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2.
Nat Aging ; 3(3): 248-257, 2023 03.
Article in English | MEDLINE | ID: mdl-37118425

ABSTRACT

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1-3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5-7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11-13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14-16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18-20.


Subject(s)
Caloric Restriction , DNA Methylation , Humans , Adult , Caloric Restriction/methods , Energy Intake , Aging/genetics , Longevity
4.
Eur J Clin Nutr ; 64(12): 1481-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20808333

ABSTRACT

BACKGROUND/OBJECTIVES: Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. SUBJECTS/METHODS: In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers. RESULTS: The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), P<0.0001) and 79% higher fecal cholesterol excretion (1322±112 (1083.2, 1483.3) vs 739±97 mg/day (530.1, 930.2), P<0.0001) relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 µg/mg (0.98, 1.53), P<0.0001). LDL-cholesterol was similar between diets. CONCLUSIONS: Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.


Subject(s)
Anticholesteremic Agents/pharmacology , Cholesterol, LDL/metabolism , Cholesterol/metabolism , Diet , Phytosterols/pharmacology , Anticholesteremic Agents/metabolism , Cholesterol/blood , Cholesterol, LDL/blood , Cross-Over Studies , Female , Food , Humans , Male , Middle Aged , Phytosterols/metabolism
5.
Int J Obes (Lond) ; 30(5): 837-43, 2006 May.
Article in English | MEDLINE | ID: mdl-16418761

ABSTRACT

OBJECTIVE: To evaluate the relation between body fatness (%Fat) and body mass index (BMI) and to evaluate the validity of the BMI standards for obesity established by the NIH in older black and white postmenopausal women. RESEARCH METHODS: Height, weight, BMI, and %Fat, assessed by DXA, were determined for 296 healthy, independently living women ranging in age from 50 to 80 years (M+/-s.d.; 64.4+/-7.8 years). RESULTS: Per NIH guidelines, 32% were classified as obese (> or = 30 kg/m2, mean BMI = 28.1+/-5.5 kg/m2). In contrast, using the %Fat criterion of 38% advocated by Lohman to define obesity, 47% of our sample was obese (mean %Fat=37.3+/-6.2%). A moderately high curvilinear relation existed between BMI and %Fat (R = 0.82, SEE = 3.57 %Fat, P<0.05). Race added meaningfully to the prediction of %Fat (P<0.05) such that for the same BMI, black women will have 1% lower body fatness than white women. Based on a %Fat > or = 38 as the criterion for obesity, receiver operating characteristic (ROC) analysis, performed separately by race, indicated that the currently accepted BMI cutpoint for obesity produced low sensitivity (69% and 61% for black and white women, respectively). Alternatively, BMI values > or = 28.4 kg/m2 for black women and > or = 26.9 kg/m2 for white women to define obesity maximized classification accuracy. CONCLUSION: We conclude that current BMI categories may not be appropriate for identifying obesity among postmenopausal women. Furthermore, the relation between BMI and %Fat is different in black compared to white women but remains constant from the sixth through the eighth decade of life.


Subject(s)
Black People , Body Mass Index , Obesity/classification , Obesity/ethnology , White People , Absorptiometry, Photon , Aged , Aged, 80 and over , Body Composition , Female , Humans , Middle Aged , Obesity/physiopathology , Postmenopause/metabolism , ROC Curve , Sensitivity and Specificity
6.
Obes Res ; 9(6): 348-55, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11399781

