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...

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...

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...

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...

Uric acid (UA) is traditionally regarded as a metabolic risk marker; however, its dynamic behavior during glucose-lowering therapy remains incompletely understood. We compared UA responses to a modified traditional Japanese diet (MJDD) and the DPP-4 inhibitor alogliptin in patients with early-stage type 2 diabetes mellitus (T2DM). In this prospective observational study, drug-naive patients received MJDD (n=58) or alogliptin (n=52) monotherapy for 3 months. Changes ({Delta}) in serum UA were ana...

IntroductionDysglycemia is a well-established risk factor for cardiovascular disease (CVD); yet traditional glycemic traits, including fasting plasma glucose (FPG) and HbA1c, do not capture dynamic glucose fluctuations that may inform CVD risk. We cross-sectionally investigated the association of continuous glucose monitor (CGM)-derived metrics and 2-h post-prandial glucose (2-h PPG) with estimated 10-year CVD risk among individuals without diabetes. MethodsWe included 1,360 Framingham Heart St...

BackgroundOverweight and obesity are causing growing public health, economic and clinical burden, particularly within under-resourced communities. There is an urgent need to develop an in-depth understanding of experiences of weight management, and preferences for support within under-resourced communities, with a view to developing more effective weight management interventions. MethodsFocus groups were run in under-resourced communities using storyboarding; a method to facilitate inclusive co...

ContextPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with reproductive dysfunction and long-term cardiometabolic risk. Traditional phenotype classifications based on diagnostic criteria may not fully capture the multidimensional biological variability underlying endocrine and metabolic risk profiles, particularly in young women. ObjectiveTo identify data-driven endocrine-metabolic phenotypes in young women with PCOS and evaluate their association with establi...

ObjectiveTo introduce and evaluate the clinical utility of the "adipo-B index" as a novel metric of the adipose tissue-pancreatic beta cell axis. To our knowledge, no prior clinical metric has integrated adipose tissue insulin resistance and pancreatic beta-cell function into a single index applicable across therapeutic classes. MethodsTreatment-naive subjects with T2DM received monotherapy with modified traditional diet for diabetes (MJDD, n=61), canagliflozin (n=67), pioglitazone (n=54), or s...

AimsThis study aimed to examine the prevalence of malnutrition and its associations with functional capacity and quality of life (QoL) in AL and ATTR cardiac amyloidosis patients. Methods and ResultsThis cross-sectional pilot study included 29 patients with confirmed CA (14 AL, 15 ATTR). Data were collected between January 2020 and September 2021. Nutritional status was assessed using body mass index (BMI), anthropometric measures, and the Subjective Global Assessment (SGA). Functional capacity...

The gut microbiota has been implicated in regulating body composition, insulin resistance, and energy metabolism through microbial metabolites, including short-chain fatty acids (SCFAs) and amino acids. However, evidence in adolescents, particularly regarding sex-specific differences and lifestyle such as alcohol intake, remains limited. Characterizing sex-specific metabolic signatures in adolescence may improve early identification of metabolic risk. To address this gap, we investigated associ...

ObjectivesTo examine associations between cardiometabolic conditions and health-related quality of life (HRQoL) and to evaluate whether condition-associated HRQoL changed from 2001 to 2022. MethodsWe analyzed nationally representative data from U.S. adults aged [&ge;]18 years in the Medical Expenditure Panel Survey, 2001-2022. Survey years without BMI data (2017, 2019, 2021) were excluded. EQ-5D utilities were mapped from SF-12 scores using a validated algorithm. For each survey year, survey-we...

Cushings disease is caused by the overproduction of cortisol. The effects of this disease are well known in a general population, including high blood pressure, diabetes, and weight gain. Cushings disease causes both obesity and metabolic related symptoms, and it can be difficult to discern the obesity-dependent from the obesity-independent mechanisms of Cushings disease. To identify patients with Cushings disease, we identified 476 Michigan Medicine patients between January 1st 2000-2025 along ...

BackgroundSex hormone alterations, such as estrogen deficiency or testosterone excess, substantially increase cardiovascular disease (CVD) risk in females. Dietary fibre and its microbial by-products, short-chain fatty acids (SCFAs), have cardioprotective effects, but it remains unclear whether these benefits extend to females with an altered sex hormone profile. In this study, we aim to investigate whether dietary fibre intake, measured via plasma acetate--the most abundant SCFA--is associated ...

Background and AimsThe glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has demonstrated efficacy for the secondary prevention of cardiovascular disease among patients with overweight/obesity without diabetes mellitus. However, the comparative effectiveness of GLP-1 RA versus other antiobesity medications (e.g. phentermine-topiramate) not been evaluated. MethodsThis was a retrospective, observational, cohort study using target trial emulation methodology using the Truveta electro...

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aim...