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Biomedical subjects

Eric Ravussin

Publications and source records attributed to Eric Ravussin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Microanalysis of eating behavior of three leptin deficient adults treated with leptin therapy.

Leptin deficiency has been associated with extreme obesity and hyperphagia in rodents and humans. A rare genetic disorder in humans yields the absence of the hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare cases have indicated that therapy using leptin injections can yield significant weight loss and changes in appetite. The aim of this report on acute leptin therapy in three leptin deficient adults was to provide a microanalysis of changes in eating behavior and ratings of hunger and satiety. In addition to substantial weight loss, 15 weeks of leptin therapy was associated with approximately 50% reduction in food intake and substantial changes in ratings of hunger and satiety before most meals. After short-term leptin therapy, the three participants ate until ratings indicated they were satiated, which was comparable to the ratings before leptin therapy. These findings suggest that one of the primary effects of acute leptin therapy may be to reduce the ravenous hunger associated with leptin deficiency, resulting in reduced food intake and significant weight loss. These results are discussed in the context of the scientific literature pertaining to leptin and its effects on appetite and obesity.

Adult↗
PubMed2005

Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting.

OBJECTIVE: Alternate day fasting may extend lifespan in rodents and is feasible for short periods in nonobese humans. The aim of this study was to examine the effects of 3 weeks of alternate day fasting on glucose tolerance and skeletal muscle expression of genes involved in fatty acid transport/oxidation, mitochondrial biogenesis, and stress response. RESEARCH METHODS AND PROCEDURES: Glucose and insulin responses to a standard meal were tested in nonobese subjects (eight men and eight women; BMI, 20 to 30 kg/m(2)) at baseline and after 22 days of alternate day fasting (36 hour fast). Muscle biopsies were obtained from a subset of subjects (n = 11) at baseline and on day 21 (12-hour fast). RESULTS: Glucose response to a meal was slightly impaired in women after 3 weeks of treatment (p < 0.01), but insulin response was unchanged. However, men had no change in glucose response and a significant reduction in insulin response (p < 0.03). There were no significant changes in the expression of genes involved in mitochondrial biogenesis or fatty acid transport/oxidation, although a trend toward increased CPT1 expression was observed (p < 0.08). SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). DISCUSSION: Alternate day fasting may adversely affect glucose tolerance in nonobese women but not in nonobese men. The gene expression results indicate that fatty acid oxidation and mitochondrial biogenesis are unaffected by alternate day fasting. However, the increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents.

Adult↗
PubMed2005

Alternate-day fasting in nonobese subjects: effects on body weight, body composition, and energy metabolism.

BACKGROUND: Prolonged dietary restriction increases the life span in rodents. Some evidence suggests that alternate-day fasting may also prolong the life span. OBJECTIVE: Our goal was to determine whether alternate-day fasting is a feasible method of dietary restriction in nonobese humans and whether it improves known biomarkers of longevity. DESIGN: Nonobese subjects (8 men and 8 women) fasted every other day for 22 d. Body weight, body composition, resting metabolic rate (RMR), respiratory quotient (RQ), temperature, fasting serum glucose, insulin, free fatty acids, and ghrelin were assessed at baseline and after 21 d (12-h fast) and 22 d (36-h fast) of alternate-day fasting. Visual analogue scales were used to assess hunger weekly. RESULTS: Subjects lost 2.5 +/- 0.5% of their initial body weight (P < 0.001) and 4 +/- 1% of their initial fat mass (P < 0.001). Hunger increased on the first day of fasting and remained elevated (P < 0.001). RMR and RQ did not change significantly from baseline to day 21, but RQ decreased on day 22 (P < 0.001), which resulted in an average daily increase in fat oxidation of > or =15 g. Glucose and ghrelin did not change significantly from baseline with alternate-day fasting, whereas fasting insulin decreased 57 +/- 4% (P < 0.001). CONCLUSIONS: Alternate-day fasting was feasible in nonobese subjects, and fat oxidation increased. However, hunger on fasting days did not decrease, perhaps indicating the unlikelihood of continuing this diet for extended periods of time. Adding one small meal on a fasting day may make this approach to dietary restriction more acceptable.

Adult↗
PubMed2005

Habitual physical activity in children: the role of genes and the environment.

