Influence of BMI and gender on postprandial hormone responses

Objective: Influences of gender and body weight on the hormonal response to eating are not well understood. This study was conducted to determine a convenient time‐point to evaluate peak postprandial hormone responses and to test the hypothesis that gender and BMI interact to produce differences in postprandial secretion of selected humoral markers implicated in hunger and satiety. Research Methods and Procedures: Fasting blood glucose, insulin, leptin, ghrelin, glucagon‐like peptide‐1, and glucagon were measured in normal‐weight (20 ≤ BMI < 25 kg/m²) men (n = 10) and women (n = 9) and obese (BMI ≥ 30 kg/m²) men (n = 9) and women (n = 11). A standard liquid meal was consumed, and humoral measurements were repeated every 10 minutes for 1 hour. Data were analyzed using repeated measures ANOVA with BMI and gender as main effects. Results: Obese subjects had delayed peak insulin responses (p = 0.004), whereas obese men had a delayed nadir ghrelin response (p = 0.05). Obese subjects had higher and more sustained postprandial glucose (p = 0.02), and greater fasting (p = 0.0004) and postprandial insulin (p = 0.0001). Ghrelin decreased after the meal (p = 0.003); the percent change from fasting tended to be reduced in obese subjects (p = 0.07). Men had greater fasting (p = 0.02) and postprandial (p = 0.03) glucagon and a subtle postprandial decline in plasma leptin (p = 0.01). Discussion: Peak hormone responses occurred 20 to 40 minutes after eating. Measurements made during this interval may be useful in evaluating postprandial response magnitude. Peak/nadir responses and time courses of postprandial responses are influenced by gender and BMI. Nutritional studies need to account for variability introduced by these factors.     

Low Resting and Sleeping Energy Expenditure and Fat Use Do Not Contribute to Obesity in Women

Objective: Determine whether sleeping and resting energy expenditure and sleeping, resting, and 24‐hour fuel use distinguish obesity‐prone from obesity‐resistant women and whether these metabolic factors explain long‐term weight gain. Research Methods and Procedures: Forty‐nine previously overweight but currently normal‐weight women were compared with 49 never‐overweight controls. To date, 87% of the 98 women have been re‐evaluated after 1 year of follow‐up, without intervention, and 38% after 2 years. Subjects were studied at a General Clinical Research Center after 4 weeks of tightly controlled conditions of energy balance and macronutrient intake. Forty‐nine obesity‐prone weight‐reduced women were group‐matched with 49 never‐overweight obesity‐resistant controls. All were premenopausal, sedentary, and normoglycemic. Energy expenditure and fuel use were assessed using chamber calorimetry. Body composition was assessed using DXA. Results: At baseline, percent body fat was not different between the obesity‐prone and control women (33 ± 4% vs. 32 ± 5%, respectively; p = 0.22). Analysis of covariance results show that after adjusting for lean and fat mass, sleeping and resting energy expenditure of obesity‐prone women was within 2% of controls. Neither sleeping nor resting energy expenditure nor sleeping, resting, or 24‐hour fuel use was significantly different between the groups (p > 0.25). None of the metabolic variables contributed significantly to patterns of weight gain at 1 or 2 years of follow‐up. Discussion: The results suggest that when resting and sleeping energy expenditure and fuel use are assessed under tightly controlled conditions, these metabolic factors do not distinguish obesity‐prone from obesity‐resistant women or explain long‐term weight changes.     

Association between Serum Leptin Levels and 24‐Hour Blood Pressure in Obese Women

Objective: To assess the relationship between serum leptin and 24‐hour blood pressure (BP) in obese women, according to body fat distribution. Research Methods and Procedures: A cross‐sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24‐hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high‐density lipoprotein cholesterol were also measured. Results: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24‐hour systolic BP (SBP), daytime SBP, nighttime SBP, 24‐hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24‐hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP. Conclusions: Our study shows that serum leptin levels are directly related to 24‐hour BP levels in normotensive women with android fat distribution, independently of BMI.     

