Associations between weight loss history and factors related to type 2 diabetes risk in the Stop Diabetes study.

BACKGROUND: Frequent weight loss attempts are related to maladaptive eating behaviours and higher body mass index (BMI). We studied associations of several type 2 diabetes (T2D) risk factors with weight loss history, defined as the frequency of prior weight loss attempts, among Finnish adults at increased risk for T2D. METHODS: This study (n = 2684, 80% women) is a secondary analysis of the 1-year StopDia lifestyle intervention with digital intervention group, digital intervention + face-to-face counselling group, or control group. The frequency of prior weight loss attempts was categorized into five groups: no attempts/no attempts to lose weight, but trying to keep weight stable/1-2 attempts/3 or more attempts/ continuous attempts. Data on emotional eating and social/emotional nutrition self-efficacy were collected with a digital questionnaire. We assessed baseline differences between categories of weight loss history as well as the intervention effects. RESULTS: Altogether 84% of participants had attempted weight loss. Those with one or more weight loss attempts had higher BMI, larger waist circumference, and more emotional eating compared to 'no attempts' and 'no attempts to lose weight, but trying to keep weight stable' categories. The 'no attempts' category had the highest baseline fasting insulin, whereas it showed the largest decrease in this measure with the intervention. This change in fasting insulin in the 'no attempts' category was significantly different from all the other categories. Emotional nutrition self-efficacy slightly improved in the 'no attempts' category, which was significantly different from its concomitant decrease in the categories '1-2 attempts' and '3 or more attempts'. The intervention group assignment did not affect the results. CONCLUSIONS: Multiple attempts to lose weight may unfavourably affect T2D risk factors as well as lifestyle intervention outcomes. More research is needed on how weight loss frequency could affect T2D risk factors and how to design lifestyle interventions for individuals with frequent previous weight loss attempts.

Theory-informed nutrition education curriculum Tools For Feeling Good promotes healthy eating patterns among fifth grade pupils: cross-sectional study.

BACKGROUND: The eating patterns of school-aged children rarely meet recommendations: meal frequency is irregular and the consumption of vegetables is lower and sugar-sweetened products higher than recommended. Although school is an excellent arena for nutrition education to support pupils eating patterns, teachers usually lack efficient tools. The present study aimed to develop a curriculum for nutrition education to be used by teachers and to examine its efficacy in the school environment with respect to the eating patterns of pupils. METHODS: The curriculum was developed in collaboration with school teachers using self-determination theory as a theoretical standpoint. The Health at Every Size concept and sensory-based food education were utilised in the curriculum. Self-reported questionnaires were used to assess the feasibility and impact of the curriculum. Fourteen teachers implemented the curriculum during 2012-2013 with 194 pupils aged 10-13 years (fifth and sixth grades). The control schools included 140 pupils of the same age not following the curriculum. RESULTS: The teachers reported that the curriculum was easy to integrate in the school environment. The fifth graders improved their breakfast frequency, increased their consumption of vegetables and reduced their consumption of ice cream, sweets and sugar-sweetened drinks. No improvement was found in the fifth graders at the control schools. In the sixth graders, no dietary changes were detected in the intervention or control schools. CONCLUSIONS: The pupils in the fifth grade appeared to comprise a responsive target group for nutrition education at schools. The curriculum offers a promising approach for developing healthy eating patterns among fifth graders. Collaboration with teachers in developing the curriculum likely enhanced its feasibility and teacher commitment for implementation.

Eating behaviour is associated with eating frequency and food consumption in 6-8 year-old children: The Physical Activity and Nutrition in Children (PANIC) study.