BACKGROUND: Understanding the factors that contribute to physical inactivity in children is important because sedentary behavior strongly relates to metabolic disorders such as obesity and diabetes. OBJECTIVE: We aimed to quantify the genetic and environmental influences on physical activity energy expenditure (PAEE) in 100 sex-concordant dizygotic (n = 38) and monozygotic (n = 62) twin pairs aged 4-10 y. DESIGN: Resting metabolic rate (RMR) was assessed by using respiratory gas exchange, total energy expenditure (TEE) by using doubly labeled water, and body composition by using dual-energy X-ray absorptiometry. Structural equation modeling was used to partition the phenotypic variance into additive genetic (a2) and common (c2) and unshared (e2) environmental components. RESULTS: Because PAEE [TEE - (RMR + 0.1 x TEE)] depends on body weight, which is highly heritable, we tested several models: 1) after adjustment for age, sex, ethnicity, study date, season, and weight, a2 explained none of the phenotypic variance in PAEE (95% CI: 0%, 38%), whereas c2 and e2 accounted for 69% (33%, 77%; P = 0.001) and 31% (23%, 39%; P < 0.001) of the variance, respectively; 2) after adjustment for the cofactors in model 1, a2 explained 19% of the phenotypic variance in TEE (0%, 60%; P = 0.13), whereas c2 and e2 accounted for 59% (16%, 79%; P = 0.007) and 23% (17%, 31%; P < 0.0001) of the variance, respectively; 3) in models adjusted as above (excluding weight), a2 explained no variance in physical activity level (TEE/RMR) (0%, 32%; P = 0.50), whereas c2 and e2 explained 65% (34%, 60%; P = 0.001) and 35% (28%, 45%; P < 0.0001) of the variance, respectively. CONCLUSIONS: Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability.

Absorptiometry, Photon↗
PubMed2005

Impact of lifestyle on prevalence of kidney disease in Pima Indians in Mexico and the United States.

Pima Indians in the United States and Mexico share a common genetic background but have very different lifestyles. Comparisons were made of the frequency of obesity, diabetes, hypertension, and kidney disease in these geographically separated but susceptible populations. Mexican Pimas had higher levels of physical activity, less obesity, and a lower prevalence of diabetes than their US Pima counterparts. Mean blood pressure rose with worsening glucose tolerance, and the prevalence of elevated urinary albumin excretion was higher in patients with diabetes than in those without, regardless of whether they lived in the United States or Mexico. These findings illustrate the importance of lifestyle in the development of diabetes and in the subsequent occurrence of diabetic kidney disease.

Adult↗
PubMed2005

Genetic and physiological factors in obesity.

Body weight is determined by the interaction of the genetic makeup of an individual and the environment in which that person is living. The control systems that regulate body weight are numerous and include signals from fat that travel to the hypothalamus where cognitive and internal signals are integrated. The integration of these signals involves a complex array of neuropeptides, neurotransmitters and structural circuits. These circuits regulate appetite, intake and energy expenditure. Recent studies demonstrate that the theory of a thrifty genotype is probably correct. Some people are more susceptible to our obesogenic environment than others. Some people are able to overwhelm their genetics by voluntarily increasing energy expenditure and decreasing food intake; a feat that is rarely accomplished and requires a Herculean effort. As we better understand the environmental, genetic, physiological, and behavioral aspects of obesity, we will undoubtedly develop better strategies and therapies for obesity.

Body Mass Index↗
PubMed2004

Energy restriction and aging.

PURPOSE OF REVIEW: The focus of this review is on current research involving long-term calorie restriction and the resulting changes observed in possible biomarkers of aging. Special emphasis will be given to the basic and clinical science studies which are currently investigating the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age and obesity in humans. RECENT FINDINGS: Prolonged calorie restriction has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, worms, fish, rats, and mice. Mechanisms of this lifespan extension via calorie restriction are not fully elucidated, but possibly involve significant alterations in energy metabolism, oxidative damage, insulin sensitivity, and functional changes in both the neuroendocrine and sympathetic nervous systems. Ongoing studies of prolonged energy restriction in humans are now making it possible to analyze changes in these aging biomarkers to unravel some of the mechanisms of its antiaging phenomenon. SUMMARY: With the incremental expansion of research endeavors in the area of energy or calorie restriction, data on the effects of calorie restriction in animal models and humans are becoming more accessible. Detailed analyses from controlled human trials involving long-term calorie restriction will allow investigators to link observed alterations in body composition down to changes in molecular pathways and gene expression, with their possible effects on the biomarkers of aging.

