Wilkinson MJ, Padilla E, Wang Y
… +13 more, Raygani S, Manoogian ENC, Laing K, Tong K, Liu L, Van D, Nguyen J, Saltiel AR, Reilly SM, O'Neal M, Panda S, Majithia AR, Taub PR
Obesity (Silver Spring)
· 2026 Jul · PMID 42229885
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OBJECTIVE: Examine time-restricted eating (TRE) as a strategy to promote weight loss and cardiometabolic health in adults with obesity. METHODS: TRE in obesity and ADipose Tissue (TREAD) was a single-center 12-week RCT,...OBJECTIVE: Examine time-restricted eating (TRE) as a strategy to promote weight loss and cardiometabolic health in adults with obesity. METHODS: TRE in obesity and ADipose Tissue (TREAD) was a single-center 12-week RCT, involving 1:1 randomization to 10-h TRE versus standard of care (SOC) in adults with obesity (BMI 30-50 kg/m) without diabetes and baseline eating window ≥ 14 h/day. The primary endpoint was change in weight (kg). Exploratory RNA-seq in subcutaneous abdominal adipose tissue was performed in a subgroup of participants. RESULTS: A total of 61 participants were randomized, and 52 (26 TRE, 26 SOC) completed the study. Mean ± SD age was 55 ± 12.1 years, n = 35 were (58%) women, n = 35 were non-Hispanic White (58%), and BMI was 35.5 ± 4.8 kg/m. With TRE, the mean total reduction in weight from baseline to end of study was -4.59 kg (95% CI -5.51, -3.67) (-4.6%) versus -1.68 kg (95% CI -2.59, -0.77) (-1.7%) with SOC (between-group difference -2.91 kg [-4.21, -1.60]) (p < 0.001), primarily through loss of body fat. Downregulation of proinflammatory genes was observed in adipose tissue during TRE. CONCLUSIONS: In adults with obesity, compared with SOC dietary counseling alone, TRE promotes weight loss, healthier body composition, and, in exploratory analyses, reduction in adipose tissue proinflammatory gene expression. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04916730.
OBJECTIVE: This study aimed to evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with risks of osteoporosis, major osteoporotic fractures, and degenerative musculoskeletal disorders in non...OBJECTIVE: This study aimed to evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with risks of osteoporosis, major osteoporotic fractures, and degenerative musculoskeletal disorders in nondiabetic adults with obesity compared with other obesity medications. METHODS: This retrospective cohort study included deidentified TriNetX data on ≥ 50-year-old nondiabetic adults with obesity. After 1:1 propensity score matching on demographic, clinical, and laboratory covariates, 18,062 GLP-1 RA users were compared with non-GLP-1 medication users. The primary outcome was incident osteoporosis; secondary outcomes included major osteoporotic fractures, cervical and thoracolumbar disc disorders, and osteoarthritis. RESULTS: GLP-1 RA use was associated with lower risks of osteoporosis (relative risk [RR] 0.48; 95% CI, 0.43-0.52; number needed to treat [NNT] = 28), major osteoporotic fractures (RR 0.15; 95% CI, 0.11-0.22; NNT = 88), cervical disc degeneration (RR 0.34; 95% CI, 0.28-0.41; NNT = 63), thoracolumbar disc disease (RR 0.36; 95% CI, 0.33-0.40; NNT = 20), and osteoarthritis (RR 0.45; 95% CI, 0.43-0.48; NNT = 9). Protective associations were consistent across age, sex, BMI, and drug subtype subgroups and remained robust in sensitivity analyses. CONCLUSIONS: GLP-1 RA use was associated with favorable musculoskeletal outcomes, including lower risks of osteoporosis and fractures, in nondiabetic adults with obesity compared with other obesity medications.
