Possible role of adiponectin and insulin sensitivity in mediating the favorable effects of lower body fat mass on blood lipids.

AIMS: The objective of this study was to investigate the role of insulin sensitivity and serum adiponectin concentration as determinants, in middle-aged men, of the relationship between lower body fat and blood lipids after truncal fat has been accounted for. METHODS: Men (443) aged 39-65 yr, body mass index 18-43 kg/m(2), participated in the study. The following variables were measured: regional body fat distribution as assessed by dual-energy x-ray absorptiometry, maximal oxygen uptake, physical activity, fasting levels of serum adiponectin, triglycerides, and high-density lipoprotein- and total cholesterol. Plasma glucose and serum insulin were measured in the fasting state and after an oral glucose load. RESULTS: Lower body fat mass was inversely associated with serum triglycerides and total cholesterol and positively with serum high-density lipoprotein-cholesterol after adjustment for age, lean tissue mass, truncal fat mass, weight history, maximal oxygen uptake, and the level of physical activity (P < 0.0005). Serum adiponectin level and Matsudas insulin sensitivity index were positively intercorrelated, and both were positively correlated to lower body fat mass. When including adiponectin and insulin sensitivity in the analyses, the relationships between lower body fat mass and serum lipids were partly explained. CONCLUSION: For a given level of truncal fat mass, a large lower body fat mass is associated with an advantageous blood lipid profile, which may be partially mediated by the relationships to both insulin sensitivity and serum adiponectin level.

The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women.

Twenty-four-hour energy expenditure and substrate use were measured by indirect calorimetry in respiration chambers on a fixed physical program and related to body composition and plasma concentrations of various substrates and thermogenic hormones. Fifty premenopausal women with a wide range of body weight were examined in the follicular menstrual phase under weight stable conditions. Most of the variance in the sleeping energy expenditure (82%) was accounted for by two covariates, lean body mass (75%, P less than 0.0001), and fat mass (7%, P less than 0.0001). An additional 6% of the variance in sleeping energy expenditure was accounted for by plasma androstenedione concentration (4%, P = 0.0005) and by free T3 index (2%, P = 0.03). Thus physiological variation among individuals in plasma androstenedione concentration may result in a difference in energy expenditure of 908 kJ/day and the corresponding variation in free T3 index may result in a difference between individuals of 594 kJ/day. Fifty four percent of the variation in carbohydrate oxidation rates was accounted for by 24-h energy balance, and by plasma concentrations of insulin, nonesterified fatty acids, and estradiol. Waist circumference, plasma nonesterified fatty acids, and estradiol concentrations explained 49% of the variance in 24-h lipid oxidation. An obese subgroup of women (n = 27) had significantly higher 24-h energy expenditure, lipid, and carbohydrate oxidation rates than an age-matched normal weight group (n = 16), but the entire group difference in energy expenditure was explained by differences in body composition. We conclude that physiological variations in plasma androstenedione and T3 concentrations contribute to the interindividual variance in energy expenditure of women, and their role is not different in obese women. A positive energy balance and increased insulin action may be mediators of the higher carbohydrate oxidation in obesity, whereas an increased substrate availability seems to bring about the increased lipid oxidation.

Twenty-four-hour energy expenditure and substrate utilization in body builders.

Twenty-four--hour energy expenditure (EE) was measured by indirect calorimetry in 10 body builders and 10 lean control subjects of the same sex with similar age, height, and percent body fat. The study was performed to elucidate possible effects of strength training on energy metabolism and substrate utilization. Twenty-four--hour EE was higher in the body builders than in control subjects but was similar when adjusted for differences in fat-free mass. A higher 24-h nonprotein respiratory quotient (RQ) was found in the body builders. Because both groups were in energy balance, the higher RQ in the body builders can be attributed to a different habitual diet or may be explained by physiological differences.

A 24-h energy expenditure study on reduced-obese and nonobese women: effect of beta-blockade.

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were studied in a respiration chamber in 15 reduced-obese (BMI = 24.7) and 8 nonobese (BMI = 20.1) women. Two experiments were performed, one in which beta-blockade was introduced by propranolol and one with placebo. When adjusted for differences in fat-free mass, no difference in 24-h EE was found between the reduced-obese and nonobese groups in placebo experiments. Propranolol reduced 24-h EE by 2.7% in the reduced-obese group whereas no reduction was seen in the nonobese group. A positive correlation was found between fasting glycerol concentration and lipid oxidation. During daytime, lipid oxidation was reduced and carbohydrate oxidation increased by propranolol only in the nonobese subjects. Propranolol reduced fasting glycerol and free fatty acid concentrations in both groups. Beta-blockade seems to have little effect on sedentary 24-h EE but may have a suppressing effect on lipid combustion.

