Susan B. Racette

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

Background—Obesity is a risk factor for impaired cardiac performance, particularly in women. Animal studies suggest that alterations in myocardial fatty acid metabolism and efficiency in obesity can cause decreased cardiac performance. In the present study, we tested the hypothesis that myocardial fatty acid metabolism and efficiency are abnormal in obese women. Methods and Results—We studied 31 young women (body mass index [BMI] 19 to 52 kg/m2); 19 were obese (BMI >30 kg/m2). Myocardial oxygen consumption (M&OV0312;o2) and fatty acid uptake (MFAUp), utilization (MFAU), and oxidation (MFAO) were quantified by positron emission tomography. Cardiac work was measured by echocardiography, and efficiency was calculated as work/M &OV0312;o2. BMI correlated with M &OV0312;o2 (r =0.58, P =0.0006), MFAUp (r =0.42, P <0.05), and efficiency (r = −0.40, P <0.05). Insulin resistance, quantified by the glucose area under the curve (AUC) during an oral glucose tolerance test, correlated with MFAUp (r =0.55, P <0.005), MFAU (r =0.62, P <0.001), and MFAO (r =0.58, P <0.005). A multivariate, stepwise regression analysis showed that BMI was the only independent predictor of M&OV0312;o2 and efficiency (P =0.0005 and P <0.05, respectively). Glucose AUC was the only independent predictor of MFAUp, MFAU, and MFAO (P <0.05, <0.005, and <0.005, respectively). Conclusions—In young women, obesity is a significant predictor of increased M&OV0312;o2 and decreased efficiency, and insulin resistance is a robust predictor of MFAUp, MFAU, and MFAO. This increase in fatty acid metabolism and decrease in efficiency is concordant with observations made in experimental models of obesity. These metabolic changes may play a role in the pathogenesis of decreased cardiac performance in obese women.

Weight Changes, Exercise, and Dietary Patterns During Freshman and Sophomore Years of College

Weight gain and behavioral patterns during college may contribute to overweight and obesity in adulthood. The aims of this study were to assess weight, exercise, and dietary patterns of 764 college students (53% women, 47% men) during freshman and sophomore years. Students had their weight and height measured and completed questionnaires about their recent exercise and dietary patterns. At the beginning of freshman year, 29% of students reported not exercising, 70% ate fewer than 5 fruits and vegetables daily, and more than 50% ate fried or high-fat fast foods at least 3 times during the previous week. By the end of their sophomore year, 70% of the 290 students who were reassessed had gained weight (4.1 ± 3.6 kg, p> .001), but there was no apparent association with exercise or dietary patterns. Future research is needed to assess the contributions of fat, muscle, and bone mass to observed weight gain and to determine the health implications of these findings.

Changes in Weight and Health Behaviors from Freshman through Senior Year of College.

OBJECTIVE To assess weight changes, exercise and diet behaviors among college students from the beginning of freshman year until the end of senior year. DESIGN Longitudinal observational study. SETTING Private university in St. Louis, Missouri. PARTICIPANTS College students (138 females, 66 males). MAIN OUTCOME MEASURES Weight and height were measured, body mass index (BMI) was calculated, and exercise and dietary behaviors were assessed by questionnaire. ANALYSIS Changes in weight, BMI, exercise, and dietary patterns from the beginning of freshman year to the end of senior year. RESULTS Females gained 1.7 +/- 4.5 kg (3.75 +/- 9.92 lb) [mean +/- SD] from freshman to senior year, and males gained 4.2 +/- 6.4 kg (9.26 +/- 14.11 lb) (both P < .001). Weight changes were highly variable between students, however, ranging from -13.2 kg to +20.9 kg (-29.10 to +46.08 lb). CONCLUSIONS AND IMPLICATIONS Weight gain was common but variable among college students. Importantly, exercise and dietary patterns did not meet the recommended guidelines for many college students, which may have long-term health implications.