OBJECTIVE: Food addiction (FA) is implicated in obesity, yet the potential moderating role of mindful eating and the underlying neural mechanisms in youth remain unclear. METHODS: This study integrated a multicenter cros...OBJECTIVE: Food addiction (FA) is implicated in obesity, yet the potential moderating role of mindful eating and the underlying neural mechanisms in youth remain unclear. METHODS: This study integrated a multicenter cross-sectional survey, a longitudinal study with 6- and 12-month follow-ups, and an independent magnetic resonance imaging (MRI) sample. FA, eating motives, mindful eating, BMI z-score, fat content, and visceral fat level were assessed. Analyses utilized structural equation modeling, latent growth modeling, and voxel-based morphometry. RESULTS: Among 2071 screened, 1601 youth (55.5% boys; mean age = 12.69 ± 3.04 years) completed the baseline survey, with 880 and 564 completing the 6- and 12-month follow-ups, respectively. FA mediated the relationship between eating motives and weight status, and mindful eating moderated this pathway (p < 0.05). Longitudinally, baseline FA predicted accelerated accumulation of fat content and visceral fat level, but not BMI z-score (p > 0.05). The independent 75-MRI sample revealed that left insula gray-matter volume was negatively associated with FA but positively associated with mindful eating. CONCLUSIONS: FA may link eating motives to fat accumulation in youth, particularly abdominal fat; mindful eating may be protective, with left insula structure and left insula-striatum connectivity as possible neural correlates.
Vales-Villamarín C, Berthold A, Lacher M
… +2 more, Körner A, Landgraf K
Obesity (Silver Spring)
· 2026 Jul · PMID 42206925
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OBJECTIVE: The lipid droplet-associated hydrolase (LDAH) is a lipid droplet-associated protein with an uncharacterized role in human adipose tissue (AT) and obesity; we aimed to investigate its role in human AT and its r...OBJECTIVE: The lipid droplet-associated hydrolase (LDAH) is a lipid droplet-associated protein with an uncharacterized role in human adipose tissue (AT) and obesity; we aimed to investigate its role in human AT and its relevance for childhood obesity. METHODS: LDAH variant rs13385191 and gene expression were analyzed in a cross-sectional study of subcutaneous AT samples from 296 children (120 girls, 176 boys; ages 0-18; BMI SDS -2.7 to 4.3), and an association with obesity and AT biology was studied. An effect of LDAH on adipogenesis was investigated in SGBS preadipocytes. RESULTS: Minor allele carriers of rs13385191 showed lower AT LDAH expression compared to non-carriers (p < 0.001) and a trend toward higher BMI SDS, which was, however, not statistically significant (p = 0.062). Consistently, study participants with lower LDAH expression showed higher BMI SDS (p = 0.005). A negative correlation was found between LDAH and macrophage infiltration into AT after controlling for age (R = -0.132; p = 0.039), and high LDAH expression was associated with lower circulating TNFα (p = 0.017). LDAH expression increased during SGBS adipocyte differentiation, while its knockdown did not alter differentiation. In line with results from AT, TNFα significantly reduced LDAH expression in SGBS cells (p = 0.009). CONCLUSIONS: LDAH seems to have a role in AT inflammation and the development of obesity in children.
Mogna-Peláez P, Zhang N, Guasch-Ferré M
… +11 more, Milagro FI, Riezu-Boj JI, Herrero JI, Elorz M, Benito-Boillos A, Tobaruela-Resola AL, Marti Del Moral A, Tur JA, Martínez JA, Abete I, Zulet MÁ
OBJECTIVE: Obesity management relies on energy restriction, yet the contribution of dietary quality to weight-loss and body composition outcomes during hypocaloric interventions remains poorly characterized. This study e...OBJECTIVE: Obesity management relies on energy restriction, yet the contribution of dietary quality to weight-loss and body composition outcomes during hypocaloric interventions remains poorly characterized. This study evaluated whether adherence to the Planetary Health Diet (PHD), as a measure of diet quality, and its key components is associated with weight loss and body composition during energy restriction. METHODS: Data from 403 adults with overweight or obesity were analyzed at baseline and at 3, and 6 months across two controlled dietary interventions prescribing a 30% energy deficit. PHD adherence was quantified using an energy-adjusted score based on EAT-Lancet dietary targets. Excellent weight loss was defined as ≥ 10% body weight reduction. Associations were assessed using mixed models, logistic regression, and mediation analyses. RESULTS: Higher PHD adherence was associated with lower BMI, waist circumference, and body fat percentage. Participants in the highest-adherence quartile had lower BMI than those in the lowest-adherence quartile (-0.94 kg/m; 95% CI: -1.62 to -0.31; p = 0.005). Each 10-point increase in adherence increased odds of achieving ≥ 10% weight loss by 49% (OR = 1.49; 95% CI: 1.03-2.16). Red and processed meat reduction and higher whole-grain intake mediated associations. CONCLUSIONS: Greater PHD adherence during energy restriction was associated with greater weight loss and improved body composition. TRAIL REGISTRATION: ClinicalTrials.gov identifiers NCT02737267 and NCT03183193.