Obesity‐related Polymorphisms and Their Associations With the Ability to Regulate Fat Oxidation in Obese Europeans: The NUGENOB Study

Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single‐nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, ?178 A>C CD36 (rs2232169) (P = 0.02), ?22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with ?174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.     

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Objective: To examine the relationship between fasting plasma leptin and 24‐hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. Research Methods and Procedures: Twenty‐one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m²) and 13 lean (body mass index: 20.4 to 24.7 kg/m²) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1–23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty‐four‐hour EE and substrate oxidations were measured by whole‐body indirect calorimetry. SPA was assessed by microwave radar. Results: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24‐hour EE before (r = ?0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24‐hour and resting nonprotein respiratory quotient (r = ?0.47, p < 0.05 and r = ?0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = ?0.41, p = 0.07), 16 weeks (r = ?0.51, p < 0.05), and 24 weeks (r = ?0.50, p < 0.05). Discussion: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.     

Normal Insulin Sensitivity in Lean Offspring of Obese Parents

Objective: Offspring of diabetic or hypertensive patients are insulin resistant at a prediabetic/prehypertensive stage. We tested the hypothesis that insulin action may be impaired in the offspring of obese nondiabetic parents. Research Methods and Procedures: Twenty‐one lean offspring of nonobese subjects [(OL) 22 ± 3 years of age] were matched to 23 lean offspring of obese subjects (OOb) by gender distribution, age, BMI, and waist circumference. Anthropometry, oral glucose tolerance, in vivo insulin sensitivity [by a euglycemic insulin clamp (6 pmol/min per kilogram_FFM; where FFM represents fat‐free mass)], and thermogenesis (by indirect calorimetry) were measured in each subject. The study subjects were from a population of 267 nuclear families (one offspring and both his/her parents) in which there was statistically significant (χ² = 30.2, p = 0.001) concordance of BMI between parents and offspring. Results: In comparing OOb with OL, no statistically significant difference or trend toward a difference was detected in fasting plasma glucose and insulin concentrations, glucose and insulin responses to oral glucose, insulin sensitivity [metabolism value = 45 ± 12 (OOb) vs. 47 ± 17 μmol/min per kilogram_FFM (OL)], insulin‐induced inhibition of protein and lipid oxidation, stimulation of glucose oxidation and nonoxidative glucose disposal, respiratory quotient, resting energy expenditure, and glucose‐induced thermogenesis. Discussion: The metabolic similarity between lean offspring of obese parents and those of nonobese parents suggests that insulin resistance and its correlates are not co‐inherited with the predisposition to develop obesity.     

Postprandial variations of plasma inflammatory markers in abdominally obese men

Objective: Abdominal obesity is associated with a fasting proinflammatory condition. However, not much is known of the potential variations in circulating inflammatory markers after food intake. The purpose of the present study was to examine postprandial changes in plasma tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and C‐reactive protein (CRP) concentrations in men and their potential associations with fat distribution and metabolic profile variables. Research Methods and Procedures: Thirty‐eight men were given a high‐fat meal in the morning after an overnight fast, and TNF‐α, IL‐6, and CRP levels were measured in plasma at 0, 4, and 8 hours after the meal. Physical and metabolic profiles were also assessed for each participant. Results: We observed a substantial increase in circulating IL‐6 levels (p < 0.0001) after the meal. Although postprandial variations in circulating TNF‐α levels across time failed to reach statistical significance (p = 0.02), we noted a significant decrease in plasma TNF‐α concentrations 4 hours (?10%, p < 0.001 vs. 0 hours) after food intake. Plasma CRP levels were not affected by the fat load. We also noted that insulin‐sensitive individuals displayed a less pronounced inflammatory response after food intake than insulin‐resistant subjects. Discussion: Results of the present study show that consumption of a high‐fat meal leads to an increase in plasma IL‐6 concentrations and transient decrease in circulating TNF‐α levels in overweight men. Our results suggest a possible role of insulin resistance in the modulation of the postprandial inflammatory response, which could, in turn, contribute to worsen the state of insulin resistance.     

