Dataset Information

Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial.

ABSTRACT: Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear.In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats.Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5-18.5%, p<0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p<0.05 for all), however, these associations did not remain after adjustment for visceral fat changes.Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk.ClinicalTrials.gov NCT01530724.

SUBMITTER: Gepner Y

PROVIDER: S-EPMC5708655 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial.

Gepner Yftach Y Shelef Ilan I Schwarzfuchs Dan D Cohen Noa N Bril Nitzan N Rein Michal M Tsaban Gal G Zelicha Hila H Yaskolka Meir Anat A Tene Lilac L Sarusy Benjamin B Rosen Philip P Hoffman Jay R JR Stout Jeffrey R JR Thiery Joachim J Ceglarek Uta U Stumvoll Michael M Blüher Matthias M Stampfer Meir J MJ Shai Iris I

PloS one 20171130 11

<h4>Background</h4>Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear.<h4>Methods</h4>In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participa ...[more]

PMID: 29190720

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Project description:Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.Sixteen overweight to obese adults (BMI 30.6?±?0.8; 67.2?±?4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n?=?8) or EX (n?=?8). Insulin sensitivity was determined using hyperinsulinaemic-euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry.Insulin sensitivity was improved with DIWL (20.6?±?4.7%) and EX (19.2?±?12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p?<?0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (-12.4?±?14.6%) and EX (-40.9?±?12.0%). Ceramide decreased with EX (-33.7?±?11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (-19.5?±?8.5%, p?<?0.05), but increased with EX (19.6?±?7.4%, p?<?0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions.Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis.ClinicalTrials.gov NCT00766298.

Project description:BACKGROUND/OBJECTIVES:Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. SUBJECTS/METHODS:This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. RESULTS:The mean IMCL level at 4.5 years was 0.481?±?0.279% of water resonance (mean?±?sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B?=?0.396 (0.069, 0.724); p?=?0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B?=?0.065 (0.001, 0.128); p?=?0.045) and conditional relative weight gain between ages 2 and 3 (B?=?0.052 (0.012, 0.093); p?=?0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B?=?0.028 (0.012, 0.044); p?=?0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. CONCLUSION:This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

Project description:BackgroundDNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (?mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets.ResultsAmong 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean?±?SD: 60.3?±?7.5 years) was higher than the chronological age (48.6?±?9.3 years) but strongly correlated (r?=?0.93; p?=?3.1?×?10-53). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p?<?0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (??=?0.23; p?=?0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r?=?0.94, p?=?1.5?×?10-55). mAging occurred, with no difference between lifestyle intervention groups (??=?0.9?±?1.9 years in MED/LC vs. ??=?1.3?±?1.9 years in LF; p?=?0.2); however, we observed a mAging attenuation in successful weight losers (>?5% weight loss) vs. weight-loss failures ( ??=?0.6 years vs. ??=?1.1 years; p?=?0.04), and in participants who completed the trial with healthy liver fat content (<?5% IHF) vs. participants with fatty liver (??=?0.6 years vs. ??=?1.8 years; p?=?0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p?<?0.05).ConclusionsLifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases.Trial registrationClinicalTrials.gov NCT01530724. Registered 10 February 2012, https://clinicaltrials.gov/ct2/show/study/NCT01530724 .

Project description:BACKGROUND:Self-monitoring of dietary intake is a valuable component of behavioral weight loss treatment; however, it declines quickly, thereby resulting in suboptimal treatment outcomes. OBJECTIVE:This study aimed to examine a novel behavioral weight loss intervention that aims to attenuate the decline in dietary self-monitoring engagement. METHODS:GoalTracker was an automated randomized controlled trial. Participants were adults with overweight or obesity (n=105; aged 21-65 years; body mass index, BMI, 25-45 kg/m2) and were randomized to a 12-week stand-alone weight loss intervention using the MyFitnessPal smartphone app for daily self-monitoring of either (1) both weight and diet, with weekly lessons, action plans, and feedback (Simultaneous); (2) weight through week 4, then added diet, with the same behavioral components (Sequential); or (3) only diet (App-Only). All groups received a goal to lose 5% of initial weight by 12 weeks, a tailored calorie goal, and automated in-app reminders. Participants were recruited via online and offline methods. Weight was collected in-person at baseline, 1 month, and 3 months using calibrated scales and via self-report at 6 months. We retrieved objective self-monitoring engagement data from MyFitnessPal using an application programming interface. Engagement was defined as the number of days per week in which tracking occurred, with diet entries counted if ?800 kcal per day. Other assessment data were collected in-person via online self-report questionnaires. RESULTS:At baseline, participants (84/100 female) had a mean age (SD) of 42.7 (11.7) years and a BMI of 31.9 (SD 4.5) kg/m2. One-third (33/100) were from racial or ethnic minority groups. During the trial, 5 participants became ineligible. Of the remaining 100 participants, 84% (84/100) and 76% (76/100) completed the 1-month and 3-month visits, respectively. In intent-to-treat analyses, there was no difference in weight change at 3 months between the Sequential arm (mean -2.7 kg, 95% CI -3.9 to -1.5) and either the App-Only arm (-2.4 kg, -3.7 to -1.2; P=.78) or the Simultaneous arm (-2.8 kg, -4.0 to -1.5; P=.72). The median number of days of self-monitoring diet per week was 1.9 (interquartile range [IQR] 0.3-5.5) in Sequential (once began), 5.3 (IQR 1.8-6.7) in Simultaneous, and 2.9 (IQR 1.2-5.2) in App-Only. Weight was tracked 4.8 (IQR 1.9-6.3) days per week in Sequential and 5.1 (IQR 1.8-6.3) days per week in Simultaneous. Engagement in neither diet nor weight tracking differed between arms. CONCLUSIONS:Regardless of the order in which diet is tracked, using tailored goals and a commercial mobile app can produce clinically significant weight loss. Stand-alone digital health treatments may be a viable option for those looking for a lower intensity approach. TRIAL REGISTRATION:ClinicalTrials.gov NCT03254953; https://clinicaltrials.gov/ct2/show/NCT03254953 (Archived by WebCite at http://www.webcitation.org/72PyQrFjn).

