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Biomedical subjects

Leonie K Heilbronn

Publications and source records attributed to Leonie K Heilbronn.

14 recordsLinked to original sources
PubMed2007

Effect of calorie restriction with or without exercise on body composition and fat distribution.

CONTEXT: There is debate over the independent and combined effects of dieting and increased physical activity on improving metabolic risk factors (body composition and fat distribution). OBJECTIVE: The objective of the study was to conduct a randomized, controlled trial (CALERIE) to test the effect of a 25% energy deficit by diet alone or diet plus exercise for 6 months on body composition and fat distribution. DESIGN: This was a randomized, controlled trial. SETTING: The study was conducted at an institutional research center. PARTICIPANTS: Thirty-five of 36 overweight but otherwise healthy participants (16 males, 19 females) completed the study. INTERVENTION: Participants were randomized to either control (healthy weight maintenance diet, n = 11), caloric restriction (CR; 25% reduction in energy intake, n = 12), or caloric restriction plus exercise (CR+EX; 12.5% reduction in energy intake + 12.5% increase in exercise energy expenditure, n = 12) for 6 months. MAIN OUTCOME MEASURES: Changes in body composition by dual-energy x-ray absorptiometry and changes in abdominal fat distribution by multislice computed tomography were measured. RESULTS: The calculated energy deficit across the intervention was not different between CR and CR+EX. Participants lost approximately 10% of body weight (CR: - 8.3 +/- 0.8, CR+EX: - 8.1 +/- 0.8 kg, P = 1.00), approximately 24% of fat mass (CR: - 5.8 +/- 0.6, CR+EX: - 6.4 +/- 0.6 kg, P = 0.99), and 27% of abdominal visceral fat (CR: 0.9 +/- 0.2, CR+EX: 0.8 +/- 0.2 kg, P = 1.00). Both whole-body and abdominal fat distribution were not altered by the intervention. CONCLUSION: Exercise plays an equivalent role to CR in terms of energy balance; however, it can also improve aerobic fitness, which has other important cardiovascular and metabolic implications.

Abdominal Fat↗
PubMed2006

Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial.

CONTEXT: Prolonged calorie restriction increases life span in rodents. Whether prolonged calorie restriction affects biomarkers of longevity or markers of oxidative stress, or reduces metabolic rate beyond that expected from reduced metabolic mass, has not been investigated in humans. OBJECTIVE: To examine the effects of 6 months of calorie restriction, with or without exercise, in overweight, nonobese (body mass index, 25 to <30) men and women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of healthy, sedentary men and women (N = 48) conducted between March 2002 and August 2004 at a research center in Baton Rouge, La. INTERVENTION: Participants were randomized to 1 of 4 groups for 6 months: control (weight maintenance diet); calorie restriction (25% calorie restriction of baseline energy requirements); calorie restriction with exercise (12.5% calorie restriction plus 12.5% increase in energy expenditure by structured exercise); very low-calorie diet (890 kcal/d until 15% weight reduction, followed by a weight maintenance diet). MAIN OUTCOME MEASURES: Body composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels; protein carbonyls; DNA damage; 24-hour energy expenditure; and core body temperature. RESULTS: Mean (SEM) weight change at 6 months in the 4 groups was as follows: controls, -1.0% (1.1%); calorie restriction, -10.4% (0.9%); calorie restriction with exercise, -10.0% (0.8%); and very low-calorie diet, -13.9% (0.7%). At 6 months, fasting insulin levels were significantly reduced from baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels were unchanged. Core body temperature was reduced in the calorie restriction and calorie restriction with exercise groups (both P<.05). After adjustment for changes in body composition, sedentary 24-hour energy expenditure was unchanged in controls, but decreased in the calorie restriction (-135 kcal/d [42 kcal/d]), calorie restriction with exercise (-117 kcal/d [52 kcal/d]), and very low-calorie diet (-125 kcal/d [35 kcal/d]) groups (all P<.008). These "metabolic adaptations" (~ 6% more than expected based on loss of metabolic mass) were statistically different from controls (P<.05). Protein carbonyl concentrations were not changed from baseline to month 6 in any group, whereas DNA damage was also reduced from baseline in all intervention groups (P <.005). CONCLUSIONS: Our findings suggest that 2 biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that metabolic rate is reduced beyond the level expected from reduced metabolic body mass. Studies of longer duration are required to determine if calorie restriction attenuates the aging process in humans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00099151.