Obesity (Silver Spring)
· 2026 Jul · PMID 42159196
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OBJECTIVE: We sought to determine how the proportion of adults historically receiving obesity interventions would be classified under the recently proposed "pre-clinical" and "clinical" obesity classifications and the im...OBJECTIVE: We sought to determine how the proportion of adults historically receiving obesity interventions would be classified under the recently proposed "pre-clinical" and "clinical" obesity classifications and the impact of this change on safety and outcomes. METHODS: A retrospective analysis of adults with BMI ≥ 35 who received bariatric surgery (BS) or antiobesity medications (AOMs) between 2017 and 2023 was conducted using the Merative MarketScan database. Patients had ≥ 6-month continuous enrollment before treatment. Clinical obesity was defined as presence of ≥ 1 obesity-related condition and pre-clinical obesity defined as absence of such. Treatment-related complications were identified within 90 days of treatment initiation. Multivariable logistic regression was used to compare the odds of treatment-related complications by obesity classification. RESULTS: A total of 120,499 individuals (46.1%) underwent BS and 140,909 (53.9%) received AOMs. Among BS patients, 12.7% (n = 15,334) had pre-clinical obesity. Of AOM users, 38.1% (n = 53,633) had pre-clinical obesity. Clinical obesity patients were older with a higher comorbidity burden compared to pre-clinical obesity. Clinical obesity was associated with higher odds of post-treatment complications (AOM: aOR 1.10, BS: aOR 1.39, both p < 0.001). CONCLUSIONS: This novel framework would reclassify a significant proportion of patients as having pre-clinical obesity. Use of these definitions to determine treatment eligibility could potentially delay intervention and shift care to older, sicker populations.
Chakraborti Y, Mumford SL, Yeung EH
… +8 more, Grantz KL, Mendola P, Mills JL, Caniglia EC, Brensinger CM, Zhang C, Schisterman EF, Hinkle SN
Obesity (Silver Spring)
· 2026 Jul · PMID 42159037
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OBJECTIVE: This study aimed to evaluate the link between postpartum weight retention (PPWR) and long-term mortality. METHODS: In this secondary analysis of 8165 women with ≥ 2 pregnancies in the Collaborative Perinatal P...OBJECTIVE: This study aimed to evaluate the link between postpartum weight retention (PPWR) and long-term mortality. METHODS: In this secondary analysis of 8165 women with ≥ 2 pregnancies in the Collaborative Perinatal Project (CPP), U.S., 1959-1966, with vital status follow-up through 2016, we used interconception weight change (ICWC) and interpregnancy weight change (IPWC) as proxies of PPWR. ICWC was defined as the difference between self-reported pre-pregnancy weight from the 1st and 2nd CPP pregnancies, while IPWC was the difference between weight recorded at delivery of the 1st and pre-pregnancy weight of the 2nd CPP pregnancies. All-cause and cause-specific mortality models were adjusted for sociodemographic, behavioral, clinical, and pregnancy-related characteristics from the 1st CPP pregnancy. RESULTS: Compared to women with ICWC > 0 to 1.8 kg (quintile 3), those with ICWC > -1.4 to 0 kg (quintile 2) had a lower risk of all-cause mortality (aHR [95% CI]: 0.85 [0.76-0.96]), with the most notable reduction observed in diabetes-related risk of mortality (aHR [95% CI]: 0.45 [0.23-0.87]). Lower quintiles of IPWC (i.e., greater weight loss) were suggestive of reduced all-cause and cause-specific risk of mortality, though the estimates were not statistically significant. CONCLUSIONS: Minimizing PPWR was linked to reduced mortality risk over 50 years of follow-up.
