Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

BACKGROUND: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition. The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). METHODS: 148 subjects (39 men, 109 women), mean ±â€¯SD age: 41 ±â€¯9 year; body mass index (BMI): 31.9 ±â€¯3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters. RESULTS: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. CONCLUSION: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.

Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.

BACKGROUND: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs). METHODS: 148 subjects (39 men, 109 women), mean ±â€¯SD age: 41 ±â€¯9 year; body mass index (BMI): 31.9 ±â€¯3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters. RESULTS: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss. CONCLUSION: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.

Physical activity and weight loss are independent predictors of improved insulin sensitivity following energy restriction.

OBJECTIVE: The role of physical activity and the joint effect with sleep duration on insulin sensitivity (IS) during energy restriction followed by weight maintenance were determined. METHODS: One hundred and two subjects (28 males) (mean ± SD age: 40 ± 9 years; BMI: 31.9 ± 3.0 kg/m(2) ) followed a very-low-energy diet for 8 weeks, followed by a 44-week period of weight maintenance. Body composition (three-compartment model based on body weight, total body water, and body volume), physical activity (accelerometry), sleep (questionnaire, Epworth Sleepiness Scale), and fasting plasma insulin and glucose concentrations were assessed before the diet and at 8, 20, and 52 weeks after the start. RESULTS: Compared to baseline, IS was improved significantly after 8 weeks (P < 0.001) and was higher after 20 weeks (P < 0.001) and 52 weeks (P < 0.05). After 8, 20, and 52 weeks, 23% (P < 0.01), 19% (P < 0.05), and 13% (P < 0.05), respectively, of the variance in IS improvement was explained by weight loss percentage and change in physical activity counts. CONCLUSIONS: Maintaining daily physical activity during energy restriction is as important as weight loss itself in the improvement of IS; there was no additional effect of change in sleep duration. During weight maintenance, improved IS is maintained better if physical activity returns to baseline or higher.

Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with adaptations in energy expenditure.

BACKGROUND: Energy restriction causes adaptations in energy expenditure (total-,TEE; resting-,REE; activity induced-,AEE). OBJECTIVE: To determine if changes in the levels of proteins involved in adipocyte glucose and fatty acid metabolism as indicators for energy deficiency are related to adaptations in energy expenditure during weight loss. METHODS: Forty-eight healthy subjects (18 men, 30 women), mean ± SD age 42 ± 8 y and BMI 31.4 ± 2.8 kg/m(2), followed a very low energy diet for 8 wk. Protein levels of fatty acid binding protein 4 (FABP4), fructose-bisphosphate aldolase C (AldoC) and short chain 3-hydroxyacyl-CoA dehydrogenase (HADHsc) (adipose tissue biopsy, western blot), TEE (doubly labeled water), REE (ventilated hood), and AEE were assessed before and after the 8-wk diet. RESULTS: There was a positive correlation between the decrease in AldoC and the decrease in TEE (R = 0.438, P < 0.01) and the decrease change in AEE (R = 0.439, P < 0.01). Furthermore, there was a negative correlation between the increases in HADHsc and the decrease in REE (R = 0.343, P < 0.05). CONCLUSION: The decrease in AldoC correlated with the decrease in AEE, which may be explained by a decreased glycolytic flux. Additionally, the change in HADHsc, a crucial enzyme for a step in beta-oxidation, correlated with the adaptation in REE. CLINICAL TRIAL REGISTRATION NUMBER: NCT01015508 at clinicaltrials.gov.

Leptin and energy restriction induced adaptation in energy expenditure.

BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis, i.e. a disproportional reduction of resting energy expenditure (REE) a decrease in physical activity and increased movement economy. OBJECTIVE: To determine if energy restriction induced adaptive thermogenesis and adaptations in physical activity are related to changes in leptin concentrations. METHODS: Eighty-two healthy subjects (23 men, 59 women), mean ± SD age 41 ± 8 years and BMI 31.9 ± 3.0 kg/m(2), followed a very low energy diet for 8 weeks with measurements before and after the diet. Leptin concentrations were determined from fasting blood plasma. Body composition was assessed with a three-compartment model based on body weight, total body water (deuterium dilution) and body volume (BodPod). REE was measured (REEm) with a ventilated hood and predicted (REEp) from measured body composition. Adaptive thermogenesis was calculated as REEm/REEp. Parameters for the amount of physical activity were total energy expenditure expressed as a multiple of REEm (PAL), activity-induced energy expenditure divided by body weight (AEE/kg) and activity counts measured by a tri-axial accelerometer. Movement economy was calculated as AEE/kg (MJ/kg/d) divided by activity counts (Mcounts/d). RESULTS: Subjects lost on average 10.7 ± 4.1% body weight (P<0.001). Leptin decreased from 26.9 ± 14.3 before to 13.9 ± 11.3 µg/l after the diet (P<0.001). REEm/REEp after the diet (0.963 ± 0.08) was related to changes in leptin levels (R(2)=0.06; P<0.05). There was no significant correlation between changes in leptin concentrations and changes in amount of physical activity. Movement economy changed from 0.036 ± 0.011 J/kg/count to 0.028 ± 0.010 J/kg/count and was correlated to the changes in leptin concentrations (R(2)=0.07; P<0.05). CONCLUSION: During energy restriction, the decrease in leptin explains part of the variation in adaptive thermogenesis. Changes in leptin are not related to the amount of physical activity but could partly explain the increased movement economy.

