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1.  Systemic β-Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans 
Diabetes  2012;61(12):3106-3113.
Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by β-adrenergic agonists, at least in animals. However, the exact role of the β-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography imaging in 10 lean men during systemic infusion of the nonselective β-agonist isoprenaline (ISO) and compared this with cold-activated BAT activity. ISO successfully mimicked sympathetic stimulation as shown by increased cardiovascular and metabolic activity. Energy expenditure increased to similar levels as during cold exposure. Surprisingly, BAT was not activated during β-adrenergic stimulation. We next examined whether the high plasma free fatty acid (FFA) levels induced by ISO competed with glucose ([18F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI). ACI successfully lowered plasma FFA, but did not increase [18F]FDG-uptake in BAT. We therefore conclude that systemic nonselective β-adrenergic stimulation by ISO at concentrations that increase energy expenditure to the same extent as cold exposure does not activate BAT in humans, indicating that other tissues are responsible for the increased β-adrenergic thermogenesis.
doi:10.2337/db12-0288
PMCID: PMC3501890  PMID: 22872233
2.  Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance 
The New England journal of medicine  2010;363(22):2102-2113.
Background
Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power.
Methods
We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet.
Results
A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein–high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P = 0.02 and P = 0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein–high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P = 0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P = 0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events.
Conclusions
In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss. (Funded by the European Commission; ClinicalTrials.gov number, NCT00390637.)
doi:10.1056/NEJMoa1007137
PMCID: PMC3359496  PMID: 21105792
4.  Starches, Sugars and Obesity 
Nutrients  2011;3(3):341-369.
The rising prevalence of obesity, not only in adults but also in children and adolescents, is one of the most important public health problems in developed and developing countries. As one possible way to tackle obesity, a great interest has been stimulated in understanding the relationship between different types of dietary carbohydrate and appetite regulation, body weight and body composition. The present article reviews the conclusions from recent reviews and meta-analyses on the effects of different starches and sugars on body weight management and metabolic disturbances, and provides an update of the most recent studies on this topic. From the literature reviewed in this paper, potential beneficial effects of intake of starchy foods, especially those containing slowly-digestible and resistant starches, and potential detrimental effects of high intakes of fructose become apparent. This supports the intake of whole grains, legumes and vegetables, which contain more appropriate sources of carbohydrates associated with reduced risk of cardiovascular and other chronic diseases, rather than foods rich in sugars, especially in the form of sugar-sweetened beverages.
doi:10.3390/nu3030341
PMCID: PMC3257742  PMID: 22254101
starch; sugars; obesity; metabolic syndrome; insulin resistance; lipids; hormones; energy intake; energy expenditure; satiety
5.  Dietary Protein and Blood Pressure: A Systematic Review 
PLoS ONE  2010;5(8):e12102.
Background
Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP.
Methodology/Principal Findings
We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein.
Conclusions/Significance
In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroups.
doi:10.1371/journal.pone.0012102
PMCID: PMC2920332  PMID: 20711407
6.  Changes in skinfold thickness and waist circumference after 12 and 24 months resulting from the NHF-NRG In Balance-project 
Background
More knowledge is needed regarding the effectiveness of weight gain prevention programmes. The present study tested the 12-and 24-month effectiveness of the 'Netherlands Research programme weight Gain prevention' (NHF-NRG)-In Balance-project, a worksite-based intervention aimed at the prevention of weight gain.
Methods
Twelve worksites (n = 553 participants) were matched and assigned to either intervention or control group. The worksites and employees of the intervention group received individual (i.e. pedometer, computer-tailored advice) and environmental (i.e. changes in worksite canteen) interventions, directed at physical activity and food intake over 1-year. Differences between the intervention and control group in changes in body weight, BMI, skinfold thickness and waist circumference at 12 and 24 months were examined using multilevel linear regression analyses adjusting for various baseline characteristics (age, gender, BMI, marital status, education and smoking status).
Results
A significant greater reduction in skinfold thickness was found in the intervention group than in the control group, both after 12-and 24 months (Unstandardized regression coefficients (B) = -2.52, 95% C.I. -4.58, -0.45; p = 0.018; B = -4.83, 95% C.I. 6.98, -2.67; p < 0.001 respectively). Significant differences were also observed for changes in waist circumferences both at 12 months (B = -1.50, 95% C.I. -2.35, -0.65; p < 0.001) and at 24 months (B = -1.30, 95% C.I. -2.18, -0.42; p = 0.005). No significant changes were observed for weight and BMI.
Conclusions
The project was effective with regard to changes in skinfold thickness and waist circumference both at 12 and 24 months. It supports the usefulness of worksite-based prevention, especially regarding maintenance of behavioral changes.
doi:10.1186/1479-5868-7-26
PMCID: PMC2858095  PMID: 20370934
7.  Hormone-Sensitive Lipase Serine Phosphorylation and Glycerol Exchange Across Skeletal Muscle in Lean and Obese Subjects  
Diabetes  2008;57(7):1834-1841.
OBJECTIVE—Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or β-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity.
