Dietary Weight Loss Intervention Research Articles

Exploring experiences of people with knee osteoarthritis who received a physiotherapist-delivered dietary weight loss and exercise intervention: a mixed methods study.

Explore the experiences of people with knee osteoarthritis who received a very low energy diet (VLED) and exercise program from a physiotherapist. Mixed methods study involving questionnaires (n=42) and semi-structured interviews (n=22) with randomized control trial participants with knee osteoarthritis who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction, and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analysed based on the principles of reflexive thematic analysis. Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). Four themes were developed from the interviews: 1) one-stop-shop of exercise and diet; 2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); 3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); 4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). This study provides, to our knowledge, the first documented perspectives from people with osteoarthritis who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolised dietary intervention for some people with knee osteoarthritis with overweight and obesity.

Abstract 2189: Tirzepatide mitigates obesity-associated metabolic dysregulation and tumor progression in a mouse model of triple-negative breast cancer

Abstract Obesity is an established risk factor for breast cancer. Dietary and surgical weight loss interventions reduce breast cancer risk but have significant limitations to their widespread use as anticancer strategies. Incretin-based pharmaceuticals safely and effectively promote weight loss, but whether these drugs exert similar protective effects against cancer is unknown. Here we test whether weight loss induced by the glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide limits tumor growth in an orthotopic mouse model of triple-negative breast cancer. Ten-week-old female C57BL/6NCrl mice were randomized to either a 10 kcal% low-fat diet (control; n=14) or 60 kcal% high-fat diet to promote diet-induced obesity (DIO; n=43). After 18 weeks on diet, DIO mice were randomized by body weight to either i) remain on the high-fat diet (DIO; n=15); ii) lose weight with tirzepatide (TZP; n=13); or iii) lose weight with 30% daily calorie restriction relative to control mice (CR; n=15). All mice were subcutaneously injected with either TZP or vehicle every other day for 13 weeks with the following escalating dosing schedule: 3 nmol/kg TZP in week 1; 10 nmol/kg TZP in weeks 2-3; 20 nmol/kg TZP in weeks 4-7; 30 nmol/kg TZP in weeks 8-11; and 40 nmol/kg TZP in weeks 12-13. Fasting blood glucose and body composition was assessed after 9 weeks of weight loss, and 35,000 E0771 cells were orthotopically transplanted into the 4th mammary fat pad. Tumors growth was monitored for 4 weeks. TZP-treated mice lost on average >20% weight loss by week 4 and remained at or below 20% weight loss for the remainder of the study. Directly prior to E0771 tumor cell injections, TZP-treated mice had lost 23.6±8.9% body weight, versus 39.7±3.6% in CR mice. Relative to DIO mice, blood glucose control was restored in both weight loss groups (DIO: 149.5±18.5 mg/dl; TZP: 124.5±15.5 mg/dl; CR: 107.6±18.8 mg/dl) and >87.5% of the lost weight was attributed to fat mass, rather than lean mass, for TZP-treated and CR mice. Notably, tirzepatide suppressed tumor growth relative to DIO, but the CR group had a greater anticancer effect than TZP. Reduced tumor mass in both weight loss groups was accompanied by a significant reduction in circulating IGF-1, insulin, and leptin relative to DIO mice. These findings are timely and important because i) obesity is a highly prevalent metabolic disease that increases risk and progression of breast cancer and >13 other cancers; ii) incretin therapies, which show promise as highly effective weight loss drugs, are increasingly being prescribed; and iii) the tumor suppressive effects of tirzepatide described herein newly suggest incretin agonism as another propitious option for breaking the obesity-cancer link. Citation Format: Elaine M. Glenny, Alyssa N. Ho, Violet A. Kiesel, Fangxin Chen, Claire E. Gates, Evan M. Paules, Ruihan Xu, C. Alex Holt, Michael F. Coleman, Stephen D. Hursting. Tirzepatide mitigates obesity-associated metabolic dysregulation and tumor progression in a mouse model of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2189.