Effect of Glycemic Load on Peptide‐YY Levels in a Biracial Sample of Obese and Normal Weight Women

Black women suffer a disproportionately higher rate of obesity than their white counterparts. Reasons for this racial disparity may reflect underlying differences in the appetite suppressing peptide‐YY (PYY). The PYY response to food is differentially influenced by macronutrient content but the effect of glycemic load on PYY response is unknown. This study examined whether glycemic load influences fasting and postprandial PYY levels and whether fasting and postprandial PYY levels are lower in obese black women compared to normal weight black women and to white women. Data were collected from 40 women (20 black, 20 white; 10 each normal weight vs. obese) at the University of North Carolina Clinical and Translational Research Center (CTRC). Participants completed in counterbalanced order two 4½‐day weight‐maintenance, mixed macronutrient high vs. low glycemic load diets followed by a test meal of identical composition. Total PYY levels were assessed before and after each test meal. Results show no differences in fasting PYY levels but significantly less postprandial PYY area under the curve (PYY_AUC) in the group of obese black women compared to each other group (race × obesity interaction, P < 0.04). PYY_AUC was positively related to insulin sensitivity (P < 0.004) but was not affected by glycemic load (main and interactive effects, P > 0.27). These findings indicate that postprandial PYY secretion is not affected by glycemic load but is blunted in obese black women compared with normal weight black women and with white women; additionally, they begin to address whether blunted PYY secretion contributes uniquely to the pathogenesis of obesity in black women.     

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats

Objective: The effects of a very low‐carbohydrate (VLC), high‐fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high‐carbohydrate (HC), low‐fat (LF) regimen in dietary obese rats. Research Methods and Procedures: Male Sprague‐Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post‐load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC‐HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one‐half (HC) were pair‐fed an HC‐LF diet (Weeks 9 to 14 at 60% carbohydrate). Results: Energy intakes of pair‐fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. Discussion: When energy intake was matched, the VLC‐HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC‐LF diet.     

Relationship Between Birth Weight and Body Composition,Energy Metabolism,and Sympathetic Nervous System Activity Later in Life

Objective: Epidemiological studies suggest that high birth weight might be associated with an increased risk of obesity later in life. Programming of metabolic, endocrine, and/or autonomic pathways during intrauterine development has been proposed to explain this association. Research Methods and Procedures: To determine the relationship between birth weight and body composition and energy metabolism later in life, we measured fat mass and fat‐free mass (hydrodensitometry or double‐energy X‐ray absorptiometry), 24‐hour energy expenditure, sleeping metabolic rate, and 24‐hour respiratory quotient (respiratory chamber) in 272 adult nondiabetic Pima Indians (161 males/111 females, age 25 ± 5 years, mean ± SD). In these subjects, birth weight varied over a wide range (2000 to 5000 g). Individuals known to be offspring of diabetic pregnancies were excluded. In 44 of the 272 subjects, muscle sympathetic nerve activity was assessed by microneurography. Results: Birth weight was positively correlated with adult height (r = 0.20, p < 0.001) and fat‐free mass (r = 0.21, p < 0.001), but not with fat mass (r = 0.01, not significant). Sleeping metabolic rate, adjusted for age, sex, fat‐free mass, and fat mass, was negatively related to birth weight (r = ?0.13, p < 0.05), whereas adjusted 24‐hour energy expenditure (r = 0.07, not significant) and 24‐hour respiratory quotient (r = ?0.09, not significant) were not. There was no relationship between birth weight and muscle sympathetic nerve activity (r = 0.12, not significant, n = 44). Discussion: In Pima Indians who are not offspring of diabetic pregnancies, high birth weight is associated with increased height and lean body mass, but not with increased adiposity later in life. Although high birth weight may be associated with relatively low resting energy expenditure, it is not associated with major abnormalities in 24‐hour energy metabolism or with low muscle sympathetic nerve activity later in life.     