ABSTRACT

OBJECTIVE: Previous studies have demonstrated the benefit of short-term diets on glucose tolerance in obese individuals. The purpose of this study was to evaluate the effectiveness of modest lifestyle changes in maintaining improvements in glucose tolerance induced by short-term energy restriction in obese African Americans with impaired glucose tolerance or type 2 diabetes mellitus. RESEARCH METHODS AND PROCEDURES: An intervention group (n = 45; 47 +/- 1 year [mean +/- SE]), 105 +/- 4 kg; body mass index: 39 +/- 1 kg/m(2)) received an energy-restricted diet (943 +/- 26 kcal/d) for 1 week, followed by a lifestyle program of reduced dietary fat (-125 kcal/d) and increased physical activity (+125 kcal/d) for 1 year. Body weight and plasma concentrations of glucose, insulin, and C-peptide during an oral glucose tolerance test were measured at baseline, 1-week, and 4-month intervals. A control group (n = 24; 48 +/- 1 year; 110 +/- 5 kg; body mass index: 41 +/- 2 kg/m(2)) underwent these measurements at 4-month intervals. RESULTS: No changes in weight or glucose tolerance were observed in the control group. The intervention group had significant (p < 0.05) improvements in body weight and glucose tolerance in response to the 1-week diet, which persisted for 4 months (p < 0.001 vs. control for change in weight). A total of 19 subjects (42%) continued the intervention program for 1 year, with sustained improvements (weight: -4.6 +/- 1.0 kg; p < 0.001 vs. control; oral glucose tolerance test glucose area: -103 +/- 44 mM. min; p < 0.05 vs. control). DISCUSSION: A modest lifestyle program facilitates weight loss and enables improvements in glucose tolerance to be maintained in obese individuals with abnormal glucose tolerance. However, attrition was high, despite the mild nature of the program.


Subject(s)
Black or African American , Diabetes Mellitus, Type 2/diet therapy , Diet, Reducing , Glucose Intolerance/diet therapy , Life Style , Obesity/complications , Adult , Aged , Area Under Curve , Blood Glucose/analysis , Case-Control Studies , Diabetes Mellitus, Type 2/ethnology , Dietary Fats/administration & dosage , Exercise , Female , Glucose Intolerance/ethnology , Glucose Tolerance Test , Humans , Lipids/blood , Male , Middle Aged , Obesity/diet therapy , Obesity/ethnology , Weight Loss
7.
Am J Physiol Regul Integr Comp Physiol ; 279(3): R944-50, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10956252

ABSTRACT

We evaluated palmitate rate of appearance (R(a)) in plasma during basal conditions and during a four-stage epinephrine infusion plus pancreatic hormonal clamp in nine white and nine black women with abdominal obesity, who were matched on fat-free mass, total and percent body fat, and waist-to-hip circumference ratio. On the basis of single-slice magnetic resonance imaging analysis, black women had the same amount of subcutaneous abdominal fat but less intra-abdominal fat than white women (68 +/- 9 vs. 170 +/- 14 cm(2), P < 0.05). Basal palmitate R(a) was lower in black than in white women (1.95 +/- 0.26 vs. 2.88 +/- 0.23 micromol. kg fat-free mass(-1). min(-1), P < 0.005), even though plasma insulin and catecholamine concentrations were the same in both groups. Palmitate R(a) across a physiological range of plasma epinephrine concentrations remained lower in black women, because the increase in palmitate R(a) during epinephrine infusion was the same in both groups. We conclude that basal and epinephrine-stimulated palmitate R(a) is lower in black than in white women with abdominal obesity. The differences in basal palmitate kinetics are not caused by alterations in plasma insulin or catecholamine concentrations or lipolytic sensitivity to epinephrine. The lower rate of whole body fatty acid flux and smaller intra-abdominal fat mass may have clinical benefits because of the relationship between excessive fatty acid availability and metabolic diseases.


