International Journal of Obesity

IntroductionMechanistic research has shown that prior obesity induces durable transcriptomic and epigenetic reprogramming in adipose tissue that persists after weight loss and predisposes individuals to weight regain. This phenomenon, termed obesogenic memory (OM), is currently conceptualized primarily as a molecular process. We propose extending OM beyond adipose tissue biology to include interacting biological and sociocultural processes through which past exposures shape present physiological...

BackgroundCaloric restriction (CR) improves markers of biological aging, yet long-term effects on the human metabolome remain unclear. ObjectiveThis study examined the effects of CR (2 years) in healthy adults without obesity on circulating metabolites linked to aging and metabolic adaptations. MethodsUntargeted metabolomics was performed using fasted plasma samples collected at baseline, 12, and 24 months (BL, 12M, 24M) from CALERIE participants randomized to CR or ad libitum (AL) control. A ...

Societies are aging rapidly in parallel with the increasingly earlier onset of serious diseases in younger populations. These and other factors are creating a substantial disparity between healthspan, the period of life where an individual is free from serious chronic disease or disability, and lifespan -- expanding the morbidity span. Extending healthspan has thus become a major priority. To pursue an integrated strategy toward healthspan support, we launched DELTA, a prospective, open-label, i...

Opioid use disorder (OUD) has been linked to cardiometabolic diseases in adults through reductions in adiponectin--an adipocytokine with insulin-sensitizing effects. Opioid use during pregnancy dysregulates neonatal growth and may predispose to adult-onset diseases, but the impact of maternal OUD on neonatal adiponectin has not been studied. We hypothesize that maternal OUD also reduces adiponectin level in offspring (primary outcome) and alters growth (secondary outcome). To test our hypothesis...

BackgroundDigital health self-monitoring tools are widely used to support weight management and metabolic health. Higher engagement with these tools is often associated with better clinical outcomes; however, real-world engagement-outcome relationships for consumer metabolic monitoring devices remain incompletely characterized, particularly in heterogeneous user populations. ObjectiveTo evaluate whether engagement with a portable breath-based metabolic device (Lumen; Metaflow Ltd.) is associate...

Poor sleep is linked to consumption of sugary foods/beverages and high neural responsivity to palatable food cues. Yet, whether hedonic liking for sweet taste explains these associations remains unclear. We examined cross-sectional associations of five sleep traits (chronotype, sleep duration, insomnia frequency, snoring, daytime dozing) and a composite sleep score with sweet food liking, and total and free sugar intake in 76,734 UK Biobank participants (39-72 years, 56.3% female). Models adjust...

Obesity and metabolic dysfunction are among the strongest risk factors for poor brain and mental health, yet the neural mechanisms linking metabolism, brain, and behaviour remains poorly understood. Here, we provide the first evidence for two distinct large-scale brain network configurations--one associated with metabolic health and another with obesity-- identified using resting-state fMRI data and metabolic phenotypes from a large community cohort (N = 564). While obesity was linked to enhance...

Background and aimsThe optimal eating window for time-restricted eating (TRE) remains unclear. We investigated the effects of 8-hour TRE combined with usual care (UC, a Mediterranean diet-based education program), versus UC alone over 12 weeks on hepatic fat fraction, liver health markers, and fecal microbiota in adults with overweight or obesity. MethodsIn this multicenter randomized trial, participants (50% women) were assigned to UC (n=49), early TRE (n=49), late TRE (n=52), or self-selected...

BackgroundEvidence on how leisure-time physical activity (LTPA) improves lifetime body mass index (BMI) remains fragmented and prone to confounding. MethodsWe pooled 14,993 adults (30-90 y; 52.7% women; cohorts: REGICOR-ACRISC, ILERVAS, ARTPER) with baseline estimated LTPA (moderate-to-vigorous LTPA [MVLTPA] in REGICOR-ACRISC), genotype, and repeated BMI values from electronic health records (1990-2024, 36,157 measures). LTPA was categorized into cohort-specific quartiles; MVLTPA in 0, <100, <2...

PurposeBody dissatisfaction is common, particularly among those with higher BMIs. Issues with BMI as an adiposity measure may limit our understanding of body dissatisfaction determinants. We investigate the association of childhood trajectories of BMI, fat mass index (FMI), and fat-free mass index (FFMI) with body dissatisfaction at age 14, and sex differences in these associations. MethodsWe used latent class growth analysis to model trajectories of BMI (3-14 years), FMI and FFMI (7-14 years) ...