Baeuerle E, Semwal MK, Nie J
… +12 more, Zhang N, Liang H, Ganapathy V, Sathavarodom N, Fernandez R, Wang CP, Espinoza S, Dong Q, Gao X, Yang Z, Kostic A, Musi N
OBJECTIVE: This study evaluated whether two interventions with putative lipopolysaccharide (LPS)-lowering properties, the phosphate binder sevelamer or a synbiotic, improve insulin sensitivity in humans. METHODS: We cond...OBJECTIVE: This study evaluated whether two interventions with putative lipopolysaccharide (LPS)-lowering properties, the phosphate binder sevelamer or a synbiotic, improve insulin sensitivity in humans. METHODS: We conducted a randomized, double-blind, placebo-controlled, three-arm parallel-group trial. Twenty-two lean and twenty-eight participants with obesity completed the trial. Participants were randomized to: (1) sevelamer; (2) synbiotic (oligofructose plus Bifidobacterium longum Rosell-175); or (3) placebo, three times a day for 4 weeks. The primary outcome was change in peripheral insulin sensitivity (M) assessed by hyperinsulinemic (60 mU/m min) euglycemic clamp versus placebo. RESULTS: In participants with obesity, sevelamer improved the M (+2.176 [0.314, 4.038] mg/kg min vs. placebo; p = 0.022) and lowered LDL-C (-29.675 [-53.794, -5.556] mg/dL vs. placebo; p = 0.016). Synbiotic had no effect on insulin sensitivity or lipids in either group. No changes in markers of endotoxemia were observed with any intervention. Sevelamer increased plasma levels of metabolites linked to improved glucose and lipid metabolism, such as bile acids, amino acids (citrulline, betaine), NAD+ precursors (trigonelline), and xenobiotics (genistein, umbelliferone). CONCLUSIONS: Sevelamer improves insulin sensitivity and LDL-C in participants with obesity. Further investigation is warranted to elucidate sevelamer's metabolic mechanisms, potentially involving the mediation of bile acids and other host-microbiome-derived metabolites. TRIAL REGISTRATION: ClinicialTrials.gov NCT02127125.
OBJECTIVE: Monitoring body composition is essential for assessing nutritional status and detecting early muscle loss, yet most methods require clinical settings. This study evaluated a self-assessment model that uses con...OBJECTIVE: Monitoring body composition is essential for assessing nutritional status and detecting early muscle loss, yet most methods require clinical settings. This study evaluated a self-assessment model that uses consumer technologies for personalized and data-driven body composition monitoring. METHODS: We developed a consumer-accessible five-compartment model that integrates body volume from smartphone-based three-dimensional optical imaging with total body water from smartwatch-based bioelectrical impedance analysis. Body volume and total body water were calibrated against air displacement plethysmography and a clinical-grade bioimpedance system, then combined within a five-compartment framework to estimate fat-free mass and fat mass. Estimates from the accessible model were compared with corresponding five-compartment estimates derived from reference laboratory methods using linear regression and root mean square error. RESULTS: In 30 adults, smartphone body volume (r = 0.97, RMSE = 2.65 L) and smartwatch total body water (r = 0.98, RMSE = 1.54 L) showed strong agreement with laboratory measures but required offset corrections to remove biases. After calibration, fat-free mass and fat mass estimates closely matched the laboratory-derived five-compartment model (r > 0.96, RMSE = 2.10 kg). CONCLUSIONS: Properly calibrated smartphones and smartwatches can yield multicompartment body composition estimates that closely match laboratory standards and support precise, low-cost monitoring in remote and resource-limited settings.
Sun X, Mahler C, Stull ND
… +6 more, Nasiri A, Zhou B, Samuel V, Shulman G, Flak JN, Ren H
Obesity (Silver Spring)
· 2026 Jun · PMID 42130095
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OBJECTIVE: Obesity, a major driver for diabetes development, is characterized by insulin and leptin resistance. We previously showed that loss of G protein-coupled receptor 17 (Gpr17) in specific hypothalamic neurons and...OBJECTIVE: Obesity, a major driver for diabetes development, is characterized by insulin and leptin resistance. We previously showed that loss of G protein-coupled receptor 17 (Gpr17) in specific hypothalamic neurons and the intestine led to better energy balance and glucose metabolism. Our goal is to test whether general loss of Gpr17 enhances insulin and leptin sensitivity. METHODS: We generated germline Gpr17 knockout mice on both lean (Gpr17 ) and obese (Gpr17 ; ob/ob) backgrounds and characterized their metabolic profile. RESULTS: Gpr17 mice exhibited increased energy expenditure and oxygen consumption. Euglycemic-hyperinsulinemic clamp studies showed enhanced insulin sensitivity in Gpr17 mice with increased glycogen synthesis and decreased glycolysis. Gpr17 ob/ob mice had increased insulin sensitivity with lower baseline serum insulin and higher response to exogenous leptin treatment with more reduction in feeding and increased pStat3 activation in hypothalamic nuclei. CONCLUSIONS: These findings highlight the inhibitory effect of Gpr17 in leptin and insulin sensitivity, suggesting its potential as a therapeutic target for obesity treatment.