Racial Differences in Insulin Resistance and Mid‐Thigh Fat Deposition in Postmenopausal Women

Objective: To determine whether racial differences in insulin resistance between African American (AA) and white women exist in postmenopausal women and whether they are related to physical fitness and/or obesity. Research Methods and Procedures: We studied 35 obese AA (n = 9) and white (n = 26) women of comparable maximal oxygen consumption, obesity, and age. Total body fat was measured by DXA. Abdominal and mid‐thigh low‐density lean tissue (a marker of intramuscular fat) were determined with computed tomography. Glucose utilization (M) was measured during the last 30 minutes of a 3‐hour hyperinsulinemic‐euglycemic clamp. Insulin sensitivity was estimated from the relationship of M to the concentration of insulin during the last 30 minutes of the clamp. Results: The percentage of fat and total body fat mass were similar between AA and white women, whereas fat‐free mass was higher in African American women. Visceral adipose tissue was not different between groups, but subcutaneous abdominal fat was 17% higher in the AA than in the white women. AA women had an 18% greater mid‐thigh muscle area (p < 0.01) and a 34% greater mid‐thigh low‐density lean tissue area than the white women. Fasting glucose concentrations were not different, but fasting insulin concentrations were 29% higher in AA women. Glucose utilization was 60% lower in the AA women because of a lower non‐oxidative glucose disposal. Insulin sensitivity was 46% lower in the AA women. Discussion: AA postmenopausal women have more mid‐thigh intramuscular fat, lower glucose utilization, and are less insulin sensitive than white women despite comparable fitness and relative body fat levels.     

Plasma Adiponectin Increases Postprandially in Obese,but not in Lean,Subjects

Objective: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. Research Methods and Procedures: We studied 13 lean and 11 obese subjects after a 10‐hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. Results: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) μg/mL vs. 8.6 (6.5 to 11.3) μg/mL], but rose 4‐fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) μg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) μg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. Discussion: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.     

High‐Fat Diet Feeding Elevates Skeletal Muscle Uncoupling Protein 3 Levels But Not Its Activity in Rats

Objective: The objective of this study is to test the impact of high‐fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole‐body energy homeostasis. Research Methods and Procedures: Sprague–Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low‐fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty‐four‐hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. Results: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2‐fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low‐fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24‐hour energy expenditure. Discussion: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24‐hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3‐mediated uncoupling activity.     

Adipose tissue interleukin-18 mRNA and plasma interleukin-18: effect of obesity and exercise

Objectives: Obesity and a physically inactive lifestyle are associated with increased risk of developing insulin resistance. The hypothesis that obesity is associated with increased adipose tissue (AT) interleukin (IL)‐18 mRNA expression and that AT IL‐18 mRNA expression is related to insulin resistance was tested. Furthermore, we speculated that acute exercise and exercise training would regulate AT IL‐18 mRNA expression. Research Methods and Procedures: Non‐obese subjects with BMI < 30 kg/m² (women: n = 18; men; n = 11) and obese subjects with BMI >30 kg/m² (women: n = 6; men: n = 7) participated in the study. Blood samples and abdominal subcutaneous AT biopsies were obtained at rest, immediately after an acute exercise bout, and at 2 hours or 10 hours of recovery. After 8 weeks of exercise training of the obese group, sampling was repeated 48 hours after the last training session. Results: AT IL‐18 mRNA content and plasma IL‐18 concentration were higher (p < 0.05) in the obese group than in the non‐obese group. AT IL‐18 mRNA content and plasma IL‐18 concentration was positively correlated (p < 0.05) with insulin resistance. While acute exercise did not affect IL‐18 mRNA expression at the studied time‐points, exercise training reduced AT IL‐18 mRNA content by 20% in both sexes. Discussion: Because obesity and insulin resistance were associated with elevated AT IL‐18 mRNA and plasma IL‐18 levels, the training‐induced lowering of AT IL‐18 mRNA content may contribute to the beneficial effects of regular physical activity with improved insulin sensitivity.     