Low resting metabolic rate in subjects predisposed to obesity: a role for thyroid status.

A low resting metabolic rate (RMR) for a given body composition has been identified as a risk factor for weight gain and obesity, and has also been reported in formerly obese individuals with the genetic predisposition for obesity. The possible role of thyroid hormone in low RMR was studied in a large sample of postobese women. RMR was measured by indirect calorimetry in 28 weight-stable postobese women with a family history of obesity (PO group) and in a control group of 28 nonobese women closely matched for age, fat mass, and fat-free mass. RMR was 8% lower in the PO than in the control group [[symbol: see text]; 95% Cl:5856 (5520, 6214) compared with 6408 kJ/d (6096, 6768 kJ/d), P < 0.02], and the group difference remained unchanged after fat-free mass and fat mass were adjusted for (552 kJ/d, P < 0.015). The PO group had lower plasma free triiodothyronine [2.4 (1.9, 3.0) compared with 3.4 pmol/L (2.9, 3.9 pmol/L), P < 0.01], whereas plasma androstenedione only tended to be lower in the PO than in the control group. Adjustment for differences in androstenedione did not reduce the difference in RMR, whereas adjustment for differences in plasma free triiodothyronine eliminated the group difference (96 kJ/d, P = 0.59). The present study shows that RMR for a given body composition is lower among postobese than among matched never-obese control subjects. Statistically, the lower plasma free triiodothyronine concentrations of the postobese subjects could explain their lower RMRs, but it remains to be established whether these findings are causally related.

Obesity as an adaptation to a high-fat diet: evidence from a cross-sectional study.

Expansion of the fat stores has been proposed as a prerequisite for increasing fat oxidation in response to a high-fat diet in individuals with a predisposition to obesity. In a cross-sectional design we measured 24-h substrate oxidations on a standardized diet in 38 overweight or obese and 35 nonobese women. Fat oxidation (g/d) was mainly a function of total energy requirements (r = 0.71, P < 0.0001). To account for this we used for further analysis oxidative fat energy (%), a counterpart to dietary fat energy (%). After differences in fat energy of consumed food (%), age, and 24-h energy balance were adjusted for, obese women had higher oxidative fat energy than did nonobese women [40.2% (37.8-42.6) vs 36.0% (33.6-38.5), P < 0.02]. Adjusted oxidative fat energy (%) increased with increasing size of fat mass (r = 0.31, P < 0.01). This relation suggests that a 10-kg change in fat mass may be caused by a change in dietary fat energy of > or = 1.6% (0.4-2.7%). The study supports the concept that in susceptible individuals the expansion of fat stores is a prerequisite to increase the oxidative fat energy to an amount commensurate with a high percentage of dietary fat energy.

Meta-analysis of resting metabolic rate in formerly obese subjects.

BACKGROUND: A low resting metabolic rate (RMR) for a given body size and composition is partly genetically determined and has been suggested to be a risk factor for weight gain. Moreover, a low relative RMR has been reported in some, but not all, studies of formerly obese persons. The inconsistent reports may be due to a lack of statistical power to detect small differences in RMR and improper adjustment for body size and composition. OBJECTIVE: We conducted a meta-analysis based on published studies of RMR in formerly obese persons [body mass index (in kg/m2) < or = 27] and matched control subjects who had never been obese. DESIGN: We performed both an individual subject data meta-analysis and a traditional meta-analysis. RESULTS: The individual subject data meta-analysis included 124 formerly obese and 121 control subjects. RMR adjusted for differences in fat-free mass and fat mass was 2.9% lower in formerly obese subjects than in control subjects (P = 0.09). A low relative RMR (> 1 SD below the mean of the control group) was found in 3.3% of the control subjects and in 15.3% of the formerly obese subjects [difference: 12% (95% CI: 4.7%, 19.3%); P < 0.003]. The traditional meta-analysis was based on 12 studies (including 94 formerly obese and 99 control subjects) and included 3 studies not represented in the individual subject data analysis. In this analysis, relative RMR was lower in the formerly obese group than in the control group by 5.1% (95% CI: 1.7%, 8.6%). CONCLUSIONS: Formerly obese subjects had a 3-5% lower mean relative RMR than control subjects; the difference could be explained by a low RMR being more frequent among the formerly obese subjects than among the control subjects. Whether the cause of the low RMR is genetic or acquired, the existence of a low RMR is likely to contribute to the high rate of weight regain in formerly obese persons.