Project description:ImportanceModest weight loss can lead to meaningful risk reduction in adults with obesity. Although both behavioral economic incentives and environmental change strategies have shown promise for initial weight loss, to date they have not been combined, or compared, in a randomized clinical trial.ObjectiveTo test the relative effectiveness of financial incentives and environmental strategies, alone and in combination, on initial weight loss and maintenance of weight loss in adults with obesity.Design, setting, and participantsThis randomized clinical trial was conducted from 2015 to 2019 at 3 large employers in Philadelphia, Pennsylvania. A 2-by-2 factorial design was used to compare the effects of lottery-based financial incentives, environmental strategies, and their combination vs usual care on weight loss and maintenance. Interventions were delivered via website, text messages, and social media. Participants included adult employees with a body mass index (BMI; weight in kilograms divided by height in meters squared) of 30 to 55 and at least 1 other cardiovascular risk factor. Data analysis was performed from June to July 2021.InterventionsInterventions included lottery-based financial incentives based on meeting weight loss goals, environmental change strategies tailored for individuals and delivered by text messages and social media, and combined incentives and environmental strategies.Main outcome and measuresThe primary outcome was weight change from baseline to 18 months, measured in person.ResultsA total of 344 participants were enrolled, with 86 participants each randomized to the financial incentives group, environmental strategies group, combined financial incentives and environmental strategies group, and usual care (control) group. Participants had a mean (SD) age of 45.6 (10.5) years and a mean (SD) BMI of 36.5 (7.1); 247 participants (71.8%) were women, 172 (50.0%) were Black, and 138 (40.1%) were White. At the primary end point of 18 months, participants in the incentives group lost a mean of 5.4 lb (95% CI, -11.3 to 0.5 lb [mean, 2.45 kg; 95% CI, -5.09 to 0.23 kg]), those in the environmental strategies group lost a mean of a 2.2 lb (95% CI, -7.7 to 3.3 lb [mean, 1.00 kg; 95% CI, -3.47 to 1.49 kg]), and the combination group lost a mean of 2.4 lb (95% CI, -8.2 to 3.3 lb [mean, 1.09 kg; 95% CI, -3.69 to 1.49 kg]) more than participants in the usual care group. Financial incentives, environmental change strategies, and their combination were not significantly more effective than usual care. At 24 months, after 6 months without an intervention, the difference in the change from baseline was similar to the 18-month results, with no significant differences among groups.Conclusions and relevanceIn this randomized clinical trial, across all study groups, participants lost a modest amount of weight but those who received financial incentives, environmental change, or the combined intervention did not lose significantly more weight than those in the usual care group. Employees with obesity may benefit from more intensive individualized weight loss strategies.Trial registrationClinicalTrials.gov Identifier: NCT02878343.

Project description:BackgroundOne of the major challenges in obesity treatment is to explain the high variability in the individual's response to specific dietary and physical activity interventions. With this study, we tested the hypothesis that specific DNA methylation changes reflect individual responsiveness to lifestyle intervention and may serve as epigenetic predictors for a successful weight-loss.MethodsWe conducted an explorative genome-wide DNA methylation analysis in blood samples from 120 subjects (90% men, mean ± SD age = 49 ± 9 years, body mass-index (BMI) = 30.2 ± 3.3 kg/m2) from the 18-month CENTRAL randomized controlled trial who underwent either Mediterranean/low-carbohydrate or low-fat diet with or without physical activity.ResultsAnalyses comparing male subjects with the most prominent body weight-loss (responders, mean weight change - 16%) vs. non-responders (+ 2.4%) (N = 10 each) revealed significant variation in DNA methylation of several genes including LRRC27, CRISP2, and SLFN12 (all adj. P < 1 × 10-5). Gene ontology analysis indicated that biological processes such as cell adhesion and molecular functions such as calcium ion binding could have an important role in determining the success of interventional therapies in obesity. Epigenome-wide association for relative weight-loss (%) identified 15 CpGs being negatively correlated with weight change after intervention (all combined P < 1 × 10- 4) including new and also known obesity candidates such as NUDT3 and NCOR2. A baseline DNA methylation score better predicted successful weight-loss [area under the curve (AUC) receiver operating characteristic (ROC) = 0.95-1.0] than predictors such as age and BMI (AUC ROC = 0.56).ConclusionsBody weight-loss following 18-month lifestyle intervention is associated with specific methylation signatures. Moreover, methylation differences in the identified genes could serve as prognostic biomarkers to predict a successful weight-loss therapy and thus contribute to advances in patient-tailored obesity treatment.

Dataset Information

Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial.

Publications

Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial.

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