The association between eating behaviour and dietary factors has been studied narrowly in children. Therefore, we investigated whether eating frequency and food consumption are influenced by eating behaviour in a population sample of 406 children aged 6-8 years. We assessed features of eating behaviour by the Children's Eating Behaviour Questionnaire and dietary factors by a 4-day food record. The results showed that enjoyment of food was directly associated with a number of main meals (p = 0.041) and consumption of vegetables (p = 0.041), cheese (p = 0.005), and meat (p = 0.002). Food responsiveness was directly associated with consumption of fruit and berries (p = 0.013) and meat (p = 0.016). Desire to drink was directly associated with consumption of fat-containing milk (p = 0.002) and inversely associated with consumption of skimmed milk (p = 0.001). Food fussiness was inversely associated with a number of main meals (p = 0.013) and consumption of vegetables (p < 0.001), cheese (p = 0.001), and meat (p = 0.027). Satiety responsiveness was inversely associated with consumption of vegetables (p = 0.031), cheese (p = 0.010), and meat (p < 0.001) and directly associated with consumption of candies and chocolate (p = 0.026). Slowness in eating was inversely associated with consumption of meat (p = 0.018). Where sex differences existed the associations tended to be observed mostly in girls but not in boys. Our study shows that enjoyment of food and food responsiveness are directly associated with consumption of protein-rich foods and vegetables, fruit and berries, whereas food fussiness and satiety responsiveness are inversely associated with consumption of these foods. Assessment of eating behaviour can help in identifying children with various dietary needs.

Determinants of a regular intake of a nutritionally balanced school lunch among 10-17-year-old schoolchildren with special reference to sense of coherence.

BACKGROUND: Free nutritionally balanced school lunches are offered to all schoolchildren in basic education in Finland in each school day. Having school lunch on a regular basis has been found to reflect overall eating patterns. However, skipping part of or even the entire lunch is common. The present study investigated the determinants of the regular consumption of a nutritionally balanced school lunch among schoolchildren, with special reference to the role of sense of coherence (SOC). METHODS: In total, 887 children (457 girls and 424 boys), aged 10-17 years from three municipalities in Eastern Finland, filled in a web-based questionnaire in class during a school day and reported eating patterns, body height and weight and perception of body image. SOC was measured by using the 13-item scale. The statistical analysis was carried out with logistic regression modelling and the chi-squared test. RESULTS: In addition to female gender, frequent shared family meals, perception of body image as appropriate and younger age, SOC was a significant determinant of regularly eating a nutritionally balanced school lunch in the final multivariate modelling. Strong SOC was also associated with more regular meal frequency and health-promoting snack choices. CONCLUSIONS: To promote healthy eating patterns among school-aged children, special attention should be paid to children with weak SOC because they may need specific support and encouragement. They might lack sufficient belief in their own capability and/or do not have adequate support from their family to influence their eating and other lifestyle patterns.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Semisolid meal enriched in oat bran decreases plasma glucose and insulin levels, but does not change gastrointestinal peptide responses or short-term appetite in healthy subjects.

BACKGROUND AND AIMS: Dietary fibre (DF) may play an important role in weight control. The amount, type and way of processing of DF modify food structure and subsequent postprandial appetitive, metabolic and hormonal effects, but current understanding about the magnitude of effects that specific types and amounts of DF exert are still poorly understood. METHODS AND RESULTS: We investigated the effects of wheat and oat brans alone and as combination in semisolid food matrix on postprandial appetite profile and gastrointestinal (GI) hormonal responses. Twenty healthy, normal-weight subjects (5 male/15 female, aged 23.3 ± 0.85y) participated in the study. Isoenergetic and isovolumic (1250 kJ, 300 g) puddings with different insoluble and soluble DF content were tested in a randomised order: pudding with 1) no added fibre, 2) 10 g wheat bran DF, 3) 10 g oat bran DF and 4) combination including 5 g wheat bran DF + 5 g oat bran DF. Blood samples were drawn before and 15, 30, 45, 60, 90, 120 and 180 min after the test meals to determine plasma glucose, ghrelin, peptide YY (PYY) and serum insulin concentrations. Subjective profiles of appetite were assessed using visual analogue scales (VAS). Plasma glucose (P = 0.001) and serum insulin (P < 0.001) responses were the lowest after the pudding with the greatest amount of ß-glucan. In contrast, postprandial ghrelin or PYY responses or appetite sensations did not differ among the meals. CONCLUSION: Oat ß-glucan decreased postprandial plasma glucose and serum insulin responses, yet had no significant effects on GI peptide responses or appetite ratings.

Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome.

BACKGROUND AND AIMS: Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss. METHODS AND RESULTS: 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods. CONCLUSION: Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans.