Effects of oral D-tagatose, a stereoisomer of D-fructose, on liver metabolism in man as examined by 31P-magnetic resonance spectroscopy.

D-tagatose, which is a stereoisomer of D-fructose, is phosphorylated to D-tagatose-1-phosphate by fructokinase in the liver. Because of a slow degradation rate of D-tagatose-1-phosphate, this substance may accumulate, and ingested D-tagatose may therefore cause a longer lasting reduction in inorganic phosphate (Pi) and adenosine triphosphate (ATP) levels in the liver compared with D-fructose. Similar to what is seen in patients with hereditary fructose intolerance, this may increase purine nucleotide degradation and thereby increase uric acid production. The effect of 30 g D-tagatose or D-fructose administered orally on ketohexose-1-phosphates, ATP, and Pi levels in the liver was studied by 31P-magnetic resonance spectroscopy (PMRS) in 5 young male volunteers. Blood and urine were collected to detect a possible increased uric acid production. A peak at 5.2 ppm assigned as D-tagatose-1-phosphate equivalent to about 1 mmol/L was found in the spectrum within 30 minutes after D-tagatose was administered in all subjects. Concomitantly, ATP was reduced by about 12% (P < .05). Both effects had vanished after 150 minutes. Serum uric acid concentration was increased by 17% 50 minutes after D-tagatose (P < .05) and did not reach baseline level when the experiment was terminated 230 minutes after the load. Although renal fractional extraction of uric acid decreased by approximately 12%, this could not explain the acute hyperuricemic effect of D-tagatose. No changes in 31PMRS spectra or serum uric acid concentration were found after D-fructose. These results suggest that a moderate intake of D-tagatose may affect liver metabolism by phosphate trapping despite the fact that the sugar may only be incompletely absorbed in the gut.

24-hour energy expenditure and substrate oxidation rates are unaffected by body fat distribution in obese women.

Twenty-four-hour energy expenditure (EE) and nonprotein respiratory quotient (RQnp) were measured by indirect calorimetry in 19 upper-body-obese (UBO) and 15 lower-body-obese (LBO) women with similar body mass index (BMI) and body fat percent. The measurements were performed in a respiration chamber on a predetermined physical activity program and a controlled diet. No differences between the UBO and LBO groups were found in 24-hour, daytime, and sleeping EE after adjustment for differences in fat-free mass (FFM). Furthermore, no group effect was observed in RQnp, but a positive correlation was found between RQnp and age. Despite the fact that an increased free fatty acid (FFA) turnover has been found in UBO subjects, the present study does not support the contention that upper-body obesity is accompanied by an increased lipid oxidation.

The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women.

Treatment with beta 2-agonists promotes fat loss and muscle growth in numerous species, but human studies are lacking. We studied the effect of a compound with beta 2-agonistic properties (ephedrine 20 mg/caffeine 200 mg [E + C]). Fourteen obese women were treated with a 4.2-MJ/d diet and either E + C or placebo (P) three times per day for 8 weeks in a double-blind study. Weight-loss was not different in the groups, but the E + C group lost 4.5 kg more body fat and 2.8 kg less fat-free mass (FFM). The decrease in 24-hour energy expenditure (EE) seen in the P group was 10% at day 1 and 13% at day 56, but was only 7% and 8% in the treated group (P = .044). The higher EE in the E +C group was entirely covered by fat oxidation. These findings provide evidence that promotion of fat loss and preservation of FFM during weight reduction may also be achieved pharmacologically in humans.

D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration.

D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.

Reproducibility of 24-h energy expenditure and macronutrient oxidation rates in an indirect calorimeter.

The maintenance of weight and adipose tissue mass in humans appears to be related to a balance between the rates of oxidation and consumption of macronutrients; yet, little evidence is available on the reproducibility of 24-h macronutrient oxidation rates and how this relates to diet in the days preceding a chamber session. This study examined the reproducibility of 24-h macronutrient oxidation rates, 24-h energy expenditure (EE), and respiratory quotient (RQ) in 30 adults who ate their habitual diets before two 24-h whole body indirect calorimeter sessions. Results showed that the within-subject coefficients of variation (CVws) for 24-h EE and RQ were 2.8 and 2.6%, respectively. CVws for macronutrient oxidations ranged from approximately 15 to 25%. Means comparisons of 24-h EE, RQ, and macronutrient oxidation rates between sessions showed no significant differences, and all variables had significant positive intraclass correlation coefficients (P < 0.05). In conclusion, macronutrient oxidations all showed significant reproducibility for the group and a significant but lower reproducibility for individuals when habitual diet and activity preceded the experimental sessions.