Abstract P348: Weight Loss of Machine Learning Identified Metabolic Subtypes in Response to Dietary Interventions

Introduction: Metabolic syndrome is a constellation of metabolic risk factors. However, various combinations of metabolic disorders may exhibit distinct responses to weight loss interventions. Objective: To identify metabolic subtypes using the machine learning method and assess their associations with weight loss response to dietary interventions. Methods: The study includes 645 participants from the POUNDS Lost trial. Five criteria for metabolic syndrome were used as the grouping factors. Hierarchical clustering was performed with an 8:2 train/test ratio. Results: Three metabolic subtypes were identified and validated among the POUNDS Lost participants. Cluster 1 was characterized by high proportions of central obesity and high blood pressure but low triglycerides; Cluster 2 showed central obesity with relatively low blood pressure; Cluster 3 had the lowest level of central obesity and blood pressure but the highest triglycerides level. Changes in body weight varied significantly across clusters (p=0.003 at 6 months and p< 0.001 at 2 years). At 6 months, adjusted least-square mean (SE) weights were: -6.5 (0.8) kg in cluster 1, -5.4 (0.6) kg in cluster 2, and -4.2 (0.7) kg in cluster 3. Participants regained weight after 6 months, but the difference across the clusters persisted: -5.5 (1.0) kg in Cluster 1, -3.1 (0.8) kg in Cluster 2, and -1.7 (0.8) kg in Cluster 3. Conclusion: We identified 3 metabolic subtypes that predict different responses to dietary weight loss interventions, which may contribute to subtype-specific precision medicine for obesity prevention and management.

Changes in bile acid subtypes and improvements in lipid metabolism and atherosclerotic cardiovascular disease risk: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial

BackgroundDistinct circulating bile acid (BA) subtypes may play roles in regulating lipid homeostasis and atherosclerosis. ObjectivesWe investigated whether changes in circulating BA subtypes induced by weight-loss dietary interventions were associated with improved lipid profiles and atherosclerotic cardiovascular disease (ASCVD) risk estimates. MethodsThis study included adults with overweight or obesity (n = 536) who participated in a randomized weight-loss dietary intervention trial. Circulating primary and secondary unconjugated BAs and their taurine-/glycine-conjugates were measured at baseline and 6 mo after the weight-loss diet intervention. The ASCVD risk estimates were calculated using the validated equations. ResultsAt baseline, higher concentrations of specific BA subtypes were related to higher concentrations of atherogenic very low-density lipoprotein lipid subtypes and ASCVD risk estimates. Weight-loss diet-induced decreases in primary BAs were related to larger reductions in triglycerides and total cholesterol [every 1 standard deviation (SD) decrease of glycocholate, glycochenodeoxycholate, or taurochenodeoxycholate was related to β (standard error) –3.3 (1.3), –3.4 (1.3), or –3.8 (1.3) mg/dL, respectively; PFDR < 0.05 for all]. Greater decreases in specific secondary BA subtypes were also associated with improved lipid metabolism at 6 mo; there was β –4.0 (1.1) mg/dL per 1-SD decrease of glycoursodeoxycholate (PFDR =0.003) for changes in low-density lipoprotein cholesterol. We found significant interactions (P-interaction < 0.05) between dietary fat intake and changes in BA subtypes on changes in ASCVD risk estimates; decreases in primary and secondary BAs (such as conjugated cholate or deoxycholate) were significantly associated with improved ASCVD risk after consuming a high-fat diet, but not after consuming a low-fat diet. ConclusionsDecreases in distinct BA subtypes were associated with improved lipid profiles and ASCVD risk estimates, highlighting the importance of changes in circulating BA subtypes as significant factors linked to improved lipid metabolism and ASCVD risk estimates in response to weight-loss dietary interventions. Habitual dietary fat intake may modify the associations of changes in BAs with ASCVD risk.This trial was registered at clinicaltrials.gov as NCT00072995

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

The effects of a dietary intervention for weight loss and gene-diet interactions on body composition in adults

The effects of a dietary intervention for weight loss and gene-diet interactions on body composition in adults

Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.

Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats. Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes. By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group). Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms.

DNA Methylation at ABCG1 and Long-term Changes in Adiposity and Fat Distribution in Response to Dietary Interventions: The POUNDS Lost Trial.