Subject(s)
Energy Metabolism/physiology , Obesity/ethnology , Obesity/metabolism , Palmitic Acid/pharmacokinetics , Abdomen , Adipose Tissue/metabolism , Adult , Black People , Body Composition , Carbon Radioisotopes , Energy Metabolism/drug effects , Epinephrine/blood , Epinephrine/pharmacology , Female , Humans , Insulin/blood , Kinetics , Lipolysis/physiology , Pancreas/metabolism , Sympathomimetics/blood , Sympathomimetics/pharmacology , White People
8.
J Clin Endocrinol Metab ; 85(4): 1498-504, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10770188

ABSTRACT

The aim of this study was to evaluate in premenopausal women (10 sedentary obese women) the effects of 10 days of exercise on the suppression of whole body and regional lipolysis by insulin. Lipolysis was determined using 2H5-glycerol infusion and microdialysis of sc adipose tissue during a two-stage hyperinsulinemic-euglycemic clamp [10 (LO) and 20 (MO) mU/m x min]. Microdialysis probes were positioned in abdominal and femoral sc adipose tissue to monitor interstitial glycerol and blood flow. Basal plasma glycerol was 86.7 +/-17.0 and 100.3 +/- 19.8 micromol/L before and after training, respectively (P < 0.05). Plasma glycerol was suppressed to a greater extent after [to 47 +/- 5% (LO) and 42 +/- 5% (MO) of basal] than before [to 62 +/- 8% (LO) and 55 +/- 8% (MO) of basal] training. The rate of appearance of glycerol was suppressed to 49 +/- 7% and 40 +/- 5% of basal during LO and to 38 +/- 5% and 30 +/- 4% of basal during MO (P < 0.05) before and after training, respectively. There were no differences in the suppression of lipolysis in abdominal as well as femoral sc adipose tissue as evidenced by similar reductions in dialysate glycerol levels before and after training in each of these tissues. The results indicate that the antilipolytic response to insulin can be improved through endurance exercise training. Intraabdominal adipose tissue or skeletal muscle may be the site of improved antilipolytic response to insulin after training, as improvement was not evident in abdominal or femoral sc adipose tissue.


Subject(s)
Exercise , Insulin/pharmacology , Lipolysis/drug effects , Physical Endurance , Adipose Tissue/blood supply , Adipose Tissue/metabolism , Blood Glucose/metabolism , Body Composition , Deuterium , Female , Glucose Clamp Technique , Glycerol/blood , Humans , Microdialysis , Obesity/metabolism , Oxygen Consumption , Premenopause
9.
J Clin Endocrinol Metab ; 84(11): 3886-95, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10566624

ABSTRACT

The aim of this study was to evaluate in premenopausal women (six endurance-trained nonobese, six sedentary nonobese, and five sedentary obese) the suppression of whole body and regional lipolysis by insulin. Lipolysis was determined using 2H5-glycerol infusion and microdialysis of sc adipose tissue (AT) during a two-stage [6-10 (low; LO) and 12-20 (moderate; MOD) mU/m x min] hyperinsulinemic-euglycemic clamp. Microdialysis probes were positioned in abdominal and femoral sc AT to monitor interstitial glycerol and nutritive blood flow. Basal plasma glycerol was 102 +/- 9, 52 +/- 6, and 143 +/- 30 micromol/L in endurance-trained nonobese, sedentary nonobese, and sedentary obese, respectively (P < 0.05, sedentary nonobese < endurance-trained nonobese, sedentary obese). The plasma glycerol concentration was decreased (P < 0.05) to a greater extent in endurance-trained nonobese and sedentary nonobese [both to approximately 50% (LO) and approximately 45% (MOD) of basal] than in sedentary obese [to 72% (LO) and 63% (MOD) of basal]. The rate of appearance of glycerol was suppressed to 36 +/- 7%, 44 +/- 10%, and 62 +/- 7% of basal during LO in endurance-trained nonobese, sedentary nonobese, and sedentary obese, respectively (P < 0.05, endurance-trained nonobese < sedentary obese), and to 34 +/- 3%, 36 +/- 5%, and 53 +/- 8% of basal during MOD, respectively (P < 0.05, endurance-trained nonobese < sedentary obese). There were no between-group differences in the suppression of lipolysis in abdominal sc AT, as evidenced by similar reductions in dialysate glycerol levels [all to approximately 65% (LO) and approximately 55% (MOD) of basal]. Femoral dialysate glycerol was reduced (P < 0.05) more in sedentary nonobese and endurance-trained nonobese (to approximately 75% of basal) than in sedentary obese (to 90% of basal) during LO, but to a similar extent (to approximately 60% of basal) in all groups during MOD. The results indicate that the sedentary obese women had whole body resistance to the suppression of lipolysis by insulin. Intraabdominal AT may be the site of resistance, as resistance was not evident in abdominal or femoral sc AT.