ImportanceInfants born small or large for gestational age exhibit different growth patterns compared with appropriate-for-gestational age counterparts. Evidence is lacking on how birth weight centiles beyond conventional thresholds predict early life growth. ObjectiveQuantify association of birth weight centile range with infant and child growth. DesignProspective cohort study. SettingFrance, Netherlands, Portugal, Singapore, United Kingdom, United States. ParticipantsSingletons from seven b...

BACKGROUNDCardiovascular disease (CVD) is a leading cause of diabetes-related mortality in Mexico. Although diabetes subgroups capture underlying disease heterogeneity, their association and utility for risk prediction for fatal CVD in Mexican adults remain unclear. METHODSWe analyzed 24,943 adults with diabetes from the Mexico City Prospective Study. Participants were classified into mild obesity-related (MOD), severe insulin-deficient (SIDD), severe insulin-resistant (SIRD), and mild age-rela...

BackgroundTime-restricted eating (TRE) has gained popularity for weight loss and metabolic health. While some evidence suggests greater benefits when TRE aligns with circadian rhythms--characterized by early daytime eating and avoidance of nighttime intake, often referred to as early TRE (eTRE), other studies report no meaningful differences between eTRE, other TRE approaches with or without exercise, or calorie restriction (CR), and robust comparative evidence remains limited. AimTherefore, th...

GLP-1 receptor agonist (GLP-1RA) discontinuation has been associated with weight regain. However, the real-world association between discontinuation of GLP-1RA prescriptions and weight change has not been explored. We assessed weight trajectories of 4,182 patients in the six months following their last GLP-1RA prescription. Approximately two-thirds of patients showed stable weight or continued weight loss during this period post the last known GLP-1RA prescription. In a representative subset of ...

BackgroundThe body roundness index (BRI), calculated from height and waist circumference, is a novel obesity metric proposed as an alternative to body mass index (BMI). Although the BRI is reportedly associated with mortality risk, little is known about how the performance of the BRI and BMI compare. MethodsWe used data from the SKDB, a regional healthcare database in Shizuoka, Japan, that includes data from >2 million people from 2012 to 2022. Individuals aged 40 to 74 years who received a Spe...

BackgroundVisceral adiposity is widely regarded as the pathogenic component of central obesity in cardiometabolic disease. However, emerging evidence suggests that abdominal subcutaneous adiposity may also confer metabolic risk in South Asian populations, although data in young, lean individuals are scarce. We investigated associations of MRI-measured abdominal subcutaneous adipose tissue (ASAT) and visceral adipose tissue (VAT) with cardiometabolic risk markers in young rural Indian adults. Me...

The melanocortin 4 receptor (MC4R) plays a critical role in the central control of energy homeostasis and its disruption causes severe early onset obesity. The MC4R agonist Imcivree has been approved for the treatment of certain genetic obesity syndromes. Here we demonstrate that the membrane-spanning protein Attractin-like protein 1 (ATRNL1) directly interacts with MC4R to amplify its signaling in cells and that expression of ATRNL1 potentiates the activation of MC4R neurons by MC4R agonists in...

BackgroundPrediabetes is associated with an increased risk of progression to type 2 diabetes. While dietary interventions in prediabetes traditionally primary focus on energy and macronutrient intake, the role of eating timing has recently been highlighted. This study aimed to examine the relationships between components of eating timing patterns and glycaemic parameters in prediabetes. MethodsIn 297 individuals with prediabetes, i.e. impaired fasting glucose or impaired glucose tolerance (age ...

BackgroundThe role of adipokines in childhood glycemia is poorly understood. We investigate the longitudinal association between adipokines and glycemia in a cohort of children in Mexico City. MethodsChildren from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort (948 children, 52% male) were followed longitudinally from birth. Leptin, adiponectin, glucose, and HbA1c were measured at four, six, and eight years, and fasting insulin at eight years. A...

Obesity-driven type 2 diabetes (T2D) is characterized by pathological alterations in visceral white adipose tissue (vWAT). While microRNAs (miRNAs) are key post-transcriptional regulators, comprehensive human vWAT profiling across metabolic states remains limited. This study characterized vWAT miRNA expression in lean, obese, and obese+T2D individuals to identify regulatory networks associated with metabolic failure. Deep miRNA sequencing was performed on vWAT samples from a discovery cohort, fo...