Effects of exercise training on abdominal obesity and related metabolic complications.

Excessive deposition of visceral adipose tissue is known to predispose to cardiovascular diseases. Considerable epidemiological and experimental evidence suggests that many physiological factors are involved in the aetiology of premature atherosclerosis associated with visceral obesity. Insulin resistance is frequently associated with abdominal obesity, and probably plays an important role in the pathophysiology of hypertriglyceridaemia, low levels of plasma high-density lipoprotein (HDL)-cholesterol, hypertension and reduced fibrinolytic activity. Exercise training may counteract the aberrant metabolic profile associated with abdominal obesity both directly and as a consequence of body fat loss. Exercise may increase insulin sensitivity, favourably alter the plasma lipoprotein profile and improve fibrinolytic activity. Changes in the activity of insulin-sensitive glucose transporters and of skeletal muscle lipoprotein lipase are some of the possible explanations for the increased insulin sensitivity and improved blood lipid profile associated with regular exercise. This review presents physical training as a relevant nonpharmacological tool in the treatment of abdominal obesity and associated metabolic disorders. The impact of regular exercise on the different aspects of the insulin resistance syndrome is discussed. The roles of gender, age and the state of insulin resistance on the metabolic effect of physical training are also considered.

Body fatness in active individuals reporting low lipid and alcohol intake.

OBJECTIVES: To evaluate body fatness in subjects complying with common public health guidelines for lipid and alcohol intake as well as physical activity participation. SUBJECTS: A sample of 358 male subjects who participated in phase 1 of the Quebec Family Study. DESIGN: The association between adiposity, lipid and alcohol intake and physical activity participation was analyzed in the overall sample. A comparison of body fatness in individuals adhering or not to public health recommendations was also performed. RESULTS: Significant positive correlations were observed between the percentage of dietary energy as lipid and adiposity indicators. Accordingly, subjects classified as low-fat consumers displayed significantly lower levels of fat mass and subcutaneous adiposity compared to high-fat consumers. When subjects reporting low lipid and alcohol intake and regular participation in vigorous physical activities were compared to those exhibiting opposite behaviors, the between-group difference in subcutaneous adiposity was doubled and this was essentially explained by an increase in the difference for truncal subcutaneous adiposity. CONCLUSION: These results indicate that the adherence to a lifestyle characterized by high-fat and alcohol intake as well as sedentariness promotes fat gain, particularly in the trunk area.

Effects of trans- and n-3 unsaturated fatty acids on cardiovascular risk markers in healthy males. An 8 weeks dietary intervention study.

BACKGROUND: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable. OBJECTIVE: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA. DESIGN: Randomized, double-blind, parallel intervention trial. SETTING: Department of Human Nutrition, The Royal Veterinary and Agricultural University. SUBJECTS: In all, 87 healthy males included, 79 completed. INTERVENTION: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention. RESULTS: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged. CONCLUSION: The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers. SPONSORSHIP: Danish Medical Research Council (Grant no. 22-01-0390), Center of Advanced Food Research (Copenhagen, Denmark) (Grant no. KVL-R-2001-107), the Danish Heart Association (Grant no. 99-2-3-45-22748), Novozymes (Bagsvaerd, Denmark), Aarhus Olie (Aarhus, Denmark), and from private sources. The experimental fats were provided by Pronova Biocare (Aalesund, Norway) and Aarhus Olie (Aarhus, Denmark).

[Effect of 3-month exercise training on daily energy expenditure in formerly obese women with reduced and stable weight]. / Effekt af tre måneders konditionstraening på døgnenergiomsaetningen hos vaegtstabile reduceret obese kvinder.

Predisposition to obesity has been suggested to be related to a low energy expenditure (EE). This condition could be counteracted by physical exercise. In the present study we wanted to elucidate if aerob training could increase sedentary 24-hour energy expenditure in formerly obese subjects. Seven reduced-obese premenopausal women were studied in a respiration chamber before and after a three month period of aerobic training. No significant effects of training were seen on daytime, sleeping or total 24-hour EE. However, the change in daytime EE was positively correlated to the change in VO2max. Sleeping and 24-hour respiratory quotients were slightly increased after the training period. In order to reveal a possible role of the sympathetic nervous system in the observed effect of training, additional experiments were performed with beta blockade. However, no interactions between training and beta blockade were found.

[The "Lundberg cure"--an ineffective weight loss regimen. Study of the increase in metabolic rate supposedly induced by the "Lundberg cure"]. / "Lundbergkuren"--en affedningskur med ringe virkning. En undersøgelse af "Lundbergkuren"s påståede haevning af stofskiftet.