To examine whether participants with different levels of diabetes-related DNA methylation at ABCG1 might respond differently to dietary weight loss interventions with long-term changes in adiposity and body fat distribution. The current study included overweight/obese participants from the POUNDS Lost trial. Blood levels of regional DNA methylation at ABCG1 were profiled by high-resolution methylC-capture sequencing at baseline among 673 participants, of whom 598 were followed up at 6 months and 543 at 2 years. Two-year changes in adiposity and computed tomography-measured body fat distribution were calculated. Regional DNA methylation at ABCG1 showed significantly different associations with long-term changes in body weight and waist circumference at 6 months and 2 years in dietary interventions varying in protein intake (interaction P < 0.05 for all). Among participants assigned to an average-protein (15%) diet, lower baseline regional DNA methylation at ABCG1 was associated with greater reductions in body weight and waist circumference at 6 months and 2 years, whereas opposite associations were found among those assigned to a high-protein (25%) diet. Similar interaction patterns were also observed for body fat distribution, including visceral adipose tissue, subcutaneous adipose tissue, deep subcutaneous adipose tissue, and total adipose tissue at 6 months and 2 years (interaction P < 0.05 for all). Baseline DNA methylation at ABCG1 interacted with dietary protein intake on long-term decreases in adiposity and body fat distribution. Participants with lower methylation at ABCG1 benefitted more in long-term reductions in body weight, waist circumference, and body fat distribution when consuming an average-protein diet.

Evaluation of the "Shifting Weight using Intermittent Fasting in night-shift workers" weight loss interventions: a mixed-methods protocol.

Shift workers are at a greater risk for obesity-related conditions. The impacts of working at night presents a challenge for designing effective dietary weight-loss interventions for this population group. The Shifting Weight using Intermittent Fasting in night-shift workers (SWIFt) study is a world-first, randomized controlled trial that compares three weight-loss interventions. While the trial will evaluate the effectiveness of weight-loss outcomes, this mixed-methods evaluation aims to explore for who weight-loss outcomes are achieved and what factors (intervention features, individual, social, organisational and wider environmental) contribute to this. A convergent, mixed-methods evaluation design was chosen where quantitative and qualitative data collection occurs concurrently, analyzed separately, and converged in a final synthesis. Quantitative measures include participant engagement assessed via: dietary consult attendance, fulfillment of dietary goals, dietary energy intake, adherence to self-monitoring, and rates for participant drop-out; analyzed for frequency and proportions. Regression models will determine associations between engagement measures, participant characteristics (sex, age, ethnicity, occupation, shift type, night-shifts per week, years in night shift), intervention group, and weight change. Qualitative measures include semi-structured interviews with participants at baseline, 24-weeks, and 18-months, and fortnightly audio-diaries during the 24-week intervention. Interviews/diaries will be transcribed verbatim and analyzed using five-step thematic framework analysis in NVivo. Results from the quantitative and qualitative data will be integrated via table and narrative form to interrogate the validity of conclusions. The SWIFt study is a world-first trial that compares the effectiveness of three weight-loss interventions for night shift workers. This mixed-methods evaluation aims to further explore the effectiveness of the interventions. The evaluation will determine for who the SWIFt interventions work best for, what intervention features are important, and what external factors need to be addressed to strengthen an approach. The findings will be useful for tailoring future scalability of dietary weight-loss interventions for night-shift workers.Clinical trial registration: This evaluation is based on the SWIFt trial registered with the Australian New Zealand Clinical Trials Registry [ACTRN 12619001035112].

1257-P: Changes in Circulating Pancreatic Islet-Specific MicroRNA-375 Levels and Improvements in Insulin Sensitivity and Glucose Metabolism in Response to Weight-Loss Diets with Different Compositions of Macronutrients—The POUNDS Lost Trial

Pancreatic islet-specific microRNA-375 (miR-375) regulates insulin secretion and has an essential role in β-cell compensation when escalating insulin demand. We recently reported that changes in circulating miR-375 were associated with improved diabetogenic fat depots. Here, we investigated whether changes in circulating miR-375 induced by weight-loss diet interventions with different macronutrient intakes (fat, carbohydrate (carb), and protein) were related to improved insulin sensitivity and glucose metabolism. This study included participants from the POUNDS Lost trial with available data on circulating miR-375-3p at baseline (n=520) and its changes from baseline to 6 months after weight-loss diet interventions (n=508). At baseline, higher levels of miR-375 were related to lower degrees of BMI, total adipose tissue mass, and whole-body fat content (P &amp;lt;0.05 for all). There was a significant increase in miR-375 levels from baseline to 6 months (P by paired t-test &amp;lt;0.001). We found that associations of changes in miR-375 with changes in fasting insulin, glucose, and insulin resistance (HOMA-IR) were significantly modified by carb and fat intakes (P interaction &amp;lt;0.05 for all). In response to a low-fat and high-carb diet, a greater increase in miR-375 was significantly associated with larger reductions of fasting insulin and HOMA-IR at 6 months, regardless of baseline miR-375 levels. On the other hand, in response to a high-fat and low-carb diet intervention, there were significant positive associations between miR-375 changes and changes in glucose, insulin, and HOMA-IR. These results suggest that changes in the pancreatic islet-specific miRNA expression are associated with weight-loss diet intervention outcomes on insulin sensitivity and glucose metabolism. Different macronutrient intakes may modify these associations. Disclosure Y.Heianza: None. Q.Xue: None. H.Ma: None. G.Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F.Sacks: None. L.Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679)