Adult↗
PubMed2006

Muscle-associated triglyceride measured by computed tomography and magnetic resonance spectroscopy.

OBJECTIVE: Muscle triglyceride can be assessed in vivo using computed tomography (CT) and 1H magnetic resonance spectroscopy (MRS), two techniques that are based on entirely different biophysical principles. Little is known, however, about the cross-correlation between these techniques and their test-retest reliability. RESEARCH METHODS AND PROCEDURES: We compared mean muscle attenuation (MA) in soleus and tibialis anterior (TA) muscles measured by CT with intra- and extramyocellular lipids (IMCL and EMCL, respectively) measured by MRS in 51 volunteers (26 to 72 years of age, BMI = 25.5 to 39.3 kg/m2). MA of midthighs was also measured in a subset (n = 19). Test-retest measurements were performed by CT (n = 6) and MRS (n = 10) in separate sets of volunteers. RESULTS: MA of soleus was significantly associated with IMCL (r = -0.64) and EMCL, which by multiple regression analysis was explained mostly by IMCL (p < 0.001) rather than EMCL (beta = -0.010, p = 0.94). Muscle triglyceride was lower in TA than in soleus, and MA of TA was significantly correlated with EMCL (r = -0.40) but not IMCL (r = -0.16). By CT, MA of midthighs was correlated with MA in soleus (r = 0.40, p = 0.07) and whole calf (r = 0.62, p < 0.05). Finally, both MA and IMCL were highly reliable in soleus (coefficient of variation = < 2% and 6.7%, respectively) and less reliable in TA (4% and 10%, respectively). DISCUSSION: These results support the use of both CT and MRS as reliable methods for assessing skeletal muscle lipid.

Adipose Tissue↗
PubMed2006

Decreased expression of adipogenic genes in obese subjects with type 2 diabetes.

OBJECTIVE: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance. RESEARCH METHODS AND PROCEDURES: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARgamma coactivator 1alpha, PPARgamma coactivator 1beta, and PPARdelta] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity. RESULTS: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 +/- 1.9 vs. 7.5 +/- 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 +/- 0.26 vs. 0.78 +/- 0.17 microm; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARgamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07). DISCUSSION: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.

Adipose Tissue↗
PubMed2006

Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects.

OBJECTIVE: The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (S(i)) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables. RESEARCH DESIGN AND METHODS: Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction +12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and S(i) were assessed at baseline and month 6. RESULTS: At baseline, FCS was related to VAT and IHL (P < 0.05) but not to IMCL. FCS was also the strongest determinant of S(i) (P < 0.01). Weight loss at month 6 was 1 +/- 1% (control, mean +/- SE), 10 +/- 1% (CR), 10 +/- 1% (CREX), and 14 +/- 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P < 0.01), but IMCL was unchanged. S(i) was increased at month 6 (P = 0.05) in the CREX (37 +/- 18%) and LCD (70 +/- 34%) groups (P < 0.05) and tended to increase in the CR group (40 +/- 20%, P = 0.08). Together the improvements in S(i) were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS. CONCLUSIONS: Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

Adipose Tissue↗
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↗
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↗
PubMed2003

-308 Nco I polymorphism of tumour necrosis factor alpha in overweight Caucasians.

We investigated whether a polymorphism in the promoter region of the TNFalpha gene (-308 A/G) is associated with reduced weight loss in obese Australian subjects on an energy restricted diet. 189 healthy subjects and 91 subjects with type II diabetes were genotyped for the -308 Nco I polymorphism using PCR-RFLP techniques. A subset of these subjects (211 females and 45 males), were placed on a 30% energy restricted diet (6200 kJ) for 12 weeks. Subjects were assessed every 2 weeks and changes in body weight, waist circumference and BMI were used as determinants of weight loss. Fasting plasma was analysed for glucose, insulin, lipids and free fatty acids. 64% of subjects were GG homozygotes, 31% were AG heterozygotes and 5% were AA homozygotes. There was no significant difference between the allele frequency in healthy subjects (0.21) and type 2 diabetic patients (0.24). The presence of the -308 A/G polymorphism did not significantly influence initial BMI, the amount of weight lost (GG, 8.1+/-0.65 kg, AG, 6.9+/-0.77 kg, AA, 7.6+/-0.12 kg), waist circumference or any metabolic variable. The AA variant at position -308 in the promoter region of the TNFalpha gene does not influence the amount of weight lost in overweight and obese men and women on a 30% energy restricted diet.