Aging↗
PubMed2004

Reproducibility of endurance performance on a treadmill using a preloaded time trial.

PURPOSE: The purpose of this study was to establish a highly reproducible test to measure endurance performance in runners. METHODS: We evaluated the reproducibility of endurance performance during a 10-km time trial performed on a treadmill after a 90-min preload run at 65% of maximal oxygen uptake VO2max). After screening and a practice test, eight endurance runners (4 men, 4 women, 33.4 +/- 10.1 yr, VO2max = 60.3 +/- 6.3 mL x kg(-1) x min(-1) in men and 51.8 +/- 2.2 mL x kg(-1) x min(-1) in women, mean +/- SD) completed two preloaded time trial tests spaced 3-4 wk apart in men and one menstrual cycle apart in women. A high-carbohydrate diet (15% protein, 10% fat, 75% carbohydrate) was provided the day before both tests. RESULTS: Runners completed time trial 1 and time trial 2 in 45:41 +/- 4:45 and 45:24 +/- 5:03 min:s, respectively (43:29 +/- 5:02 and 43:12 +/- 5:14 min:s for men and 47:53 +/- 3:47 and 47:35 +/- 4:23 min:s for women, trials 1 and 2, respectively). The within-subject coefficient of variation for 10-km time was 1.00% +/- 0.25% (point estimate +/- estimated standard error) (0.54% +/- 0.19% for men and 1.26% +/- 0.45% for women). CONCLUSION: These results suggest that performance measured as time to complete a 10-km time trial on a treadmill after a 90-min preload is extremely reliable and may be useful for future research assessing the effect of diet, ergogenic substances, or training methods on endurance running performance.

Adolescent↗
PubMed2003

Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort.

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P=.023 and.043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N=56; P=.033) and all the diabetics (n=6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P=.014), diastolic blood pressure (P=.009), and sagittal diameter (P=.032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.

Adiponectin↗
PubMed2003

Calorie restriction and aging: review of the literature and implications for studies in humans.

Calorie restriction (CR) extends life span and retards age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. The mechanism or mechanisms through which this occurs are unclear. CR reduces metabolic rate and oxidative stress, improves insulin sensitivity, and alters neuroendocrine and sympathetic nervous system function in animals. Whether prolonged CR increases life span (or improves biomarkers of aging) in humans is unknown. In experiments of nature, humans have been subjected to periods of nonvolitional partial starvation. However, the diets in almost all of these cases have been of poor quality. The absence of adequate information on the effects of good-quality, calorie-restricted diets in nonobese humans reflects the difficulties involved in conducting long-term studies in an environment so conducive to overfeeding. Such studies in free-living persons also raise ethical and methodologic issues. Future studies in nonobese humans should focus on the effects of prolonged CR on metabolic rate, on neuroendocrine adaptations, on diverse biomarkers of aging, and on predictors of chronic age-related diseases.

Aging↗
PubMed2003

Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians.

The hypothalamo-pituitary-adrenal axis and sympathetic nervous system (SNS) interact to maintain cardiovascular and metabolic homeostasis, especially during stress. Pima Indians have a low SNS activity, which may contribute to both their increased risk of obesity and reduced risk of hypertension. Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol and muscle SNS activity [muscle sympathetic nervous system activity (MSNA), microneurography] in 58 males [27 Pimas/31 Caucasians]. Seven Pimas and 12 Caucasians were randomized to a double-blind, placebo-controlled, cross-over study to examine the effect of overnight partial chemical adrenalectomy (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P < 0.006). No correlation was found between fasting cortisol and basal MSNA. Administration of metyrapone did not lead to significant changes in MSNA. In response to a hydrocortisone infusion, MSNA decreased in Pima Indians (P = 0.03) but not in Caucasians (P = 0.7). Our data indicate that the low SNS activity that predisposes Pima Indians to obesity is not due to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population.

Adult↗
PubMed2002

Tasting a liquid meal after a prolonged fast is associated with preferential activation of the left hemisphere.

We used positron emission tomographic scanning of the brain and measures of regional cerebral blood flow to investigate the response of 44 right-handed people to the oral administration of 2 ml of a liquid formula meal after a 36 h fast (and shortly before the administration of a satiating amount of the same meal). Several areas of the left hemisphere were significantly more activated than the contralateral, including the frontal operculum, ventral insula, and piriform cortex. In contrast with reports of right-hemisphere dominance in chemosensory perception in non-hungry individuals, our study reveals a preferential activation of the left hemisphere when people who are very hungry are briefly exposed to the chemical and physical properties of a liquid meal. This raises the possibility that the physiological context in which perception takes place (i.e. extreme vs moderate vs no hunger) may importantly affect the brain representation of chemosensory stimuli.