Subject(s)
Exercise/physiology , Insulin/pharmacology , Lipolysis/drug effects , Obesity/metabolism , Abdomen , Adipose Tissue/blood supply , Adult , Blood Glucose/metabolism , Body Composition , Body Constitution , Deuterium , Female , Femur , Glucose Clamp Technique , Glycerol/blood , Humans , Insulin/administration & dosage , Insulin/blood , Kinetics , Microdialysis , Oxygen Consumption , Physical Endurance
10.
J Clin Endocrinol Metab ; 84(10): 3726-31, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10523021

ABSTRACT

Insulin-induced leptinemia in humans appears to be blunted by insulin resistance. We therefore examined the relationship between insulin action and plasma leptin by monitoring regional and whole body lipolysis and plasma leptin levels in 15 premenopausal women (body fat range, 14-59%) during a two-stage euglycemic clamp (insulin was infused 90 min each at 6-10 and 12-20 mU/m2 x min). Microdialysis probes were placed in abdominal and femoral sc adipose tissue. Subjects were given a primed, constant infusion of a stable isotope tracer (2H5-glycerol), and plasma glycerol isotope enrichments were analyzed by mass spectrometry to determine glycerol kinetics. Although there was no mean change in plasma leptin during the clamp (baseline, 16.6 +/- 4.5 ng/mL; final, 16.3 +/- 4.3 ng/mL), there was large interindividual variability in the changes in plasma leptin (range, -18% to +19%). Changes in plasma leptin during the clamp stages were correlated with abdominal dialysate glycerol concentrations (r = -0.44; P < 0.05), but not femoral dialysate glycerol concentrations (r = -0.15), the rate of appearance of glycerol in plasma (r = 0.005), or plasma insulin levels (r = 0.16). The results suggest that insulin-induced changes in plasma leptin are more related to the lipolytic state (i.e. low leptin response when lipolysis is high) of abdominal sc adipose tissue than that of other fat depots.


Subject(s)
Abdomen , Adipose Tissue/metabolism , Insulin/pharmacology , Leptin/blood , Lipolysis , Adult , Blood Circulation/physiology , Female , Glycerol/blood , Humans , Hyperinsulinism/blood , Hyperinsulinism/chemically induced , Hyperinsulinism/metabolism , Hyperinsulinism/physiopathology , Insulin/blood , Time Factors
11.
J Appl Physiol (1985) ; 87(1): 222-6, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10409578

ABSTRACT

The purpose of this investigation was to determine whether endurance exercise training increases the ability of human skeletal muscle to accumulate glycogen after exercise. Subjects (4 women and 2 men, 31 +/- 8 yr old) performed high-intensity stationary cycling 3 days/wk and continuous running 3 days/wk for 10 wk. Muscle glycogen concentration was measured after a glycogen-depleting exercise bout before and after endurance training. Muscle glycogen accumulation rate from 15 min to 6 h after exercise was twofold higher (P < 0.05) in the trained than in the untrained state: 10.5 +/- 0.2 and 4.5 +/- 1.3 mmol. kg wet wt(-1). h(-1), respectively. Muscle glycogen concentration was higher (P < 0.05) in the trained than in the untrained state at 15 min, 6 h, and 48 h after exercise. Muscle GLUT-4 content after exercise was twofold higher (P < 0.05) in the trained than in the untrained state (10.7 +/- 1.2 and 4.7 +/- 0.7 optical density units, respectively) and was correlated with muscle glycogen concentration 6 h after exercise (r = 0.64, P < 0.05). Total glycogen synthase activity and the percentage of glycogen synthase I were not significantly different before and after training at 15 min, 6 h, and 48 h after exercise. We conclude that endurance exercise training enhances the capacity of human skeletal muscle to accumulate glycogen after glycogen-depleting exercise.


