs. 13.43 ± 8.18 (mµ/l)−1·min−1, P = 0.01) and HDL‐C and higher HOMAIR (1.68 ± 1.49 vs. 0.63 ± 0.47, P < 0.0001), IMCL (0.74 ± 0.39 vs. 0.44 ± 0.21% water peak, P < 0.0001), IHL (1.49 ± 1.13 vs. 0.54 ± 0.42% water peak, P < 0.0001), VAT (20.16 ± 8.01 vs. 10.62 ± 5.44 cm2, P < 0.0001), total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and systolic blood pressure relative to nonobese children. These results confirm significantly increased ectopic fat and insulin resistance in healthy obese vs. nonobese children prior to puberty. Excessive adiposity during early development appears concomitant with precursors of type 2 diabetes and the metabolic syndrome.

Social Engagement and Health in Younger, Older, and Oldest-Old Adults in the Louisiana Healthy Aging Study

Social support has been shown to influence health outcomes in later life. In this study, we focus on social engagement as an umbrella construct that covers select social behaviors in a life span sample that included oldest-old adults, a segment of the adult population for whom very little data currently exist. We examined relationships among social engagement, positive health behaviors, and physical health to provide new evidence that addresses gaps in the extant literature concerning social engagement and healthy aging in very old adults. Participants were younger (21-59 years), older (60-89 years), and oldest-old (90-97 years) adults (N = 364) in the Louisiana Healthy Aging Study (LHAS). Linear regression analyses indicated that age, gender, and hours spent outside of the house were significantly associated with self-reported health. The number of clubs and hours outside of home were more important factors in the analyses of objective health status than positive health behaviors, after considering age group and education level. These data strongly suggest that social engagement remains an important determinant of physical health into very late adulthood. The discussion focuses on practical applications of these results including social support interventions to maintain or improve late-life health.

The gene structure and minimal promoter of the human agouti related protein.

The murine agouti related protein (mAGRP) is upregulated in obese and diabetic mice and stimulates hyperphagia when administered intracerebroventricularly (i.c.v.) or when overexpressed in transgenic mice. The human ortholog, hAGRP, has been isolated and has similar molecular and physiological properties. Here, we report the complete gene structure of the human AGRP gene and upstream regions with differential promoter activity. A polymorphism, A67T, in the third exon was identified but was not associated with obesity- or type 2 diabetes-related phenotypes. Putative binding sites for transcription factors were identified in the promoter of the gene including recognition sites for the signal transducers and activators of transcription (STATs) that may potentially mediate leptins action in the hypothalamus. The upstream non-coding exon had significant promoter activity in a periphery- but not so in a hypothalamus-derived cell line, suggesting that it might contain the minimal promoter required for expression of the short transcript of hAGRP in the periphery.

Corrective responses in human food intake identified from an analysis of 7-d food-intake records

BACKGROUND We tested the hypothesis that ad libitum food intake shows corrective responses over periods of 1-5 d. DESIGN This was a prospective study of food intake in women. METHODS Two methods, a weighed food intake and a measured food intake, were used to determine daily nutrient intake during 2 wk in 20 women. Energy expenditure with the use of doubly labeled water was done contemporaneously with the weighed food-intake record. The daily deviations in macronutrient and energy intake from the average 7-d values were compared with the deviations observed 1, 2, 3, 4, and 5 d later to estimate the corrective responses. RESULTS Both methods of recording food intake gave similar patterns of macronutrient and total energy intakes and for deviations from average intakes. The intraindividual CVs for energy intake ranged from +/-12% to +/-47% with an average of +/-25%. Reported energy intake was 85.5-95.0% of total energy expenditure determined by doubly labeled water. Significant corrective responses were observed in food intakes with a 3- to 4-d lag that disappeared when data were randomized within each subject. CONCLUSIONS Human beings show corrective responses to deviations from average energy and macronutrient intakes with a lag time of 3-4 d, but not 1-2 d. This suggests that short-term studies may fail to recognize important signals of food-intake regulation that operate over several days. These corrective responses probably play a crucial role in bringing about weight stability.