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1.  Effect of increased protein intake on renal acid load and renal hemodynamic responses 
Physiological Reports  2016;4(5):e12687.
Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high‐protein diets reduce renal function. Effects of acute and 4‐week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy‐nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty‐four‐hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein‐ or maltodextrin‐load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein‐supplemented breakfast than after the maltodextrin‐supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin‐converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function.
PMCID: PMC4823604  PMID: 26997623
Acid load; carbohydrate; glomerular filtration rate; kidney; protein
2.  Variation in extracellular matrix genes is associated with weight regain after weight loss in a sex-specific manner 
Genes & Nutrition  2015;10(6):56.
The extracellular matrix (ECM) of adipocytes is important for body weight regulation. Here, we investigated whether genetic variation in ECM-related genes is associated with weight regain among participants of the European DiOGenes study. Overweight and obese subjects (n = 469, 310 females, 159 males) were on an 8-week low-calorie diet with a 6-month follow-up. Body weight was measured before and after the diet, and after follow-up. Weight maintenance scores (WMS, regained weight as percentage of lost weight) were calculated based on the weight data. Genotype data were retrieved for 2903 SNPs corresponding to 124 ECM-related genes. Regression analyses provided us with six significant SNPs associated with the WMS in males: 3 SNPs in the POSTN gene and a SNP in the LAMB1, COL23A1, and FBLN5 genes. For females, 1 SNP was found in the FN1 gene. The risk of weight regain was increased by: the C/C genotype for POSTN in a co-dominant model (OR 8.25, 95 % CI 2.85–23.88) and the T/C–C/C genotype in a dominant model (OR 4.88, 95 % CI 2.35–10.16); the A/A genotype for LAMB1 both in a co-dominant model (OR 18.43, 95 % CI 2.35–144.63) and in a recessive model (OR 16.36, 95 % CI 2.14–124.9); the G/A genotype for COL23A1 in a co-dominant model (OR 3.94, 95 % CI 1.28–12.10), or the A-allele in a dominant model (OR 2.86, 95 % CI 1.10–7.49); the A/A genotype for FBLN5 in a co-dominant model (OR 13.00, 95 % CI 1.61–104.81); and the A/A genotype for FN1 in a recessive model (OR 2.81, 95 % CI 1.40–5.63). Concluding, variants of ECM genes are associated with weight regain after weight loss in a sex-specific manner.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0506-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4653119  PMID: 26584808
Weight regain; Extracellular matrix; SNPs; Adipocytes
3.  Challenges of a healthy lifestyle for socially disadvantaged people of Dutch, Moroccan and Turkish origin in the Netherlands: a focus group study 
Critical Public Health  2014;25(5):615-626.
Lifestyle interventions often fail to successfully reach individuals with lower socio-economic status (SES), possibly because of the individual behavioural orientation to health behaviour and because limited research has included the target groups’ perspectives in the development of interventions. Certainly, in order to make lifestyle interventions more applicable, target groups’ viewpoints should to be taken into account. In order to tailor an effective lifestyle intervention to groups with lower SES of different ethnic origins, 14 focus group interviews were conducted with Turkish, Moroccan and Dutch male and female groups. The target groups’ responses highlight their viewpoint and their dilemmas with regard to physical activity behaviour and healthy eating. Exploration of the target groups’ behaviour in terms of their own logic revealed three prominent themes. Firstly, some individuals find it difficult to maintain healthy eating habits and regular physical activities, as their concept of a healthy life comprises competing values and activities. Secondly, social norms and social practices of others influence health behaviour. Thirdly, respondents’ answers reflect how they deal with the dilemma of competing values and norms. They use different ways of reasoning to make sense of their own (health) behaviour. Taken together, the results of this study suggest that considering physical activity and eating as collective social practices rather than as determinants of health will provide new opportunities to initiate healthy lifestyles and to make lifestyle interventions more applicable to target groups’ realities.
PMCID: PMC4566895  PMID: 26430295
ethnic minorities; collective lifestyle; lifestyle interventions; the Netherlands; social practice; qualitative research
4.  Olfactory receptor genes cooperate with protocadherin genes in human extreme obesity 
Genes & Nutrition  2015;10(4):16.