48-LB: Changes in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Changes of Insulin Sensitivity in Response to Weight-Loss Diets—The POUNDS Lost trial

Evidence on the benefits of non-nutritive sweeteners for weight management and improving insulin sensitivity and glucose metabolism is inconsistent. Recently, high levels of circulating erythritol, a sugar alcohol used as one of the non-nutritive sweeteners, have been linked to increased risks of type 2 diabetes and its vascular complications. Whether changes in circulating erythritol levels are related to insulin sensitivity and glucose metabolism remains unknown. Here, we investigated whether changes in plasma erythritol induced by weight-loss diet interventions were related to improved insulin sensitivity and glucose metabolism. This study included overweight or obese participants without diabetes or unstable cardiovascular disease from the POUNDS Lost trial with available data on circulating erythritol at baseline (n=805) and its changes from baseline to 6 months (n=670) and 2 years (n=533) during weight-loss diet interventions. At baseline, higher plasma levels of erythritol were related to hyperinsulinemia and greater degrees of insulin resistance assessed by HOMA-IR, even after adjusting for covariates, including BMI (P &amp;lt;0.05 for all). In response to weight-loss dietary interventions, a greater decrease in plasma erythritol was significantly associated with larger reductions of fasting insulin (p= 0.0001) and HOMA-IR (p=0.039) at 6 months, regardless of the initial levels of BMI, erythritol, and the respective outcome. Similarly, we found a significant association between long-term changes in erythritol and a 2-year reduction of fasting insulin (p=0.0027). In conclusion, circulating plasma erythritol, a marker of non-nutritive sweetener consumption, was significantly associated with hyperinsulinemia and insulin sensitivity among adults with overweight or obesity. Weight-loss diet-induced decreases in plasma erythritol were related to improved insulin sensitivity. Disclosure Y. Heianza: None. Q. Xue: None. J. Rood: None. G. Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F. Sacks: None. L. Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679, 2P20GM109036-06A1-7233)

Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs

IntroductionClara cell 16-kDa protein (CC16) is an anti-inflammatory, immunomodulatory secreted pulmonary protein with reduced serum concentrations in obesity according to recent data. ObjectiveStudies focused solely on bodyweight, which does not properly reflect obesity-associated implications of the metabolic and reno-cardio-vascular system. The purpose of this study was therefore to examine CC16 in a broad physiological context considering cardio-metabolic comorbidities of primary pulmonary diseases. MethodsCC16 was quantified in serum samples in a subset of the FoCus (N = 497) and two weight loss intervention cohorts (N = 99) using ELISA. Correlation and general linear regression analyses were applied to assess CC16 effects of lifestyle, gut microbiota, disease occurrence and treatment strategies. Importance and intercorrelation of determinants were validated using random forest algorithms. ResultsCC16 A38G gene mutation, smoking and low microbial diversity significantly decreased CC16. Pre-menopausal female displayed lower CC16 compared to post-menopausal female and male participants. Biological age and uricosuric medications increased CC16 (all p < 0.01). Adjusted linear regression revealed CC16 lowering effects of high waist-to-hip ratio (est. −11.19 [−19.4; −2.97], p = 7.99 × 10−3), severe obesity (est. −2.58 [−4.33; −0.82], p = 4.14 × 10−3) and hypertension (est. −4.31 [−7.5; −1.12], p = 8.48 × 10−3). ACEi/ARB medication (p = 2.5 × 10−2) and chronic heart failure (est. 4.69 [1.37; 8.02], p = 5.91 × 10−3) presented increasing effects on CC16. Mild associations of CC16 were observed with blood pressure, HOMA-IR and NT-proBNP, but not manifest hyperlipidemia, type 2 diabetes, diet quality and dietary weight loss intervention. ConclusionA role of metabolic and cardiovascular abnormalities in the regulation of CC16 and its modifiability by behavioral and pharmacological interventions is indicated. Alterations by ACEi/ARB and uricosurics could point towards regulatory axes comprising the renin-angiotensin-aldosterone system and purine metabolism. Findings altogether strengthen the importance of interactions among metabolism, heart and lungs.