Fasting and Postprandial Plasma Concentrations of Acylation-Stimulation Protein (ASP) in Lean and Obese Pima Indians Compared to Caucasians

WEYER, CHRISTIAN AND RICHARD E. PRATLEY. Fasting and postprandial plasma concentrations of acylation-stimulation protein (ASP) in lean and obese Pima Indians compared to Caucasians. Obes Res. Objective: ASP stimulates the clearance of free fatty acids (FFA) from the circulation and the synthesis of triglycerides (TG) in adipose tissue. We tested whether fasting and post-prandial plasma ASP concentrations are increased in Pima Indians, a population with a very high prevalence of obesity, but a remarkably low prevalence of dyslipidemia. Research Methods and Procedures: Plasma concentrations of ASP, TG, FFA, total cholesterol (CHOL), and insulin (INS) were measured in 15 Pima Indians (P) and 15 Caucasians (C) closely matched for age, sex, and body weight [7 lean and 8 obese subjects, body mass index (BMI) cut-off 30 kg/m²], before and for 4 hours after a standard mixed meal (20% of daily caloric requirements, 41% carbohydrate, 44% fat, 15% protein). Results: Fasting ASP was positively related to percent body fat (dual energy X-ray absorptiometry; r=0. 49, p<0. 01) and to TG and FFA, independently of percent body fat (partial r = 0. 42 and 0. 46, respectively, both p <0. 05). There were no differences in fasting TG, FFA, CHOL, INS, or ASP between lean C and lean P. In contrast, obese P had lower TG, lower CHOL, higher INS and, on average, 27% lower ASP compared to obese C. The ethnic difference in ASP remained after adjustment for TG, FFA, and percent body fat. ASP decreased in response to the meal in all four groups with no differences between groups. There was a significant inverse correlation between preprandial ASP and the change in FFA 60 minutes after the meal (r = ?0. 56, p<0. 001). Discussion: Pima Indians do not have higher plasma ASP concentrations than Caucasians. Whether other alterations in the ASP-pathway, such as increased sensitivity of adipocytes to ASP, contribute to the high prevalence of obesity and low prevalence of dyslipidemia in Pima Indians, remains to be elucidated.     

Glucose response to an oral glucose tolerance test predicts weight change in non-diabetic subjects

Objective: Glucose exerts a dual action in the regulation of energy balance, consisting of inhibition of energy intake and stimulation of energy expenditure. Whether blood glucose affects long‐term regulation of body weight in humans remains to be established. We sought to test the hypothesis that the post‐challenge glucose response is a predictor of weight change. Research Methods and Procedures: We performed a prospective analysis of the impact of glucose response to an oral glucose tolerance test (OGTT) and a mixed‐meal test (MT) on subsequent changes in body weight (BW) on 253 Pima Indians (166 men and 87 women) with normal glucose regulation at baseline and follow‐up (follow‐up: 7 ± 4 years). Main outcome measures included BW change (total, percent, and annual), plasma glucose and insulin concentrations during OGTT and MT [total and incremental areas under the curve (AUCs)], resting metabolic rate (RMR; indirect calorimetry), and insulin action (euglycemic‐hyperinsulinemic clamp). Results: Total and incremental glucose AUCs during the OGTT (but not the MT) were negatively associated with BW change (total, percent, and annual), both before and after adjusting for sex, age, initial BW, follow‐up time, insulin action, RMR, fasting plasma glucose and insulin concentrations, and insulin response. Total and incremental glucose AUCs during the OGTT were independent determinants of final BW with age, initial BW, follow‐up time, fasting plasma insulin concentrations, and RMR. Discussion: Higher post‐challenge glucose response protects against BW gain in subjects with normal glucose regulation. We propose that this action may be because of the effect of glucose on food intake and/or thermogenesis.     