Subject(s)
Exercise/physiology , Glycogen/metabolism , Muscle Proteins , Muscle, Skeletal/metabolism , Physical Endurance/physiology , Adult , Citrate (si)-Synthase/metabolism , Dietary Carbohydrates/administration & dosage , Exercise Test , Female , Glucose Transporter Type 4 , Glycogen Synthase/metabolism , Hexokinase/metabolism , Humans , Male , Monosaccharide Transport Proteins/metabolism
12.
J Appl Physiol (1985) ; 86(6): 1930-5, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10368358

ABSTRACT

The effects of a 10-day low-calorie diet (LCD; n = 8) or exercise training (ET; n = 8) on insulin secretion and action were compared in obese men (n = 9) and women (n = 7), aged 53 +/- 1 yr, with abnormal glucose tolerance by using a hyperglycemic clamp with superimposed arginine infusion and a high-fat drink. Body mass (LCD, 115 +/- 5 vs. 110 +/- 5 kg; ET, 111 +/- 7 vs. 109 +/- 7 kg; P < 0. 01) and fasting plasma glucose (LCD, 115 +/- 10 vs. 99 +/- 4 mg/dl; ET, 112 +/- 4 vs. 101 +/- 5 mg/dl, P < 0.01) and insulin (LCD, 23.9 +/- 5.6 vs. 15.2 +/- 3.9 microU/ml; ET, 17.6 +/- 1.9 vs. 13.9 +/- 2. 4 microU/ml; P < 0.05) decreased in both groups. There was a 40% reduction in plasma insulin during hyperglycemia (0-45 min) after LCD (peak: 118 +/- 18 vs. 71 +/- 14 microU/ml; P < 0.05) and ET (69 +/- 14 vs. 41 +/- 7 microU/ml; P < 0.05) and trends for reductions during arginine infusion and a high-fat drink. The 56% increase in glucose uptake after ET (4.95 +/- 0.90 vs. 7.74 +/- 0.82 mg. min-1. kg fat-free mass-1; P < 0.01) was significantly (P < 0.01) greater than the 19% increase (5.72 +/- 1.12 vs. 6.80 +/- 0.94 mg. min-1. kg fat-free mass-1; P = not significant) that occurred after LCD. The marked increase in glucose disposal after ET, despite lower insulin levels, suggests that short-term exercise is more effective than diet in enhancing insulin action in individuals with abnormal glucose tolerance.


Subject(s)
Diet, Reducing , Exercise/physiology , Glucose Intolerance/therapy , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Arginine , Blood Glucose/metabolism , Body Composition/physiology , Body Weight/physiology , Dietary Fats , Female , Glucose Clamp Technique , Glucose Intolerance/diet therapy , Glucose Tolerance Test , Humans , Hypoglycemic Agents/blood , Insulin/blood , Male , Middle Aged , Obesity/blood , Oxygen Consumption/physiology
13.
J Appl Physiol (1985) ; 83(3): 897-903, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9292478