Short-term regulation of food intake controls what, when and how much we eat within a single day or a meal. This regulation results from an integrated response to neural and humoral signals that originate from the brain, gastrointestinal (GI) tract and adipose tissue. In the GI tract, multiple sites including the stomach, duodenum, distal small intestine, colon, and pancreas are involved in this process. Ingested food evokes satiety by mechanical stimulation and by release of peptides in the GI tract. The intestine in particular plays a key role in satiety through various peptides secreted in response to food. Many of the intestinal peptides inhibit also gastric emptying thus enhancing gastric mechanoreceptor stimulation. In this review, the current knowledge about the effects of different macronutrients and fibre on the release of GI satiety-related peptides in humans is discussed.

Effects of ageing on serotonin transporters in healthy females.

The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [123I]nor-beta-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [123I]nor-beta-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [123I]nor-beta-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade).

Reduced serotonin transporter binding in binge eating women.

RATIONALE: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. OBJECTIVE: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. METHODS: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-beta-CIT, which specifically labels 5-HT transporters. RESULTS: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1 +/- 0.5 versus 2.9 +/- 0.5, respectively). CONCLUSIONS: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women.

Effect of orlistat treatment on body composition and resting energy expenditure during a two-year weight-reduction programme in obese Finns.

OBJECTIVE: To examine the effect of orlistat (Xenical) treatment on body composition and resting energy expenditure (REE) during a 2 y weight-reduction programme in obese Finns. SUBJECTS: Of initially 96 obese subjects who participated in the weight-reduction programme, those 72 subjects (13 men, 59 women, body mass index (BMI) 35.9 +/- 3.9 kg/m2, age 43.4 +/- 6.0 y, mean +/- s.d.) with the complete set of data for 2 y were included in the study. DESIGN: After a 4-week lead-in period, subjects were randomized with either orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a mildly hypoenergetic balanced diet for 1 y. This was followed by 1 y double-blind period with the subjects within each treatment group re-assigned to receive orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a weight maintenance diet. MEASUREMENTS: Body composition and REE were measured after an overnight fast by a bioelectrical impedance method and indirect calorimeter, respectively. The measurements were performed at the beginning and at 3, 6, 12 and 24 months. RESULTS: During the first year, the orlistat-treated group had greater reduction of body weight and fat mass but not of fat-free mass or REE as compared to placebo. During the second year, orlistat treatment was associated with smaller regain of body weight and fat mass with no significant differences in the changes of fat-free mass or REE as compared to placebo. CONCLUSION: In addition to better weight loss and maintenance of reduced weight, orlistat treatment is associated with beneficial changes in body composition but with no excess decrease in resting energy expenditure as compared to that achieved during placebo with a dietary therapy alone.

Regional cerebral blood flow during exposure to food in obese binge eating women.

Cerebral responses elicited by the sight of food were evaluated in eight obese binge eating, 11 obese and 12 normal-weight non-binge eating women. Regional cerebral blood flow (rCBF) was mapped while the subjects were looking at a picture of a landscape (control) or at a portion of food (food exposure), and was measured by [99mTc]ethyl-cysteine-dimer and single photon emission computed tomography. Exposure to food was associated with different changes in the cerebral blood flow (normalized to mean cerebellar counts) of the right and left hemispheres in the obese binge eating than in the obese or normal-weight non-binge eating women. As compared with the non-binge eating groups, the obese binge eating women had, due to food exposure, a greater increase in the cerebral blood flow in the left than right hemisphere, especially in the frontal and pre-frontal regions. In addition, strong linear correlations were observed in this group between the rCBF of the left frontal and pre-frontal regions and the increase in the feeling of hunger during the exposure to food. Left hemisphere and its frontal and pre-frontal regions could thus play a role in binge eating behavior in humans.

The effect of orlistat on the fatty acid composition of serum lipid fractions in obese subjects.