A recently marketed training principle, the "Lundberg" cure was postulated to cause an extraordinary weight loss when practised for only seven minutes per day. One hour of intensive training should lead to an additional energy expenditure of approx. 500 kcal. If the "Lundberg" cure was intensive, the treatment would mean a weight loss of approx. 240 g/mo. By testing the principle using respiratory chambers, it was shown that the metabolism was unchanged after the training period and that the additional energy expenditure during training averaged 0.94 kJ/kg lean body mass (SEM 0.07) corresponding to 63 g fat tissue/month or half a slice of white bread a day. It is concluded that the "Lundberg" cure, if practised as described in the press, will not lead to any weight loss, apart from that expected from the physical activity.

[Low energy metabolism in persons predisposed to obesity: significance of the thyroid status]. / Lav energiomsaetning hos personer disponeret for fedme: betydning af thyreoideastatus.

A low resting metabolic rate (RMR) for a given body composition has been identified as a risk factor for weight gain and obesity, and has also been reported in formerly obese individuals with the genetic predisposition to obesity. The possible role of thyroid hormone in low RMR was studied in a large sample of postobese women. RMR was measured by indirect calorimetry in 28 weight-stable postobese women with a family history of obesity (PO group) and in a control group of 28 nonobese women closely matched for age, fat mass, and fat-free mass. RMR was 8% lower in the PO than in the control group (95% CI: 5856 kJ/d [5520-6214] vs 6408 kJ/d [6096-6768]), (p < 0.02). The group difference remained unchanged after fat-free mass and fat mass were adjusted for (552 kJ/d, p < 0.015). The PO group had lower plasma free triiodothyronine: 2.4 (1.9-3.0) compared with 3.5 pmol/l (2.9-3.9), (p < 0.01), whereas plasma androstenedione only tended to be lower in the PO. Adjustment for differences in androstenedione did not reduce the difference in RMR, whereas adjustment for differences in plasma free triiodothyronine eliminated the group difference (96 kJ/d, p = 0.59). The present study shows that RMR for a given body composition is lower among postobese than among matched never-obese control subjects. Statistically the lower plasma free triiodothyronine concentration of the postobese subjects could explain their lower RMRs, but it remains to be established whether these findings are causally related.

[Prognostic markers for weight loss in the treatment of obesity]. / Prognostiske markører for vaegttab ved adipositasbehandling.

The aim of the study was to identify prognostic metabolic markers for long-term weight loss outcome in obese women. Forty female obese patients underwent a dietary intervention of 36 weeks treatment with a 4.2 MJ/d low-fat high carbohydrate diet and were followed-up two and a half years after cessation of treatment. The maximum weight loss (mean 16.2 kg. 95% CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure (EE) (p < 0.01), fat oxidation (%) (p < 0.02), plasma dihydrotestosterone (DHT) (p < 0.01), and to postprandial noradrenaline concentration (p < 0.04). Together these factors could explain 41% of the variation in maximum weight loss. After 36 weeks only 24-h EE and DHT had predictive power on weight loss. Weight losses in upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (p < 0.02) and the adjusted relative risk of losing < 10 kg in the upper compared to the lower DHT tertile was 12% (4-32%). At two and a half years follow-up 21 patients had maintained some of the weight loss (54%), while 14 patients had maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also associated with better weight loss at two and a half years follow-up. The study suggests that long-term weight loss outcome may be predicted by pre-treatment metabolic and hormonal factors in obese women.

[Objective assessment of the habitual dietary fat content in patients with obesity]. / Objektiv bestemmelse af den habituelle kosts fedtindhold hos patienter med adipositas.

A diet rich in fat may be an important precipitating factor of obesity, but studies on this relation have been hampered by the lack of an objective method to assess habitual dietary fat content. We measured 24-h fat oxidation in a respiration chamber in 38 overwight or obese and 35 nonobese women, and used it as an estimate of habitual dietary fat energy (%). After adjustment for confounders, obese women had higher oxidative fat energy than nonobese women [40.2% (37.8-42.6) vs. 36.0% (33.6-38.5), p < 0.02]. Adjusted oxidative fat energy (%) increased with increasing size of fat mass, and this relation suggest that a 10-kg change in fat mass may be caused by a change in dietary fat energy of > or = 1.6%. This objective assessment supports the contention that obese subjects consume a diet with a higher fat content than nonobese individuals, and the high-fat diet may have causal importance for the development and maintenance of obesity.