Genetic predisposition, dietary restraint and disinhibition in relation to short and long-term weight loss.

BACKGROUND: Interindividual differences in response to weight loss and maintenance thereafter are ascribed to genetic predisposition and behavioral changes. OBJECTIVE: To examine whether body weight and short and long-term body weight loss were affected by candidate single nucleotide polymorphisms (SNPs) and changes in eating behavior or by an interaction between these genetic and behavioral factors. METHODS: 150 healthy subjects (39 males, 111 females) aged 20-50 y with a BMI of 27-38 kg/m(2) followed a very low energy diet for 8-weeks, followed by a 3-month weight maintenance period. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG, PPARD, and PPARGC1A. Changes in eating behavior were determined with the Three Factor Eating Questionnaire. RESULTS: A high genetic predisposition score was associated with a high body weight at baseline and more short-term weight loss. From the six selected obesity-related SNPs, FTO was associated with increased body weight at baseline, and the effect allele of PPARGC1A was positively associated with short-term weight loss, when assessed for each SNP separately. Long-term weight loss was associated with a larger increase in dietary restraint and larger decrease in disinhibition. CONCLUSION: During long-term weight loss, genetic effects are dominated by changes in eating behavior.

Relative shrinkage of adipocytes by paraffin in proportion to plastic embedding in human adipose tissue before and after weight loss.

Adipocyte size is a major modulator of endocrine functioning of adipose tissue and methods allowing accurate determination of adipocyte size are important to study energy metabolism. The aim of this study was to assess the relative shrinkage of adipocytes before and after weight loss by comparing adipose tissue from the same subjects embedded in paraffin and plastic. 18 healthy subjects (5 males and 13 females) aged 20-50 y with a BMI of 28-38 kg/m² followed a very low energy diet for 8 weeks. Adipose tissue biopsies were taken prior to and after weight loss and were processed for paraffin and plastic sections. Parameters of adipocyte size were determined with computer image analysis. Mean adipocyte size was smaller in paraffin compared to plastic embedded tissue both before (66 ± 4 vs. 103 ± 5 µm, P < 0.001) as after weight loss (62 ± 4 vs. 91 ± 5 µm, P < 0.001). Relative shrinkage of adipocytes in paraffin embedded tissue in proportion to plastic embedded tissue was not significantly different before and after weight loss (73 and 69%, respectively). Shrinkage due to the type of embedding of the adipose tissue can be ignored when comparing before and after weight loss. Plastic embedding of adipose tissue provides more accurate and sensitive results.

Concomitant changes in sleep duration and body weight and body composition during weight loss and 3-mo weight maintenance.

BACKGROUND: An inverse relation between sleep duration and body mass index (BMI) has been shown. OBJECTIVE: We assessed the relation between changes in sleep duration and changes in body weight and body composition during weight loss. DESIGN: A total of 98 healthy subjects (25 men), aged 20-50 y and with BMI (in kg/m(2)) from 28 to 35, followed a 2-mo very-low-energy diet that was followed by a 10-mo period of weight maintenance. Body weight, body composition (measured by using deuterium dilution and air-displacement plethysmography), eating behavior (measured by using a 3-factor eating questionnaire), physical activity (measured by using the validated Baecke's questionnaire), and sleep (estimated by using a questionnaire with the Epworth Sleepiness Scale) were assessed before and immediately after weight loss and 3- and 10-mo follow-ups. RESULTS: The average weight loss was 10% after 2 mo of dieting and 9% and 6% after 3- and 10-mo follow-ups, respectively. Daytime sleepiness and time to fall asleep decreased during weight loss. Short (≤7 h) and average (>7 to <9 h) sleepers increased their sleep duration, whereas sleep duration in long sleepers (≥9 h) did not change significantly during weight loss. This change in sleep duration was concomitantly negatively correlated with the change in BMI during weight loss and after the 3-mo follow-up and with the change in fat mass after the 3-mo follow-up. CONCLUSIONS: Sleep duration benefits from weight loss or vice versa. Successful weight loss, loss of body fat, and 3-mo weight maintenance in short and average sleepers are underscored by an increase in sleep duration or vice versa. This trial was registered at clinicaltrials.gov as NCT01015508.

Sleep duration, sleep quality and body weight: parallel developments.