0001 Effect of Time-Restricted Eating on Actigraphy-Derived Sleep Parameters

Abstract Introduction Time-restricted eating (TRE) is an emerging dietary intervention for weight loss. Sleep can be influenced by timing of food intake. Nevertheless, the impact of TRE on sleep patterns remains under-explored. The Time-Restricted Intake of Meals (TRIM) study was a parallel-arm, controlled feeding trial in 41 adults with obesity and prediabetes or untreated diabetes, randomized to TRE (8am-6pm) or usual eating pattern (UEP; 8am-12am) for 12 weeks, where the primary outcome was weight change. We hypothesized that TRE would cause changes in sleep/wake patterns. Methods This was a post-hoc analysis of TRIM using wrist actigraphy data obtained at baseline and week-12. We applied an objective process to determine sleep parameters after sleep estimation (Cole-Kripke) from actigraphy data. We analyzed 6 days/nights of recordings for each participant at each timepoint. Outcomes were sleep duration defined by mean total sleep time per 24-hour period (TST), sleep timing measured by mid-sleep time, sleep onset/offset, and sleep continuity. We used paired t-tests or Wilcoxon signed rank tests to compare data between baseline and week-12 within intervention arms and Mann-Whitney U tests or Wilcoxon signed rank tests to compare changes between intervention arms. Results 38 participants (20 UEP; 18 TRE) with adequate actigraphy data (mean age 60 years, 92% female, and 92% Black) were analyzed. Baseline TST (mean□SD) was 394□90 minutes and 386□81 minutes for UEP and TRE, respectively. Week-12 TST was 397□92 minutes and 444□95 minutes for UEP and TRE, respectively. Compared to UEP, TRE increased TST by 55 minutes (p=0.03). TRE shifted mid-sleep time to 44 minutes earlier, from 3:24am to 2:40am (p=0.01), while UEP maintained the same mid-sleep time at 3:15am. Sleep onset shifted from a median of 12:22am to 11:52pm in TRE (p=0.03) while it remained stable in UEP (p=0.97). There were no differences in sleep offset and sleep continuity within and between intervention arms. Conclusion Sleep behaviors were different by treatment arm with increased total sleep time and earlier sleep onset in TRE participants. TRE may have ancillary consequences on sleep, which could have clinical implications for sleep regulation. Support (if any) AHA SFRN 17SFRN33590069 K23DK133690

The administration of Exendin-4 and CCK affects food intake differentially in female and male rats tested on an alternate day fasting paradigm

Alternate day fasting (ADF) which involves the repetition of a 2-day cycle of a day of free access to food followed by a day of limited or no access to food, is an effective dietary intervention for weight loss in both humans and rats. We have previously reported that when presented with a high energy (HE) and standard chow diet, rats maintained on an ADF schedule displayed decreased HE diet preference compared to controls. Both male and female ADF rats increased overall intake of chow. However, this increase was driven by both meal size and meal number for males and only number of meals for females. Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. It appears that CCK decreases food intake primarily through satiety signals whereas GLP-1 signaling may reduce intake by satiety and reward cues. Here, female and male rats were administered (i.p.) saline, 3.0 µg/kg Ex-4 (3 h before test), 3.0 µg/kg CCK (15 min before test) or a combination of both. Next, all rats were presented 23-h access to both HE diet and chow following food-restriction (ADF) or free access to chow (CON). Compared to saline-control sessions, administration of the combination of Ex-4 and CCK, but not Ex-4 or CCK alone, resulted in a decrease in both HE and chow intake early in the session for male ADF rats but the combination primarily decreased chow diet intake early in the session for female ADF rats. Thus, it appears that under these energy homeostatic conditions, administration of Ex-4 or CCK alone does not affect intake in ADF rats, but the combination produces decreases in feeding that are more than the sum of their individual effects. These findings support a role for the combination of GLP-1 and CCK signaling in the changes in diet preference induced by an alternate day fasting paradigm differentially in female and male rats.