OBJECTIVE: This study compared changes in health care costs and use across cohorts initiating four obesity medications (OMs). METHODS: Commercial insurance claims were used to identify new initiators of phentermine (n = ...OBJECTIVE: This study compared changes in health care costs and use across cohorts initiating four obesity medications (OMs). METHODS: Commercial insurance claims were used to identify new initiators of phentermine (n = 136,788), phentermine-topiramate-ER (n = 13,888), naltrexone-bupropion-SR (n = 28,712), or liraglutide (n = 49,266) for obesity. Multivariable difference-in-differences analyses compared the three newer drugs to phentermine for change in total annual prescription drug and health care costs, outpatient visits, and acute care use (combined emergency department visits and hospital stays). RESULTS: Up to 3 years after OM initiation, prescription and total health care costs were higher for all three newer OM cohorts relative to phentermine, with liraglutide having the greatest comparative increase in annual costs (e.g., total costs 73.6% [70.9%, 76.3%] higher in year 1). Primary care physician visit frequency was slightly lower for the newer OMs (e.g., -12.6% [-13.6%, -11.6%] in year 1 for liraglutide). CONCLUSIONS: The cost of OM treatment, even for medications that preceded highly effective weekly incretin analogues, appeared to increase overall prescription spending and total health care costs. Yet, other than a relative decrease in primary care physician visit frequency, more costly OMs were not associated with favorable changes in health care use patterns compared to generic phentermine. Reductions in OM cost and other interventions to support their longer-term use may be needed to fully realize the promise of these medications.
Lemas DJ, Zapata R, Loy I
… +12 more, Mahadevan A, Wen T, Mkuu R, Louis-Jaques A, Hall J, Harrall KK, Strath L, Sheer A, Shenkman E, Guo S, Cardel MI, Smith S
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed to women of reproductive age for obesity, type 2 diabetes, obstructive sleep apnea, and more. Data on pregnancy outcomes following prepregnan...OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are prescribed to women of reproductive age for obesity, type 2 diabetes, obstructive sleep apnea, and more. Data on pregnancy outcomes following prepregnancy exposure remain limited. We evaluated associations between prepregnancy GLP-1RA exposure and maternal and neonatal outcomes among women with preexisting obesity and diabetes. METHODS: We conducted a retrospective cohort study using electronic health records data. Prepregnancy GLP-1RA exposure was defined by prescription orders within 12 and 24 months prior to delivery. Propensity score matching was performed using maternal age, race and ethnicity, prepregnancy obesity status, diabetes type, chronic hypertension, insurance type, and rurality. Primary outcomes included preeclampsia (PE). Secondary outcomes included cesarean delivery, infant growth, gestational age at delivery, and neonatal intensive care unit length of stay. RESULTS: Among 31 exposed pregnancies, 29 were matched to unexposed controls. GLP-1RA exposure was associated with higher prevalence of PE (12 months: p = 0.023; 24 months: p = 0.018). Cesarean delivery occurred more frequently among exposed pregnancies (p < 0.05). No differences were observed in neonatal outcomes after matching. CONCLUSIONS: Prepregnancy GLP-1RA exposure was associated with higher prevalence of PE and cesarean delivery in this cohort. Larger studies are needed to confirm these findings and clarify underlying mechanisms.
Obesity and its related metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), represent a major global health challenge. Mitochondrial dysfunction is a key driver in their pathogen...Obesity and its related metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD), represent a major global health challenge. Mitochondrial dysfunction is a key driver in their pathogenesis. This review explores the emerging role of mitochondrial transfer, a novel mode of cellular communication that can occur via tunneling nanotubes, extracellular vesicles, or as free mitochondria, in these conditions. Increasing evidence suggests that mitochondrial transfer may contribute to tissue homeostasis and metabolic adaptation, and that disruption of this process may participate in the pathogenesis of obesity and MASLD. In parallel, therapeutic strategies aimed at restoring mitochondrial function by enhancing endogenous mitochondrial transfer or through mitochondrial transplantation are beginning to emerge. This review summarizes current knowledge of the mechanisms underlying mitochondrial transfer, discusses roles in obesity and MASLD, and evaluates the therapeutic potential and translational challenges of targeting mitochondrial transfer in obesity and obesity-related metabolic disease.