OBJECTIVE: To determine whether there are any changes in the fatty acid composition of serum triglycerides, cholesterol esters, and phospholipids induced by administration of orlistat three times a day compared with placebo as combined with a low-fat hypocaloric diet. METHODS: After 4 weeks of placebo administration, 75 obese subjects were randomized to receive either one capsule (120 mg) of orlistat or placebo three times a day with meals for 1 year in conjunction with a nutritionally balanced hypocaloric diet. Food records were kept to estimate the nutrient intake. The fatty acid composition of serum lipids were analyzed with gas chromatograph. The molar percentage proportions of fatty acids in serum lipid fractions were calculated. RESULTS: Compared with placebo, there was a significant decrease in the proportion of linoleic acid in triglycerides, cholesterol esters, and phospholipids in the orlistat group, even after the effect of the decrease in the linoleic acid dietary intake (percent of energy), weight change, and gender were taken into account. However, the use of orlistat explained only 9% to 13% of the decrease in the proportion of linoleic acid in serum cholesterol esters, triglycerides, and phospholipids. CONCLUSION: The long-term treatment with orlistat may result in a small decline in the proportion of diet-derived fatty acids in serum lipid fractions when used in conjunction with low-fat diet.

Serum leptin and regional cerebral blood flow during exposure to food in obese and normal-weight women.

Leptin is an adipocyte-derived product of the ob gene thought to be involved in the regulation of eating. Receptors for leptin have been found in multiple regions in the brain. In particular, hypothalamic receptors seem to be of fundamental importance for the biological effects of leptin. However, the association of leptin with cerebral function in humans has not been studied. Therefore, in order to assess the possible functional relationships between leptin and cerebral activity in humans, simultaneous serum leptin and regional cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3-39.1) kg/m2] and 12 normal-weight [BMI 22.2 (20.3-24.6) kg/m2] women during exposure to food. The rCBF measurements were performed by 99mTc-ethyl-cysteine-dimer single photon emission computed tomography. A strong inverse association was observed between the leptin and rCBF of hypothalamus during the exposure to food in the obese (r = -0.73, p = 0.02, n = 10), but not in the normal-weight subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of leptin with cerebral activity could be different in obese and normal-weight women; depressed activity of hypothalamic neurones in response to the high peripheral leptin concentration could be postulated to occur in obese women during exposure to food.

Serum leptin, food intake and preferences for sugar and fat in obese women.

OBJECTIVE: To examine the association of leptin with food intake and preferences for sugar and fat in obese humans. METHOD: Food intake and preferences for sugar and fat were measured in 35 obese women by a four-day food record and three hedonic tests, respectively. RESULTS: High fasting serum leptin concentration adjusted for body fat mass and dietary underreporting was associated with low dietary energy and fat intakes. In addition, trends towards lower preference for chocolate as well as for the taste of high-fat, low-sugar mixture were observed in those with higher leptin concentration. CONCLUSION: High serum leptin concentration could be associated in obese women with lower dietary energy and fat intakes, and possibly with the lower preference for fat. These findings need to be verified in further human studies.

Regional cerebral blood flow during food exposure in obese and normal-weight women.

The cerebral responses elicited by the sight of food and food-related cues are poorly known in humans. Therefore, regional cerebral blood flow (rCBF) was measured during food exposure in 11 obese and 12 normal-weight women. The rCBF was mapped while the subject was looking at a picture of a landscape (control) or at a portion of food (food exposure), and was measured by 99mTc-ethyl-cysteine-dimer single photon emission computed tomography. In the obese women, the rCBF was higher in the right parietal and temporal cortices during the food exposure than in the control condition. In addition, in the obese women the activation of the right parietal cortex was associated with an enhanced feeling of hunger when looking at food. No such changes or associations were seen in the normal-weight women. In conclusion, exposure to food is associated with increases in the rCBF of right parietal and temporal cortices in obese women, but not in normal-weight women.

Serum leptin in obesity is related to gender and body fat topography but does not predict successful weight loss.