Hunter-gatherer energetics and human obesity

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than that of Westerners after controlling for body size. The metabolic cost of walking (kcal kg−1 m−1) and resting (kcal kg−1 s−1) were also similar among Hadza and Western groups. The similarity in metabolic rates across a broad range of cultures challenges current models of obesity suggesting that Western lifestyles lead to decreased energy expenditure. We hypothesize that human daily energy expenditure may be an evolved physiological trait largely independent of cultural differences.

Comparison of heart rate and physical activity recall with doubly labeled water in obese women

Comparison of heart rate and physical activity recall with doubly labeled water in obese women. Med. Sci. Sports Exerc., Vol. 27, No. 1, pp. 126-133, 1995. Accurate methods of estimating total daily energy expenditure (TDEE) that are inexpensive and differentiate activities of varying intensities are needed in obesity research. We compared minute-by-minute heart rate (HR) monitoring and the 7-d physical activity recall (PAR) questionnaire with doubly labeled water (DLW) for the measurement of TDEE and physical activity in 14 obese women (45% +/- 4% fat, mean +/- SD) before and during 12 wk of weight reduction. TDEE was measured over 2 wk by DLW. HR monitoring was conducted for 3 d, with individual VO2/HR calibrations applied to HR data above 3 METs. PAR revealed the amount of time spent in sleep, moderate, hard, and very hard activities during 1 wk, with time spent in light activities determined by difference. Mean TDEE values, expressed as the % difference from DLW, prior to weight loss were -5.2 +/- 10.8% by HR and 3.4 +/- 14.4 by PAR, and during the diet were + 0.9 +/- 14.1% by HR and + 0.9 +/- 14.7% by PAR. Individual variability was high for both HR (-24.0 to + 25.6%) and PAR (-27.4 to + 36.2%). Energy expended in physical activity prior to weight loss were 3.97 +/- 1.23 MJ.d-1 by DLW, 3.91 +/- 0.90 by HR, and 4.79 +/- 0.95 by PAR. During weight loss, physical activity values by DLW, HR, and PAR were 4.31 +/- 1.18, 4.84 +/- 2.22, and 4.64 +/- 1.06 MJ.d-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Design and Conduct of the CALERIE Study: Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy

BACKGROUND In a robust and consistent manner, sustained caloric restriction (CR) has been shown to retard the aging process in a variety of animal species. Nonhuman primate studies suggest that CR may have similar effects in longer-lived species. The CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy) research program is the first systematic investigation of CR in nonobese human beings. In the phase 2 study, it is hypothesized that 2 years of sustained CR, involving a 25% reduction of ad libitum energy intake, results in beneficial effects similar to those observed in animal studies. This article presents the design and implementation of this study. METHODS The study is a multicenter, parallel-group, randomized controlled trial. A sample of 225 participants (22.0 ≤ body mass index [BMI] < 28.0 kg/m(2)) is being enrolled with 2:1 allocation to CR. RESULTS An intensive dietary and behavioral intervention was developed to achieve 25% CR and sustain it over the 2 years. Adherence is monitored using a doubly labeled water technique. Primary outcomes are resting metabolic rate and core temperature, and are assessed at baseline and at 6-month intervals. Secondary outcomes address oxyradical formation, cardiovascular risk markers, insulin sensitivity and secretion, immune function, neuroendocrine function, quality of life and cognitive function. Biologic materials are stored in a central repository. CONCLUSIONS An intricate protocol has been developed to conduct this study. Procedures have been implemented to safeguard the integrity of the data and the conclusions drawn. The results will provide insight into the detrimental changes associated with the human aging process and how CR mitigates these effects.

Dose effects of dietary phytosterols on cholesterol metabolism: a controlled feeding study