ABSTRACT

Muscle glycogen accumulation was determined in six trained cyclists (Trn) and six untrained subjects (UT) at 6 and either 48 or 72 h after 2 h of cycling exercise at approximately 75% peak O2 uptake (VO2 peak), which terminated with five 1-min sprints. Subjects ate 10 g carbohydrate . kg-1 . day-1 for 48-72 h postexercise. Muscle glycogen accumulation averaged 71 +/- 9 (SE) mmol/kg (Trn) and 31 +/- 9 mmol/kg (UT) during the first 6 h postexercise (P < 0.01) and 79 +/- 22 mmol/kg (Trn) and 60 +/- 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogen concentration was 164 +/- 21 mmol/kg (Trn) and 99 +/- 16 mmol/kg (UT) 48-72 h postexercise (P < 0.05). Muscle GLUT-4 content immediately postexercise was threefold higher in Trn than in UT (P < 0.05) and correlated with glycogen accumulation rates (r = 0.66, P < 0.05). Glycogen synthase in the active I form was 2.5 +/- 0.5, 3.3 +/- 0.5, and 1.0 +/- 0.3 micromol . g-1 . min-1 in Trn at 0, 6, and 48 or 72 h postexercise, respectively; corresponding values were 1.2 +/- 0.3, 2.7 +/- 0.5, and 1.6 +/- 0.3 micromol . g-1 . min-1 in UT (P < 0.05 at 0 h). Plasma insulin and plasma C-peptide area under the curve were lower in Trn than in UT over the first 6 h postexercise (P < 0.05). Plasma creatine kinase concentrations were 125 +/- 25 IU/l (Trn) and 91 +/- 9 IU/l (UT) preexercise and 112 +/- 14 IU/l (Trn) and 144 +/- 22 IU/l (UT; P < 0.05 vs. preexercise) at 48-72 h postexercise (normal: 30-200 IU/l). We conclude that endurance exercise training results in an increased ability to accumulate muscle glycogen after exercise.


Subject(s)
Glycogen/metabolism , Muscle Proteins , Muscle, Skeletal/metabolism , Physical Endurance/physiology , Physical Fitness , Adult , Bicycling , Blood Glucose/metabolism , Body Composition/physiology , Creatine Kinase/metabolism , Diet , Glucose Transporter Type 4 , Glycogen Synthase/metabolism , Hormones/blood , Humans , Male , Monosaccharide Transport Proteins/metabolism , Muscle, Skeletal/enzymology
14.
Am J Clin Nutr ; 66(1): 33-7, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9209166

ABSTRACT

The aim of this study was to determine whether serum leptin concentrations are reduced in response to short-term energy restriction in centrally obese individuals with impaired glucose tolerance or non-insulin-dependent diabetes mellitus. Twenty African Americans [16 females and 4 males, 44 +/- 7 y (x +/- SD), 107.2 +/- 23.8 kg, 39 +/- 7% body fat] consumed a 7-d energy-restricted diet (4.03 +/- 0.72 MJ/d) of whole foods. Oral-glucose-tolerance tests (OGTTs) were performed before and immediately after the diet to assess changes in serum leptin, glucose, and insulin concentrations. Baseline leptin concentration correlated significantly with percentage body fat (r = 0.80), body mass index (r = 0.72), fat mass (4 = 0.64), waist-height ratio (r = 0.6), body weight (r = 0.59, all P < 0.01), waist circumference (r = 0.49), and basal insulin concentration (r = 0.48, both P < 0.05). Seven days of energy restriction resulted in significant reductions (P < 0.005) in leptin (-6.1 +/- 8.4 micrograms/L), basal glucose (-0.9 +/- 0.8 mmol/L), OGTT glucose area under the curve (-158 +/- 164 mmol/L), and basal insulin concentration (-34 +/- 69 pmol/L, P < 0.05). In addition, there was a trend for a reduction in OGTT insulin area under the curve (-15,567 +/- 3,658 pmol/L, P = 0.05), and a tendency for basal insulin and leptin to change together (r = 0.41, P = 0.07). Despite the weight loss of 3.1 +/- 1.3 kg (P < 0.0001), the loss of fat mass was calculated to be only -1.0 +/- 0.1 kg. These results suggest that negative energy balance or improved insulin action was responsible for the changes in leptin, glucose, and insulin concentrations. In summary, short-term energy restriction effectively reduced serum leptin concentrations and improved glucose tolerance and insulin action in obese individuals with impaired or diabetic glucose tolerance.