Relationship Between Hunger-Satiety Feelings and Various Metabolic Parameters in Women with Obesity During Controlled Weight Loss

Objective : Satiety plays an important role in weight control. The meaning of fasting hormone levels and satiety feelings, and how post-absorptive changes after meals high in carbohydrate regulate appetite remains to be demonstrated. Research Methods and Procedures : Prospective metabolic study with 25 non-diabetic obese women at the Energy Metabolism Research Unit of the Department of Nutrition Sciences, University of Alabama at Birmingham. We analyzed fasting and postprandial ratings of hunger-satiety and values of various metabolic parameters (serum glucose and insulin, plasma cholecystokinin, respiratory quotient) during controlled weight loss. The postprandial measures were assessed following a test meal providing 320 kcal and yielding a food quotient of 0.89. Results : In the fasting state, there was no correlation between hunger-satiety ratings and any of the measured metabolic parameters. Under postprandial conditions, satiety was positively related to glucose (p = 0.002) and insulin (p = 0.002) responses to the test meal. In multivariate analysis including glucose, insulin, cholecystokinin, hunger-satiety ratings and respiratory quotient, insulin was the only independent predictor of satiety in the postprandial state. Discussion : These data suggest an association between the endogenous insulin response and feelings of postprandial satiety. Insulin's satiation properties, which could well be mediated by other hormones, may represent a primary factor of food intake regulation after meals relatively high in carbohydrate.     

Increased Cortisol Bioavailability,Abdominal Obesity,and the Metabolic Syndrome in Obese Women

Objective: This study was conducted to obtain a detailed profile of hypothalamo‐pituitary‐adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Research Methods and Procedures: Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist‐to hip ratio: women with abdominal body fat distribution (A‐BFD; n = 31) and women with peripheral fat distribution (P‐BFD; n = 22). Results: Comparatively, A‐BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24‐hour urinary free cortisol but increased 24‐hour urinary ratio of cortisone‐to‐cortisol; and 5) no difference in corticosteroid binding protein parameters. Discussion: Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A‐BFD premenopausal obese women.     

Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism

Objective: To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy. Research Methods and Procedures: We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity‐related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study. Results: The strongest results were generation‐specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships. Discussion: These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity‐related phenotypes potentially in an age‐dependent manner.     

Correlation between Serum Resistin Level and Adiposity in Obese Individuals

Objective: Resistin is associated with insulin resistance in mice and may play a similar role in humans. The aim of our study was to examine the relationship of serum resistin level to body composition, insulin resistance, and related obesity phenotypes in humans. Research Methods and Procedures: Sixty‐four young (age 32 ± 10 years), obese (BMI 32.9 ± 5.6), nondiabetic subjects taking no medication, and 15 lean (BMI 21.1 ± 1.3) volunteers were studied cross‐sectionally. Thirty‐five of the subjects were also reevaluated after 1.5 years on a weight reduction program entailing dieting and exercise; changes of serum resistin were compared with changes of BMI, body composition, fat distribution, and several indices of insulin sensitivity derived from plasma glucose and serum insulin levels measured during 75‐g oral glucose tolerance test. Results: In a cross‐sectional analysis, serum resistin was significantly higher in obese subjects than in lean volunteers (24.58 ± 12.93 ng/mL; n = 64 vs. 12.83 ± 8.30 ng/mL; n = 15; p < 0.01), and there was a correlation between resistin level and BMI, when the two groups were combined (ρ = 0.35, p < 0.01). Although cross‐sectional analysis in obese subjects revealed no correlation between serum resistin and parameters related to adiposity or insulin resistance, longitudinal analysis revealed change in serum resistin to be positively correlated with changes in BMI, body fat, fat mass, visceral fat area, and mean glucose and insulin (ρ = 0.39, 0.40, 0.44, 0.50, 0.40, and 0.50; p = 0.02, 0.03, 0.02, <0.01, 0.02, and <0.01, respectively). Discussion: Resistin appears to be related to human adiposity and to be a possible candidate factor in human insulin resistance.