The increase in obesity, including childhood obesity, has developed over the same time period as the progressive decrease in self-reported sleep duration. Since epidemiological studies showed an inverse relationship between short or disturbed sleep and obesity, the question arose, how sleep duration and sleep quality are associated with the development of obesity. In this review, the current literature on these topics has been evaluated. During puberty, changes in body mass index (BMI) are inversely correlated to changes in sleep duration. During adulthood, this relationship remains and at the same time unfavorable metabolic and neuro-endocrinological changes develop, that promote a positive energy balance, coinciding with sleep disturbance. Furthermore, during excessive weight loss BMI and fat mass decrease, in parallel, and related with an increase in sleep duration. In order to shed light on the association between sleep duration, sleep quality and obesity, until now it only has been shown that diet-induced body-weight loss and successive body-weight maintenance contribute to sleep improvement. It remains to be demonstrated whether body-weight management and body composition improve during an intervention concomitantly with spontaneous sleep improvement compared with the same intervention without spontaneous sleep improvement.

Physiological response of adipocytes to weight loss and maintenance.

BACKGROUND: Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain. OBJECTIVE: To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance. METHODS: Twenty-eight healthy subjects (12 males), age 20-50 y, and BMI 28-35 kg/m(2), followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up. RESULTS: A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation. CONCLUSION: Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status. TRIAL REGISTRATION: ClinicalTrials.gov NCT01015508.

Weight loss, weight maintenance, and adaptive thermogenesis.

BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis, ie, a disproportional or greater than expected reduction of resting metabolic rate (RMR). OBJECTIVE: The aim of this study was to investigate whether adaptive thermogenesis is sustained during weight maintenance after weight loss. DESIGN: Subjects were 22 men and 69 women [mean ± SD age: 40 ± 9 y; body mass index (BMI; in kg/m(2)): 31.9 ± 3.0]. They followed a very-low-energy diet for 8 wk, followed by a 44-wk period of weight maintenance. Body composition was assessed with a 3-compartment model based on body weight, total body water (deuterium dilution), and body volume. RMR was measured (RMRm) with a ventilated hood. In addition, RMR was predicted (RMRp) on the basis of the measured body composition: RMRp (MJ/d) = 0.024 × fat mass (kg) + 0.102 × fat-free mass (kg) + 0.85. Measurements took place before the diet and 8, 20, and 52 wk after the start of the diet. RESULTS: The ratio of RMRm to RMRp decreased from 1.004 ± 0.077 before the diet to 0.963 ± 0.073 after the diet (P < 0.001), and the decrease was sustained after 20 wk (0.983 ± 0.063; P < 0.01) and 52 wk (0.984 ± 0.068; P < 0.01). RMRm/RMRp was correlated with the weight loss after 8 wk (P < 0.01), 20 wk (P < 0.05), and 52 wk (P < 0.05). CONCLUSION: Weight loss results in adaptive thermogenesis, and there is no indication for a change in adaptive thermogenesis up to 1 y, when weight loss is maintained. This trial was registered at clinicaltrials.gov as NCT01015508.

Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide YY3-36 concentrations and energy intake.

In rats, oligofructose has been shown to stimulate satiety hormone secretion, reduce energy intake and promote weight loss. The present study aimed to examine the effect of oligofructose supplementation on appetite profiles, satiety hormone concentrations and energy intake in human subjects. A total of thirty-one healthy subjects (ten men and twenty-one women) aged 28 (SEM 3) years with a BMI of 24·8 (SEM 0·3) kg/m(2) were included in a randomised double-blind, cross-over study. The subjects received 10 g oligofructose, 16 g oligofructose or 16 g placebo (maltodextrin) daily for 13 d, with a 2-week washout period between treatments. Appetite profile, active glucagon-like peptide 1 (GLP-1) and peptide YY3-36 (PYY) concentrations and energy intake were assessed on days 0 and 13 of the treatment period. Time × treatment interaction revealed a trend of reduction in energy intake over days 0-13 by oligofructose (P = 0·068). Energy intake was significantly reduced (11 %) over time on day 13 compared with day 0 with 16 g/d oligofructose (2801 (SEM 301) v. 3217 (SEM 320) kJ, P < 0·05). Moreover, energy intake was significantly lower with 16 g/d oligofructose compared with 10 g/d oligofructose on day 13 (2801 (SEM 301) v. 3177 (SEM 276) kJ, P < 0·05). Area under the curve (AUC) for GLP-1 on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose (45 (SEM 4) v. 41 (SEM 3) pmol/l × h, P < 0·05). In the morning until lunch, AUC(0-230 min) for PYY on day 13 was significantly higher with 16 g/d oligofructose compared with 10 g/d oligofructose and placebo (409 (SEM 35) v. 222 (SEM 19) and 211 (SEM 20) pg/ml × h, P < 0·01). In conclusion, 16 g/d and not 10 g/d oligofructose may be an effective dose to reduce energy intake, possibly supported by higher GLP-1 and PYY concentrations.