Worldwide, the incidence of obesity has increased dramatically over the past decades. More knowledge about the complex etiology of obesity is needed in order to find additional approaches for treatment and prevention. Investigating the exome sequencing data of 30 extremely obese subjects (BMI 45–65 kg/m2) shows that predicted damaging missense variants in olfactory receptor genes on chromosome 1q and rare predicted damaging variants in the protocadherin (PCDH) beta-cluster genes on chromosome 5q31, reported in our previous work, co-localize in subjects with extreme obesity. This implies a synergistic effect between genetic variation in these gene clusters in the predisposition to extreme obesity. Evidence for a general involvement of the olfactory transduction pathway on itself could not be found. Bioinformatic analysis indicates a specific involvement of the PCDH beta-cluster genes in controlling tissue development. Further mechanistic insight needs to await the identification of the ligands of the 1q olfactory receptors. Eventually, this may provide the possibility to manipulate food flavor in a way to reduce the risk of overeating and of extreme obesity in genetically predisposed subjects.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0465-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4420755  PMID: 25943692
Extreme obesity; Genetic predisposition; Olfactory system; Protocadherins
5.  Adapting an effective lifestyle intervention towards individuals with low socioeconomic status of different ethnic origins: the design of the MetSLIM study 
BMC Public Health  2015;15:125.
People with low socioeconomic status (SES) and some ethnic minorities are often underrepresented in lifestyle programmes. Therefore, a lifestyle programme was developed especially targeting these groups. Developing this lifestyle programme and designing an intervention study to test the effectiveness of this programme was an informative process in which several obstacles were encountered and choices had to be made. Study protocols, however, rarely describe these obstacles encountered in the protocol design process, and it is not always clear why researchers made certain choices. Therefore, the aim of this article is to describe both the final MetSLIM study protocol and the considerations and choices made in designing this study protocol.
The developed MetSLIM study has a quasi-experimental design, targeting 30- to 70-year-old adults with an elevated waist circumference, living in deprived neighbourhoods, of Dutch, Turkish or Moroccan descent. The intervention group participates in a 12-month lifestyle programme consisting of individual dietary advice, four group sessions and weekly sports lessons. The control group receives written information about a healthy lifestyle and one group session provided by a dietician. The study contains an elaborate effect, process and economic evaluation. Outcome measures are, among other things, change in waist circumference and the other components of the metabolic syndrome.
Matching the preferences of the target group, such as their preferred setting, has implications for the entire study protocol. The process evaluation of the MetSLIM study will provide insight into the consequences of the choices made in the MetSLIM study protocol in terms of reach, acceptability and delivery of the programme, and the effect and economic evaluation will provide insight into the (cost)effectiveness of the lifestyle programme in order to reduce waist circumference among individuals with low SES of different ethnic origins.
Trial registration
Netherlands Trial Register NTR3721 (since November 27, 2012).
PMCID: PMC4339423  PMID: 25880746
Study protocol; Lifestyle intervention; Health promotion; Socioeconomic status; Ethnic groups
6.  Perceptions on healthy eating, physical activity and lifestyle advice: opportunities for adapting lifestyle interventions to individuals with low socioeconomic status 
BMC Public Health  2014;14:1036.
Individuals with low socioeconomic status (SES) are generally less well reached through lifestyle interventions than individuals with higher SES. The aim of this study was to identify opportunities for adapting lifestyle interventions in such a way that they are more appealing for individuals with low SES. To this end, the study provides insight into perspectives of groups with different socioeconomic positions regarding their current eating and physical activity behaviour; triggers for lifestyle change; and ways to support lifestyle change.
Data were gathered in semi-structured focus group interviews among low SES (four groups) and high SES (five groups) adults. The group size varied between four and nine participants. The main themes discussed were perceptions and experiences of healthy eating, physical activity and lifestyle advice. Interviews were transcribed verbatim and a thematic approach was used to analyse the data.
In general, three key topics were identified, namely: current lifestyle is logical for participants given their personal situation; lifestyle change is prompted by feedback from their body; and support for lifestyle change should include individually tailored advice and could profit from involving others. The perceptions of the low SES participants were generally comparable to the perceptions shared by the high SES participants. Some perceptions were, however, especially shared in the low SES groups. Low SES participants indicated that their current eating behaviour was sometimes affected by cost concerns. They seemed to be especially motivated to change their lifestyle when they experienced health complaints, but were rather hesitant to change their lifestyle for preventive purposes. Regarding support for lifestyle change, low SES participants preferred to receive advice in a group rather than on their own. For physical activities, groups should preferably consist of persons of the same age, gender or physical condition.
To motivate individuals with low SES to change their lifestyle, it may be useful to (visually) raise their awareness of their current weight or health status. Lifestyle interventions targeting individuals with low SES should take possible cost concerns into account and should harness the supportive effect of (peer) groups.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-1036) contains supplementary material, which is available to authorized users.