de Roo M, Kretschmer T, Llewellyn C
… +2 more, Oliver BR, Hartman CA
Obesity (Silver Spring)
· 2026 Jul · PMID 42112780
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OBJECTIVE: We examined whether genetic risk for higher BMI, parental feeding practices (restriction, pressure to eat, and monitoring), and their interactions were associated with overweight trajectories during adolescenc...OBJECTIVE: We examined whether genetic risk for higher BMI, parental feeding practices (restriction, pressure to eat, and monitoring), and their interactions were associated with overweight trajectories during adolescence. METHODS: Data came from 5568 participants aged 10-18 in the Twins' Early Development Study who had at least one measurement of weight. Parental feeding practices were reported at age 10 using the Child Feeding Questionnaire. A polygenic score for BMI was used as a proxy for genetic risk. We identified overweight trajectories using latent class growth analysis, and associations with genetic risk, feeding practices, and their interactions were tested using multinomial logistic regression with trajectory as the outcome. RESULTS: Three trajectories were identified: non-overweight, persistent overweight, and adolescent-onset overweight. Higher genetic risk and greater parental restriction and monitoring were associated with persistent overweight, whereas pressure to eat was associated with non-overweight. Associations remained after adjustment for general parenting and additional risk factors. We found no evidence for gene-environment interaction. CONCLUSIONS: Genetic risk and parental feeding practices were independently associated with adolescent weight development. While this suggests feeding practices may be relevant targets for prevention, the findings likely represent complex bidirectional parent-child dynamics.
OBJECTIVE: This study aimed to quantify the impact of adolescents' exposure to unhealthy food marketing in real-world digital environments. METHODS: We conducted a single-blinded randomized field experiment including 121...OBJECTIVE: This study aimed to quantify the impact of adolescents' exposure to unhealthy food marketing in real-world digital environments. METHODS: We conducted a single-blinded randomized field experiment including 121 Australian adolescents aged 16-17. A latent class analysis was used to identify personas, and participants were randomized (1:1) to an intervention or control group. Using retargeting pixels, the intervention group was exposed to advertisements for a fictitious sugar-sweetened beverage "Clu" embedded in their feed for 2 weeks. The control group was not exposed to Clu advertisements. An exit survey collected data on purchase intention for Clu. Exposure effect on purchase intention was estimated using logistic regression, reported as a risk ratio. RESULTS: An intention to purchase Clu was reported by 26.2% of participants (n = 16) in the control and 71.6% in the intervention group (n = 43). Participants in the intervention group were 2.73 times more likely to report intention to purchase Clu than those in the control (RR = 2.73; 95% CI: 1.74-4.28). CONCLUSIONS: Social media advertisements for sugar-sweetened beverages significantly influence adolescents' purchase intentions of the beverages, highlighting digital advertising as a modifiable commercial determinant of dietary risks. These findings underscore the need for policy interventions that address unhealthy food digital marketing to reduce obesity-related behaviors among adolescents.
OBJECTIVE: This study aimed to investigate whether the time of the eating window during time-restricted eating (TRE) alters the gut microbiota and metabolomic profiles and to determine their relationship with cardiometab...OBJECTIVE: This study aimed to investigate whether the time of the eating window during time-restricted eating (TRE) alters the gut microbiota and metabolomic profiles and to determine their relationship with cardiometabolic risk factors in adults with overweight or obesity. METHODS: In an 8-week randomized controlled trial, 60 young adults with overweight or obesity were randomized to 6-h eTRE (7 a.m.-1 p.m.), 6-h lTRE (12 p.m.-6 p.m.), or a control group (ad libitum). The gut microbiota was analyzed by 16S ribosomal RNA (16S rRNA) sequencing and serum metabolomics were quantified by liquid chromatography-mass spectrometry (LC-MS). RESULTS: After 8 weeks, compared to the control group, the 6-h eTRE increased abundance of Faecalibacterium and Lactobacillus and decreased abundance of unclassified_f_Peptostreptococcaceae, whereas 6-h lTRE significantly increased abundance of Faecalibacterium and decreased abundance of Shigella (all p < 0.05). Differential serum metabolites (e.g., L-malic acid in eTRE; isovaleric acid in lTRE) were significantly associated with changes in weight, body fat, and systolic blood pressure (SBP) (p < 0.05). CONCLUSIONS: Time-restricted eating may be beneficial to weight loss and cardiometabolic health improvement by regulating gut microbiota and serum metabolites. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039115.