Cognitive-behavioral and dietary weight loss intervention in adult kidney transplant recipients with overweight and obesity: Results of a pilot RCT study (Adi-KTx).

The obesity epidemic and its health consequences have not spared the population of kidney transplant (KTx) candidates and recipients. In addition, KTx recipients are susceptible to weight gain after transplantation. Overweight and obesity after KTx are strongly associated with adverse outcomes. Therefore, we designed a randomized controlled, mono-center study to specifically test the effectiveness of a primarily cognitive-behavioral approach supplemented by nutritional counseling for weight reduction following KTx as the intervention group (IG) in comparison to a brief self-guided intervention as control group (CG). The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00017226). Fifty-six KTx patients with a BMI from 27 to 40 kg/m2 were included in this study and randomized to the IG or CG. Main outcome was the number of participants achieving a 5% weight loss during the treatment phase. Additionally, participants were assessed 6 and 12 months after the end of the 6-month treatment phase. Participants significantly lost weight without group differences. 32.0% (n = 8) of the patients in the IG and 16.7% (n = 4) of the patients in the CG achieved a weight loss of 5% or more. Weight loss was largely maintained during follow-up. Retention and acceptance rate in the IG was high, with 25 (out of 28) patients completing all 12 sessions and one patient completing 11 sessions. Short-term, cognitive-behaviorally oriented weight loss treatment seems to be feasible and acceptable for patients after KTx who suffer from overweight or obesity. This clinical trial was ongoing at the onset of the COVID-19 pandemic which might have influenced study conduct and results. Clinical Trial Registration: https://clinicaltrials.gov/ DRKS-ID: DRKS00017226.

Sustainable dietary weight loss intervention and its effects on cardiometabolic parameters and greenhouse gas emissions: study protocol of a randomised controlled trial with overweight and obese adults in Ouagadougou, Burkina Faso

IntroductionThe global obesity epidemic and its adverse health effects have reached sub-Saharan Africa. In some urban settings, like Burkina Faso’s capital Ouagadougou, up to 43% of the adult population are...

A285 CHANGE IN ALT DURING MODIFIED OPTIFAST WEIGHT LOSS PROGRAM IN INDIVIDUALS AT RISK FOR NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract Background Obesity is linked to various health complications, including diabetes, metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent cause of abnormally high alanine aminotransferase (ALT) levels. ALT is released at higher levels during hepatocellular injury and represents a simple, low cost and non-invasive method of assessing liver damage. There are conflicting data on ALT response to weight loss between men and women, with some evidence of transient increase in ALT levels in women. Purpose The aim of this study was to assess the impact of a dietary weight loss intervention with Optifast on ALT in patients with obesity who have baseline elevated ALT levels. Method This was a retrospective cohort study of Ontario adults who participated in a 26 week weight loss program, including 6 or 12 weeks of low-calorie liquid diet meal replacement with Optifast 900® (Nestlé, Canada), between 1992 and 2015. We included patients with elevated baseline ALT levels, defined by &amp;gt; 40 U/L, who had at least one follow-up ALT between week 15 and 26. We excluded patients with nonadherence to dietary intervention, established liver disease or using hepatotoxic drugs, excessive alcohol intake (&amp;gt;11U/wk for females and &amp;gt;14U/wk for males), and insufficient data to calculate FIB-4. The primary outcome was change in ALT levels, measured by normalization (post-intervention ALT &amp;lt; 40 U/L), percentage decrease and absolute decrease. Multiple linear regressions were obtained for the relationship between ALT changes and age, sex, body mass index (BMI) and FIB-4. All analyses were conducted in SPSS. P value of ≤0.05 was considered statistically significant. Result(s) 444 patients met study criteria. Mean age was 47.1 years +/- 10.9, 49 % of patients were female, and mean BMI was 43.5 kg/m2 +/- 7.9. All patients lost weight, with mean weight loss 27.3 kg +/- 11.5 and a mean 20.7% decrease from baseline weight. Mean ALT at baseline was 58.9 U/L +/- 25.4 and mean ALT post intervention was 32.3 U/L +/- 28.1 (p &amp;lt;0.01). 85.1% of patients had normalization of ALT. Mean % decrease in ALT was 41.9% and mean absolute decrease in ALT was 26.6 U/L +/- 25.4. Younger age and higher baseline FIB-4 were significantly associated with a larger decrease in ALT levels, while sex and initial BMI were not significantly associated with changes in ALT. Conclusion(s) In patients with obesity and baseline elevated ALT, dietary weight loss intervention with Optifast leads to ALT normalization in most patients, regardless of sex. Younger age at baseline and higher baseline FIB-4 are significantly associated with greater decrease in ALT. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Abstract P338: Circulating microRNA-19 and Cardiovascular Risk Reduction in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial

Introduction: MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention. Methods: This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months. Results: Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P trend &lt;0.05). There were significant interactions between changes in miR-19a/b-3p and sleep disturbance for changes in ASCVD risk (P interaction&lt;0.005). Participants with greater decreases in miR-19a/b-3p with no/slight amount of sleep disturbance had a greater reduction of ASCVD risk from baseline to 6 months than those with moderate/great amount of sleep disturbance. In addition, changes in physical activity modified the associations between changes in miR-19a-3p and ASCVD risk. A greater decrease in miR-19a-3p was significantly associated with a greater reduction in ASCVD among participants with an increase in physical activity from baseline to 6 months. These positive associations were reversed and not significant among participants with no change/decrease in physical activity and moderate/great amount of sleep disturbance. Conclusions: In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.

Abstract 56: DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressures in Response to Weight-Loss Diets

Introduction: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. Hypothesis: DNAm levels of genes related to both birthweight and blood pressure were associated with changes in blood pressures in response to dietary weight-loss interventions. Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm levels as the average methylation level within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793). Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. Results: We found that the regional DNAm at LINC00319, but not the other genes, showed different associations with 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among participants assigned low- or high-fat diets (P for interaction &lt; 0.05 for all, Figure ). In response to low-fat diet, per standard deviation higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in SBP (β: -1.481; standard error [SE]: 0.632; P = 0.020) and DBP (β: -1.096; SE: 0.413; P = 0.009). Three trajectories of changes in SBP and DBP were identified, and participants with higher baseline regional DNAm at LINC00319 were less likely to have stable or increased blood pressure levels. Conclusions: Our findings indicate that higher regional DNAm level at LINC00319 was significantly associated with greater long-term reduction in blood pressure in response to a low-fat diet, suggesting people with higher regional DNAm levels benefited more from eating a low-fat weight-loss diet.

Abstract P619: DNA Methylation at SREBF1 and Long-Term Changes in Body Composition: The POUNDS Lost Trial

Introduction: A previous epigenome-wide association study has causally linked DNA methylation (DNAm) at the SREBF1 gene (cg11024682) with obesity and lipids. However, little is known about whether DNAm at SREBF1 is associated with long-term changes in body adiposity and composition. Hypothesis: We hypothesized that participants with different DNAm at SRBF1 might respond differently to dietary weight-loss interventions on changes in body adiposity and composition. Methods: The current study included 314 individuals with overweight or obese, who participated in POUNDS Lost: a 2-year randomized dietary weight-loss trial. The blood DNAm level was profiled by methylC-capture sequencing at baseline. Regional DNAm at SREBF1 was calculated as the average methylation level over CpGs within ±250 bp of cg11024682. Body composition, including total fat mass (FM), percentage of FM (FM%), total fat-free mass (FFM), percentage of FFM (FFM%), and percentage of trunk fat (TF%) were measured by dual-energy X-ray absorptiometry (DEXA) at baseline, 6 months, and 2 years. Results: Lower regional DNAm at SREBF1 was significantly associated with changes in body composition across 2 years ( Table ). At 6 months, per SD lower regional DNAm at SREBF1 was significantly associated with greater reductions in FM (β [SE] -0.23 [0.07], p=0.002), FM% (-0.30 [0.09], p&lt;0.001), and TF% (-0.44 [0.13], p&lt;0.001), and greater increases in FFM (0.18 [0.08], p=0.028) and FFM% (0.30 [0.09], p&lt;0.001), regardless of dietary intervention groups and independent of concurrent weight loss. Such association remained at 2 years: FM (β [SE] -0.21 [0.10], p=0.045), FM% (-0.32 [0.11], p=0.004), TF% (-0.36 [0.16], p=0.026), FFM (0.22 [0.12], p=0.07) and FFM% (0.32 [0.11], p=0.004). Conclusions: Overweight and obese individuals with a lower regional DNAm at SREBF1 achieved greater improvement in body composition across the 2-year intervention, independent of concurrent weight loss, suggesting DNAm at SREBF1 is predictive of individuals’ response to treatment.