Australia↗
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↗
PubMed2002

Association between HDL-cholesterol and the Taq1B polymorphism in the cholesterol ester transfer protein gene in obese women.

Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol transport via HDL-C and this activity may be increased in obese subjects. In normal weight subjects the Taq1B variant of the CETP gene is associated with lower CETP activity and higher HDL-C. The aim of this study was to examine the relationship between the Taq1B polymorphism and HDL-C in obese women before and after weight loss. A total of 245 women (41 with type 2 diabetes) were genotyped for the Taq1B variant. Plasma lipids, insulin, glucose and oral glucose tolerance were also measured before and after weight loss. When all subjects were examined together the Taq1B genotype was not associated with HDL-C. However, when non-diabetic subjects were divided by median fasting insulin, a strong linear association was observed between Taq1B genotype and HDL-C in subjects below median for fasting insulin (B1B1 1.19+/-0.07 mmol/l, B1B2 1.35+/-0.06, B2B2 1.71+/-0.09, P<0.000). This association was not observed in subjects with fasting insulin above median or subjects with type 2 diabetes, either before or after weight loss. Therefore, the B2B2 genotype is associated with elevated HDL-C in obese women with low fasting insulin only. Improved insulin sensitivity during weight loss did not change this relationship in women with high fasting insulin or type 2 diabetes.

Carrier Proteins↗
PubMed2002

The effect of high- and low-glycemic index energy restricted diets on plasma lipid and glucose profiles in type 2 diabetic subjects with varying glycemic control.

OBJECTIVE: To determine whether glycemic index (GI) differentially affects improved glucose and lipid profiles observed during weight loss in overweight subjects previously diagnosed with type 2 diabetes with variable glucose tolerance. METHODS: Twenty-three female and twenty-two male overweight subjects participated in 12 weeks of energy restriction (average BMI 33.2 kg/m2, age 56.7 years, glycated hemoglobin (GHb) 6.7%). After a four-week run-in on a high saturated fat (SFA) diet (1540 kcal/day, 17% SFA), the free-living subjects were randomly assigned to either a high- (75 GI units) or low- (43 GI units) GI diet (1440 kcal/day, 60% carbohydrate, 5% SFA) for eight weeks. Weight, serum lipids, plasma glucose and glycated hemoglobin were measured every four weeks. An oral glucose tolerance test (OGTT) was also performed at baseline, weeks 4 and 12. From the baseline OGTT results subjects were divided into three groups of low, median and high glucose tolerance. RESULTS: At baseline, BMI, age and glycated hemoglobin concentrations were not different between subjects allocated to the high- or low-GI diets. After four weeks, weight loss was 3.6+/-0.3 kg. Fasting glucose (-5.6%), glycated hemoglobin (-2.8%), area under the glucose curve (-13.0%) and triglyceride (-13.8%) concentrations were reduced (p < 0.02). Between weeks 4 and 12 reductions were observed in weight (-4.9%), fasting glucose (-4.6%), area under glucose curve (-10.1%), glycated hemoglobin (-7.2%), triglyceride (-7.5%) and LDL-C (-13.2%) concentrations. Weight loss was not different between low and high-GI diets. However, glycated hemoglobin was reduced twofold more in subjects consuming a low-GI diet as compared to subjects consuming a high-GI diet, but this was not statistically significant. LDL concentrations were also reduced more in subjects with low glucose tolerance on the low-GI diet (p = 0.02). CONCLUSION: Weight loss produces substantial improvements in glycemic control and lipoprotein metabolism. Lowering the glycemic index of high carbohydrate, low fat diets increases the fall in LDL cholesterol in subjects with type 2 diabetes with low glucose tolerance, but has little effect on glycemic control.

Blood Glucose↗