Subject(s)
Black People , Diabetes Mellitus, Type 2/metabolism , Obesity/metabolism , Proteins/metabolism , Adult , Area Under Curve , Blood Glucose/metabolism , Energy Intake , Female , Glucose Intolerance/metabolism , Humans , Insulin/blood , Leptin , Male , Middle Aged , Weight Loss
15.
J Clin Endocrinol Metab ; 82(7): 2275-7, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9215306

ABSTRACT

Leptin, the protein product of the ob gene, may be involved in the regulation of energy balance. Although a clear relationship between energy intake and plasma leptin concentrations has been demonstrated in humans, little is known about the effect of exercise on leptin metabolism. In the present study, we evaluated abdominal adipose tissue leptin production in vivo by arteriovenous balance at rest and during 60 min of moderate-intensity cycle ergometer exercise (50% of maximal heart rate) in five sedentary male subjects (mean age 38.4 +/- 1.7 yr, body mass index (28.4 +/- 4.2 kg/m2). Blood samples were taken simultaneously from an abdominal vein, draining sc adipose tissue, and a radial artery, at rest and every 10 min during exercise. Adipose tissue blood flow was determined by the xenon washout technique. Plasma leptin concentrations did not change throughout exercise and were the same as the values obtained during resting conditions. Average net adipose tissue leptin production rates during exercise (3.07 +/- 0.89 ng/100 g-1.min-1) also were similar to resting values (3.86 +/- 0.95 ng/100 g-1.min-1). These results demonstrate that plasma leptin concentrations and leptin production do not change during an acute bout of moderate-intensity aerobic exercise.


Subject(s)
Adipose Tissue/metabolism , Exercise , Proteins/metabolism , Adult , Exercise/physiology , Humans , Leptin , Male , Time Factors
16.
J Appl Physiol (1985) ; 80(1): 240-4, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8847309

ABSTRACT

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.


Subject(s)
Exercise Therapy , Insulin/metabolism , Monosaccharide Transport Proteins/metabolism , Muscle Proteins , Physical Endurance/physiology , Running , Adult , Blood Glucose/metabolism , Body Composition/physiology , Female , Glucose Clamp Technique , Glucose Transporter Type 4 , Humans , Insulin/blood , Male , Muscle, Skeletal/metabolism
17.
Obes Res ; 3 Suppl 2: 261s-265s, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8581785

ABSTRACT

Several recent self-reported surveys have suggested that African-American women may engage in less leisure-time physical activity (PA) than whites. Objective measurements of PA have not been performed, however. Therefore, the purpose of this study was to compare the components of energy expenditure, including PA, between black and white obese women. Using the doubly labeled water method, total daily energy expenditure (TDEE), basal metabolic rate (BMR), thermic effect of a meal (TEM), and PA were measured in 14 black and 15 white moderately obese women over 2 weeks. No statistically significant differences were seen between the 2 groups in BMR, TEM or TDEE. Mean PA was significantly (p = 0.05) lower among black women compared to whites when expressed as MJ. d-1 (3.49 vs. 4.30) or kJ.kg-1.d-1 (37.6 vs. 47.7). Our study supports the survey differences seen in PA among black and white women.


Subject(s)
Black or African American , Exercise/physiology , Obesity/physiopathology , White People , Adult , Body Composition/physiology , Body Weight/physiology , Eating/physiology , Energy Metabolism/physiology , Female , Humans , Middle Aged , Obesity/metabolism , Surveys and Questionnaires
18.
Am J Clin Nutr ; 62(2): 345-9, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7625341