RESEARCH DESIGN AND METHODS—Forearm skeletal muscle lipolysis was investigated in 13 lean and 10 obese men using [2H5]glycerol combined with the measurement of arteriovenous differences before and during β-adrenergic stimulation using the nonselective β-agonist isoprenaline (ISO). Muscle biopsies were taken from the vastus lateralis muscle before and during ISO to investigate hormone-sensitive lipase (HSL) protein expression and serine phosphorylation.
RESULTS—Baseline total glycerol release across the forearm was significantly blunted in obese compared with lean subjects (P = 0.045). This was accompanied by lower HSL protein expression (P = 0.004), HSL phosphorylation on PKA sites Ser563 (P = 0.041) and Ser659 (P = 0.09), and HSL phosphorylation on the AMPK site Ser565 (P = 0.007), suggesting a blunted skeletal muscle lipolysis in obesity. Total forearm glycerol uptake during baseline did not differ significantly between groups, whereas higher net fatty acid uptake across the forearm was observed in the obese (P = 0.064). ISO induced an increase in total glycerol release from skeletal muscle, which was not significantly different between groups. Interestingly, this was accompanied by an increase in HSL Ser659 phosphorylation in obese subjects during ISO compared with baseline (P = 0.008).
CONCLUSIONS—Obesity is accompanied by impaired fasting glycerol release, lower HSL protein expression, and serine phosphorylation. It remains to be determined whether this is a primary factor or an adaptation to the obese insulin-resistant state.
doi:10.2337/db07-0857
PMCID: PMC2453623  PMID: 18398140
8.  Adipose triglyceride lipase (ATGL) expression in human skeletal muscle is type I (oxidative) fiber specific 
Histochemistry and Cell Biology  2008;129(4):535-538.
Accumulation of triacylglycerol (TAG) and lipid intermediates in skeletal muscle plays an important role in the etiology of insulin resistance and type 2 diabetes mellitus. Disturbances in skeletal muscle lipid turnover and lipolysis may contribute significantly to this. So far, knowledge on the regulation of muscle lipolysis is limited. Recently the identification of a new lipase was reported: adipose triglyceride lipase (ATGL). ATGL deficient animals show significant lipid accumulation in skeletal muscle, which may indicate that ATGL plays a pivotal role in skeletal muscle lipolysis. However, until now, it is still unknown whether ATGL protein is expressed in human skeletal muscle. Therefore, the aim of the present study was to investigate whether ATGL is expressed at the protein level in human skeletal muscle, and to examine whether its expression is fiber-type specific. To accomplish this, we established an imunohistochemical and immunofluorescent staining procedure to study ATGL protein expression in relation to fiber type in human vastus lateralis muscle of eight male subjects (BMI range: 21.0–34.5 kg/m2 and age: 38–59 years). In the present paper we report for the first time that ATGL protein is indeed expressed in human skeletal muscle. Moreover, ATGL is exclusively expressed in type I (oxidative) muscle fibers, suggesting a pivotal role for ATGL in intramuscular fatty acid handling, lipid storage and breakdown.
doi:10.1007/s00418-008-0386-y
PMCID: PMC2668625  PMID: 18224330
ATGL;  Skeletal muscle; Fiber type; Obesity; Protein
9.  Caloric Restriction Induces Changes in Insulin and Body Weight Measurements That Are Inversely Associated with Subsequent Weight Regain 
PLoS ONE  2012;7(8):e42858.
Background
Successful weight maintenance following weight loss is challenging for many people. Identifying predictors of longer-term success will help target clinical resources more effectively. To date, focus has been predominantly on the identification of predictors of weight loss. The goal of the current study was to determine if changes in anthropometric and clinical parameters during acute weight loss are associated with subsequent weight regain.
Methodology
The study consisted of an 8-week low calorie diet (LCD) followed by a 6-month weight maintenance phase. Anthropometric and clinical parameters were analyzed before and after the LCD in the 285 participants (112 men, 173 women) who regained weight during the weight maintenance phase. Mixed model ANOVA, Spearman correlation, and linear regression were used to study the relationships between clinical measurements and weight regain.
Principal Findings
Gender differences were observed for body weight and several clinical parameters at both baseline and during the LCD-induced weight loss phase. LCD-induced changes in BMI (Spearman’s ρ = 0.22, p = 0.0002) were inversely associated with weight regain in both men and women. LCD-induced changes in fasting insulin (ρ = 0.18, p = 0.0043) and HOMA-IR (ρ = 0.19, p = 0.0023) were also associated independently with weight regain in both genders. The aforementioned associations remained statistically significant in regression models taking account of variables known to independently influence body weight.
Conclusions/Significance
LCD-induced changes in BMI, fasting insulin, and HOMA-IR are inversely associated with weight regain in the 6-month period following weight loss.
doi:10.1371/journal.pone.0042858
PMCID: PMC3414506  PMID: 22905179
10.  Blood Profile of Proteins and Steroid Hormones Predicts Weight Change after Weight Loss with Interactions of Dietary Protein Level and Glycemic Index 
PLoS ONE  2011;6(2):e16773.
Background
Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.
Objective
To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.
Design
Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured.
Results
Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%.
Conclusions
A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss.
Registration
ClinicalTrials.gov NCT00390637
doi:10.1371/journal.pone.0016773
PMCID: PMC3038864  PMID: 21340022

Results 1-10 (10)