PMCID: PMC4210550  PMID: 25280579
Socioeconomic status; Perceptions on lifestyle; Physical activity; Healthy eating; Focus groups
7.  24-Hour Glucose Profiles on Diets Varying in Protein Content and Glycemic Index 
Nutrients  2014;6(8):3050-3061.
Evidence is increasing that the postprandial state is an important factor contributing to the risk of chronic diseases. Not only mean glycemia, but also glycemic variability has been implicated in this effect. In this exploratory study, we measured 24-h glucose profiles in 25 overweight participants in a long-term diet intervention study (DIOGENES study on Diet, Obesity and Genes), which had been randomized to four different diet groups consuming diets varying in protein content and glycemic index. In addition, we compared 24-h glucose profiles in a more controlled fashion, where nine other subjects followed in random order the same four diets differing in carbohydrate content by 10 energy% and glycemic index by 20 units during three days. Meals were provided in the lab and had to be eaten at fixed times during the day. No differences in mean glucose concentration or glucose variability (SD) were found between diet groups in the DIOGENES study. In the more controlled lab study, mean 24-h glucose concentrations were also not different. Glucose variability (SD and CONGA1), however, was lower on the diet combining a lower carbohydrate content and GI compared to the diet combining a higher carbohydrate content and GI. These data suggest that diets with moderate differences in carbohydrate content and GI do not affect mean 24-h or daytime glucose concentrations, but may result in differences in the variability of the glucose level in healthy normal weight and overweight individuals.
PMCID: PMC4145294  PMID: 25093276
glycemic index; glycemic load; mean 24-h glucose concentration; glucose variability; continuous glucose monitoring
8.  High frequency of rare variants with a moderate-to-high predicted biological effect in protocadherin genes of extremely obese 
Genes & Nutrition  2014;9(3):399.
Relatively rare variants with a moderate-to-high biological effect may contribute to the genetic predisposition of common disorders. To investigate this for obesity, we performed exome sequencing for 30 young (mean age: 29.7 years) extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m2; m/f = 11/29). Rare variants with a moderate-to-high predicted biological effect were assembled and subjected to functional clustering analysis. It showed that the 55 clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002) higher frequency of rare variants than a set of 325 reference genes. Since the protocadherin genes are expressed in the hypothalamus, we tested another 167 genes related to the function of the hypothalamus, but in those genes, the frequency of rare variants was not different from that of the reference genes. To verify the relation of variation in the protocadherin genes with extreme obesity, we analyzed data from more than 4,000 European Americans present on the Exome Variant Server, representing a sample of the general population. The significant enrichment of rare variants in the protocadherin genes was only observed with the group of extremely obese individuals but not in the “general population”, indicating an association between rare variants in the protocadherin cluster genes and extreme obesity.
PMCID: PMC4026441  PMID: 24682882
Extreme obesity; Genetic variation; Functional clustering analysis; Protocadherins; Neuronal plasticity
9.  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.
PMCID: PMC3501890  PMID: 22872233
10.  Caloric Restriction Induces Changes in Insulin and Body Weight Measurements That Are Inversely Associated with Subsequent Weight Regain 
PLoS ONE  2012;7(8):e42858.
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.
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.
LCD-induced changes in BMI, fasting insulin, and HOMA-IR are inversely associated with weight regain in the 6-month period following weight loss.
PMCID: PMC3414506  PMID: 22905179
11.  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.
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.
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.
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.
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; number, NCT00390637.)
PMCID: PMC3359496  PMID: 21105792
13.  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.
PMCID: PMC3257742  PMID: 22254101
starch; sugars; obesity; metabolic syndrome; insulin resistance; lipids; hormones; energy intake; energy expenditure; satiety
14.  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.
Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance.
To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study.
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.
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%.
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 NCT00390637
PMCID: PMC3038864  PMID: 21340022
15.  Dietary Protein and Blood Pressure: A Systematic Review 
PLoS ONE  2010;5(8):e12102.
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.
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.
PMCID: PMC2920332  PMID: 20711407
16.  Changes in skinfold thickness and waist circumference after 12 and 24 months resulting from the NHF-NRG In Balance-project 
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.
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).
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.
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.
PMCID: PMC2858095  PMID: 20370934
17.  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.
PMCID: PMC2453623  PMID: 18398140
18.  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.
PMCID: PMC2668625  PMID: 18224330
ATGL;  Skeletal muscle; Fiber type; Obesity; Protein

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