Adult↗
PubMed2002

Emerging paradigms for understanding fatness and diabetes risk.

It is widely accepted that increasing adiposity is associated with insulin resistance and increased risk of type 2 diabetes. The predominant paradigm used to explain this link is the portal/visceral hypothesis. This hypothesis proposes that increased adiposity, particularly in the visceral depots, leads to increased free fatty acid flux and inhibition of insulin action via Randle's effect in insulin-sensitive tissues. Recent data do not entirely support this hypothesis. As such, two new paradigms have emerged that may explain the established links between adiposity and disease.

Diabetes Mellitus↗
PubMed2002

Role of ghrelin polymorphisms in obesity based on three different studies.

OBJECTIVE: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. RESEARCH METHODS AND PROCEDURES: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. RESULTS: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). DISCUSSION: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

Abdomen↗
PubMed2002

Plasma adiponectin levels are not associated with fat oxidation in humans.

OBJECTIVE: To test the hypothesis that low adiponectin is associated with low fat oxidation in humans. RESEARCH METHODS AND PROCEDURES: We measured plasma adiponectin concentrations in 75 healthy, nondiabetic Pima Indians (age, 28 +/- 7 years; 55 men and 20 women; body fat, 29.7 +/- 7.5%) and 18 whites [(age, 33 +/- 8 years; 14 men and 4 women; body fat, 28.2 +/- 10.8% (means +/- SD)] whose body composition was measured by DXA and 24-hour energy expenditure (24-hour EE) by a respiratory chamber. Respiratory quotient (an estimate of whole-body carbohydrate/lipid oxidation rate) was calculated over 24 hours (24-hour RQ). RESULTS: Before correlational analyses, waist-to-thigh ratio (WTR) and percentage of body fat (PFAT) were adjusted for age, sex, and race; 24-hour EE was adjusted for fat mass and fat-free mass, and 24-hour RQ were adjusted for energy balance. Plasma adiponectin concentrations were negatively correlated with WTR (r = -0.42, p < 0.0001) and PFAT (r = -0.46, p < 0.0001). There was no correlation between plasma adiponectin concentrations and 24-hour RQ, (r = 0.09, p = 0.36) before or after adjustment for PFAT (r = 0.001, p = 0.99, respectively, partial correlation), and no correlation was found between plasma adiponectin concentrations and 24-hour EE (r = -0.12, p = 0.27). DISCUSSION: Our cross-sectional data do not suggest physiological concentrations of fasting plasma adiponectin play a role in the regulation of whole-body fat oxidation or energy expenditure in resting conditions. Whether administration of adiponectin to individuals with low levels of this hormone will increase their fat oxidation rates/energy expenditure remains to be established.

Absorptiometry, Photon↗
PubMed2002

Sex differences in the human brain's response to hunger and satiation.

BACKGROUND: Sex differences in eating behavior are well documented, but it is not known whether these differences have neuroanatomical correlates. Recent neuroimaging studies have provided functional maps of the human cerebral areas activated in response to hunger and satiation. OBJECTIVE: The objective of this study was to assess whether the brain's response to a meal is sex-specific. DESIGN: Using positron emission tomography, we measured regional cerebral blood flow, a marker of neuronal activity, to investigate the functional neuroanatomy of hunger (36-h fast) and satiation (in response to a liquid meal) in 22 women and 22 men. RESULTS: We observed extensive similarities, as well as some differences, between the sexes. In response to hunger, the men tended to have greater activation in the frontotemporal and paralimbic areas than did the women (P < 0.005). In response to satiation, the women tended to have greater activation in the occipital and parietal sensory association areas and in the dorsolateral prefrontal cortex than did the men (P < 0.005); in contrast, the men tended to have greater activation in the ventromedial prefrontal cortex than did the women (P < 0.005). CONCLUSIONS: Despite extensive similarities in the brain responses to hunger and satiation between the men and women, our study showed sex-specific brain responses to a meal that indicate possible differences between men and women in the cognitive and emotional processing of hunger and satiation. This study provides a foundation for investigating the brain regions and cognitive processes that distinguish normal and abnormal eating behavior in men and women.

Adult↗