ABSTRACT

The effect of aerobic exercise on dietary compliance was assessed in 13 obese women (44 +/- 3% fat) during a 12-wk weight-reduction program (EX group). Seventeen obese women (45 +/- 5% fat) not engaged in aerobic exercise (NX group) served as control subjects. The reducing diets were designed to promote a weight loss of 1 kg/wk, with energy intakes individually prescribed (mean +/- SD: 4.9 +/- 0.6 MJ/d) to approximate 75% of each subject's measured basal metabolic rate. The EX group completed of three 45-min sessions/wk of supervised aerobic exercise at 65% of maximal oxygen consumption (VO2max). Daily energy intakes were calculated by summing changes in body stores, measured by total body water isotope dilution, and total daily energy expenditure, measured by doubly labeled water (DLW). Dietary compliance was assessed by comparing calculated intakes with prescribed intakes. Both the EX and NX groups reported consuming close to their prescribed daily intakes, with differences of -0.08 +/- 0.28 (EX group) and +0.03 +/- 0.57 (NX group) MJ/d, respectively. However, expenditure/balance data determined by the DLW method indicated that the EX subjects exhibited better dietary compliance than the NX subjects, with intakes exceeding those prescribed by only 0.7 +/- 1.5 compared with 2.3 +/- 1.6 MJ/d for the NX subjects (P = 0.01). Therefore, an additional benefit of aerobic exercise during energy restriction is enhanced dietary compliance, which has important implications for the treatment of moderate obesity.


Subject(s)
Diet, Reducing/standards , Energy Metabolism/physiology , Exercise/physiology , Obesity/diet therapy , Patient Compliance , Adult , Affect , Carbon Dioxide/metabolism , Combined Modality Therapy , Deuterium , Eating/physiology , Female , Humans , Methods , Middle Aged , Obesity/physiopathology , Obesity/therapy , Oxygen Consumption/physiology , Oxygen Isotopes , Surveys and Questionnaires
19.
Am J Clin Nutr ; 61(3): 486-94, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7872211

ABSTRACT

To test the benefits of aerobic exercise and dietary carbohydrate during reduced-energy feeding, 23 obese women (44 +/- 4% fat) were randomly assigned to either aerobic exercise (Ex) or no exercise (Nx), and to a low-fat (LF) or low-carbohydrate (LC) reducing diet (5.00 +/- 0.56 MJ/d) for 12 wk. Changes in body composition, postabsorptive resting metabolic rate (RMR), thermic effect of a meal (TEM), and total daily energy expenditure (TDEE) were measured by respiratory gas exchange and doubly labeled water. Significant effects of Ex included a greater loss of fat mass (Ex: -8.8 +/- 2.1 vs Nx: -6.1 +/- 2.3 kg, P = 0.008) and maintenance of TDEE (Ex: +0.07 +/- 1.23 vs Nx: -1.46 +/- 1.04 MJ/d, P = 0.004), due to a difference in physical activity (Ex: +0.75 +/- 1.06 vs Nx: -0.61 +/- 1.03 MJ/d, P = 0.006), which was not attributable solely to the Ex sessions. RMR in both groups decreased comparably (-0.54 MJ/d), and TEM (% of meal) did not change. Diet composition did not significantly influence body composition or energy expenditure changes, but a greater weight loss was observed after the LC than after the LF (-10.6 +/- 2.0 vs -8.1 +/- 3.0 kg, P = 0.037) diet. The addition of aerobic exercise to a low-energy diet was beneficial in the treatment of moderate obesity because of its favorable effects on body composition, physical activity, and TDEE.


Subject(s)
Dietary Carbohydrates/pharmacology , Exercise , Obesity/therapy , Weight Loss , Adult , Body Composition , Energy Intake , Energy Metabolism , Female , Humans , Middle Aged , Obesity/metabolism
20.
Med Sci Sports Exerc ; 27(1): 126-33, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7898328

ABSTRACT

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)


Subject(s)
Energy Metabolism/physiology , Heart Rate/physiology , Obesity/physiopathology , Physical Exertion/physiology , Activities of Daily Living , Adult , Basal Metabolism/physiology , Body Water/metabolism , Deuterium , Female , Humans , Mental Recall , Middle Aged , Obesity/diet therapy , Obesity/metabolism , Oxygen Consumption/physiology , Oxygen Isotopes , Reproducibility of Results , Sleep/physiology , Weight Loss
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