BACKGROUND Phytosterol supplementation of 2 g/d is recommended by the National Cholesterol Education Program to reduce LDL cholesterol. However, the effects of different intakes of phytosterol on cholesterol metabolism are uncertain. OBJECTIVE We evaluated the effects of 3 phytosterol intakes on whole-body cholesterol metabolism. DESIGN In this placebo-controlled, crossover feeding trial, 18 adults received a phytosterol-deficient diet (50 mg phytosterols/2000 kcal) plus beverages supplemented with 0, 400, or 2000 mg phytosterols/d for 4 wk each, in random order. All meals were prepared in a metabolic kitchen; breakfast and dinner on weekdays were eaten on site. Primary outcomes were fecal cholesterol excretion and intestinal cholesterol absorption measured with stable-isotope tracers and serum lipoprotein concentrations. RESULTS Phytosterol intakes (diet plus supplements) averaged 59, 459, and 2059 mg/d during the 3 diet periods. Relative to the 59-mg diet, the 459- and 2059-mg phytosterol intakes significantly (P < 0.01) increased total fecal cholesterol excretion (36 +/- 6% and 74 +/- 10%, respectively) and biliary cholesterol excretion (38 +/- 7% and 77 +/- 12%, respectively) and reduced percentage intestinal cholesterol absorption (-10 +/- 1% and -25 +/- 3%, respectively). Serum LDL cholesterol declined significantly only with the highest phytosterol dose (-8.9 +/- 2.3%); a trend was observed with the 459-mg/d dose (-5.0 +/- 2.1%; P = 0.077). CONCLUSIONS Dietary phytosterols in moderate and high doses favorably alter whole-body cholesterol metabolism in a dose-dependent manner. A moderate phytosterol intake (459 mg/d) can be obtained in a healthy diet without supplementation. This trial was registered at clinicaltrials.gov as NCT00860054.

Worksite Opportunities for Wellness (WOW): Effects on cardiovascular disease risk factors after 1 year

OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors. METHODS In St Louis, Missouri from 2005 to 2006, 151 employees (134 F, 17 M, 81% overweight/obese) participated in a cohort-randomized trial comparing assessments + intervention (worksite A) with assessments only (worksite B) for 1 year. All participants received personal health reports containing their assessment results. The intervention was designed to promote physical activity and favorable dietary patterns using pedometers, healthy snack cart, WeightWatchers(R) meetings, group exercise classes, seminars, team competitions, and participation rewards. Outcomes included BMI, body composition, blood pressure, fitness, lipids, and Framingham 10-year coronary heart disease risk. RESULTS 123 participants, aged 45+/-9 yr, with BMI 32.9+/-8.8 kg/m(2) completed 1 year. Improvements (P< or =0.05) were observed at both worksites for fitness, blood pressure, and total-, HDL-, and LDL-cholesterol. Additional improvements occurred at worksite A in BMI, fat mass, Framingham risk score, and prevalence of the metabolic syndrome; only the changes in BMI and fat mass were different between worksites. CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors, but many of the improvements were achieved with worksite health assessments and personalized health reports in the absence of an intervention.

Effects of Trace Components of Dietary Fat on Cholesterol Metabolism: Phytosterols, Oxysterols, and Squalene

The effect of dietary fats on serum cholesterol is widely assumed to be due solely to the fatty acids and cholesterol they contain. Phytosterols, sterol oxidation products, and sterol precursors such as squalene, however, are often present in dietary fats. Little is known of the physiology of these substances in natural foods and most published diet studies do not consider them at all. Supplementation of the diet with high-dose phytosterols is now recommended for prevention of heart disease, but both recent and old data strongly suggest that the lower levels of phytosterols naturally present in vegetable fats may also reduce cholesterol absorption and serum cholesterol substantially. Moreover, unmeasured phytosterols may confound otherwise well-controlled diet studies because there is an inverse correlation between phytosterol and saturated fatty acid content of vegetable fats. Sterol oxidation products, many of which are found in foods, are potent regulators of lipoprotein and cholesterol transport pathways in vitro. Squalene is a phytosterol precursor abundant in olive oil that is at least partly absorbed and then quantitatively converted to cholesterol. The effects of dietary triglyceride-derived fatty acids have not been experimentally separated from the effects of trace fat components in most clinical studies. A better understanding of the activity of sterol-related dietary components is needed to reduce variability in diet studies, accurately assess the effects of dietary fatty acids and to maximize the effectiveness of dietary treatment for hypercholesterolemia.

Phytosterol glycosides reduce cholesterol absorption in humans.

Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (P<0.0001) and phytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.