OBJECTIVE: Leptin is the product of the ob gene shown to regulate body fat and appetite in mice. It is produced by human adipose tissue also, but its physiological functions in man are poorly known. STUDY DESIGN AND METHODS: We studied serum leptin concentrations in ten obese men and 35 obese women (age and body mass index 42 +/- 7 years and 35.1 +/- 3.6 kg/m2 respectively) before (baseline) and at 17 and 57 weeks during weight loss of 10.9% of the initial weight. RESULTS: Serum leptin concentrations at baseline were 55% higher in women than in men (after adjustment for age and body fat mass, P = 0.002) and remained so during the follow-up. At baseline, serum leptin correlated with fat mass (r = 0.60, P < 0.001) estimated by bioelectrical impedance, and the changes in leptin concentrations from baseline to week 17 correlated with the changes in fat mass (r = 0.73, P < 0.001), but baseline leptin levels were not predictive of the successful weight loss. Leptin concentrations correlated with hip circumference (r = 0.49, P < 0.001 at baseline adjusted for age and sex), but the correlation with waist circumference became evident only during the weight loss (at week 57, r = 0.63, P < 0.001). CONCLUSIONS: Serum leptin concentrations are higher in obese women than in obese men before and during weight loss, but the topography of fat tissue influences serum leptin concentrations. Serum leptin concentrations do not predict the response to weight reduction.

Serum leptin and short-term regulation of eating in obese women.

1. Leptin is generally thought to play a key role in the regulation of eating. However, its real role in human eating behaviour is still poorly known. Therefore, the role of leptin in the regulation of eating was examined in obese binge- and non-binge-eating women during exposure to food and food-related stimuli. 2. Eleven binge- and ten non-binge-eating obese women took part in the study. In addition to serum leptin, serum insulin, non-esterified fatty acids, plasma glucose, salivation, the feeling of hunger and the desire to eat were repeatedly measured during the experiment. 3. Serum leptin levels did not differ between the binge- and non-binge-eating women. Neither were leptin levels associated with the feeling of hunger or the desire to eat food, nor with the amount or composition of food eaten. During food exposure leptin levels did not change, whereas at the same time serum insulin levels increased and serum non-esterified fatty acid levels decreased. The change in salivation during food exposure was inversely associated with the fasting leptin level. 4. This study indicates that serum leptin does not play a role in the regulation of eating in obese women, at least not in the short term. Furthermore, leptin levels are not different in obese binge-eating women as compared with obese non-binge-eating women. Interestingly, high fasting leptin levels may be associated with a decreased salivation response in the presence of food and food-related stimuli.

Subjective and physiological cephalic phase responses to food in obese binge-eating women.

OBJECTIVE: The subjective and physiological cephalic phase reactivity to food was investigated in obese binge-eating women. METHOD: Eleven obese binge-eating women and 10 obese nonbinge-eating women participated in a cephalic phase response test consisting of baseline, anticipation, food exposure, and free eating periods. Serum insulin, free fatty acids, and plasma glucose concentrations as well as salivation, feeling of hunger, and desire to eat were repeatedly measured during the test. RESULTS: During the food exposure, the binge eaters reported more desire to eat than did the nonbinge eaters. No differences were found between the groups in the physiological cephalic phase responses except for the lower salivation in the binge eaters during the food exposure. The amount of food eaten after the food exposure was similar in both groups. DISCUSSION: Binge-eating women are characterized by stronger subjective but not stronger physiological cephalic phase reactivity to food.

Serum leptin in relation to resting energy expenditure and fuel metabolism in obese subjects.

OBJECTIVE: Leptin is the product of ob gene shown to regulate body fat in mice. It is produced by human adipose tissue as well, but its physiological functions in man are not known. We explored if there is a relationship in obese humans with serum leptin and energy and fuel metabolism. DESIGN: Cross-sectional study including 45 obese (10 men, 35 women; age and body mass index: 42 +/- 7 y and 35.1 +/- 3.6 kg/m2, respectively). MEASUREMENTS: Food intake by a four-day-food record, blood samples for serum leptin concentrations and resting energy expenditure by indirect calorimetry. RESULTS: Leptin concentrations showed an inverse association (adjusted for fat mass, age and sex) with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate (r = -0.324, P < 0.05; r = -0.420, P < 0.01; r = 0.478, P = < 0.01, respectively), and interestingly, also with dietary fat intake (unadjusted r = -0.30, P < 0.05). Especially, leptin concentrations were elevated in those with low resting energy expenditure and respiratory quotient (below the median). CONCLUSION: Serum leptin concentrations in obese subjects showed an inverse association with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate. The physiological significance of these associations is unclear at the moment but could indicate that obese subjects show resistance to the actions of leptin also outside the brain in terms of regulating metabolic rate and fuel metabolism.