Plenty of epidemiological studies have focused on obesity and allergic diseases, less is known about the interaction of the comorbidity. The present study was conducted to identify the relationship between obesity and allergy and to clarify the potential regulatory roles of gut microbiota in the development of comorbidity. Four-week-old male BALB/c mice were used to establish the comorbidity model. The high-fat diet was used to induce obese mice, and ovalbumin was used to induce allergic mice. The post-obesity allergy mice and post-allergy obesity mice (n = 12/group) were used to clarify the effects of obesity on allergic reactions and those of allergy on metabolic function. Changes in gut microbiota, short-chain fatty acids (SCFAs), bile acids (BAs), the expression of the SCFAs and the BAs receptors were also detected. In the post-obesity allergy study, the serum Immunoglobulin E and the splenic CD4+CD25+FOXP3+ T cells (Tregs) in post-obesity allergic mice were higher than that in allergic mice. Post-obesity allergic mice had higher abundance of Alistipes, Parabacteroides, Rikenellaceae_RC9_gut_group, Colidextribacter, Muribaculum, Lachnospiraceae_NK4A136_group, and Erysipelatoclostridium but lower levels of SCFAs and expressions of GPR41 and 43. In the post-allergy obesity study, OVA-induced allergy alleviated fat accumulation and glycolipid metabolism disorder in obese mice. However, there was no significant difference in the gut microbiota and the SCFAs receptors between post-allergy obese mice and obese mice, except for BAs. The post-obesity allergy model suggested that early obesity impaired allergic reaction and immune function, which aggravated the development of allergy via altering the composition of the gut microbiota and the contents and function of SCFAs. The post-allergy obesity study suggested that early allergy did not promote metabolic disorder, instead of alleviating the development of obesity, and BAs may contribute to this alleviation.
To examine changes in monocyte subpopulations and surface markers in people with obesity before and after bariatric surgery, and their relation to weight loss, inflammation markers, and comorbidities. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with obesity designated for bariatric surgery at three different time points: before surgery (=baseline), six months and twelve months after the intervention. PBMCs were analyzed using flow cytometry to distinguish the different monocytic subpopulations. At each visit, anthropometric measures and routine laboratory parameters (e.g., C-reactive protein) have been determined. 111 individuals with obesity (59.5% female, mean age 45.2±11.3 years) with a median body mass index (BMI) of 48.4 kg/m2 were included into this study. Median weight loss was 44.5 kg. The absolute monocyte count decreased significantly after surgery within twelve months (p = 0.0035). Classical monocytes, non-classical monocytes, intermediate monocytes, and monocytic myeloid-derived suppressor cells (M-MDSC) decreased significantly after the surgical intervention within six to twelve months. CD14bright/CD56+ monocytes did not change significantly during twelve months of observation. Surface expression of CD14 increased in both classical and intermediate monocytes (p = 0.0272 and 0.0087, respectively) within 6 months whereas CD16 declined across all monocyte subpopulations at every time point. The total monocyte counts as well as numbers of non-classical monocytes were significantly higher in patients with obesity and type 2 diabetes mellitus. COVID-19 containment measures resulted in a longitudinal reduction in the number of patient evaluations. Following bariatric surgery and the resulting weight loss, the obesity-associated perturbation of the monocyte compartment was largely reversed. Normalization of both the total monocyte pool and of monocyte subpopulations, particularly those with pro-inflammatory properties such as intermediate monocytes, could contribute to a risk reduction of known co-morbidities of obesity such as chronic inflammation, impaired glucose regulation, and an increased risk of cancer.
Maternal prepregnancy body mass index (ppBMI) and gestational weight gain (GWG) are risk factors for overweight and obesity (OWO) in childhood. However, a better understanding of the magnitude, timing, and mediating mechanisms of these associations can inform interventions to improve maternal and child health. We conducted a prospective cohort study of 2899 mother-child dyads in northern Virginia (2012-2019). Maternal ppBMI was self-reported and GWG was calculated and categorized as excess (EGWG) using 2009 Institute of Medicine guidelines. Child weight was reported by parents every six months from birth to 24 months, and annually thereafter. Childhood OWO was defined as >85th percentile of WHO growth charts at 36 months. Generalized linear and mixed models estimated maternal OWO status and GWG as predictors of children's body weight Z-score and growth velocity, adjusted for covariate. Causal mediation analysis was used to quantify birth weight and early growth velocity as intervening factors. Mothers self-reported Hispanic (32.08%) and non-Hispanic (51.98%) ethnicity (15.94% missing). Mean ± SD ppBMI was 25.5 ± 5.4 kg/m² (35.46% with obesity) and GWG was 14.2 ± 6.8 kg (40.8% EGWG). At 36 months, 25.4% of children had overweight and 10.5% had obesity. Higher ppBMI (RR = 1.04 per 1.00 kg/m2; 95% CI: 1.03-1.06) and GWG was associated with childhood risk of OWO among non-Hispanic but not Hispanic mothers (interaction P = 0.02). Similarly, maternal obesity status (RR = 1.64; 95% CI: 1.26-2.13) and EGWG (RR = 1.38; 95% CI: 1.09-1.74) were associated with childhood OWO risk. Approximately 26.8% (95% CI: 14.9%-55.9%) of the ppBMI-OWO association could be attributed to birth weight. Maternal ppBMI and GWG were independently associated with risk of OWO in early childhood OWO, with variations by child age and ethnicity, highlighting the potential of pre- and perinatal interventions to reduce childhood obesity risk.
The Japanese Working Group on Sarcopenic Obesity (JWGSO) recently published diagnostic criteria for sarcopenic obesity specific to Asian populations. This study aimed to estimate the prevalence and evaluate the characteristics and validity of sarcopenic obesity as defined by the JWGSO. We analysed longitudinal data from 736 community-dwelling older adults aged ≥65 years from the 2012 Otassha Study. Sarcopenic obesity was diagnosed using JWGSO and European Society for Clinical Nutrition and Metabolism/European Association for the Study of Obesity (ESPEN/EASO) criteria. Physical function, body composition, gonalgia, and mobility were compared between participants with and without sarcopenic obesity according to each criterion. Agreement between JWGSO-defined sarcopenic obesity and conventional sarcopenia with obesity or ESPEN/EASO definitions was evaluated using Cohen's kappa coefficient. Survival over approximately an 8-year follow-up was evaluated using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were applied, and when the proportional hazards assumption was violated, analyses were stratified into early and late follow-up periods. Sarcopenic obesity was present in 57 participants (7.7%) per JWGSO criteria and 55 participants (7.5%) per ESPEN/EASO criteria. Regardless of definition, participants with sarcopenic obesity were older; had lower walking speed, grip strength, and balance; and exhibited higher prevalence of conventional sarcopenia, knee osteoarthritis, and reduced mobility function (p = 0.022 to p < 0.001). Agreement between JWGSO and conventional sarcopenic obesity and ESPEN/EASO definitions was fair (K = 0.345) and substantial (K = 0.671), respectively. JWGSO-defined sarcopenic obesity was not significantly associated with mortality in the early follow-up but was linked to increased mortality risk in the late period (HR 3.75, 95% CI 1.66-8.50, p = 0.002). Sarcopenic obesity defined by the JWGSO is distinct from conventional sarcopenia with obesity and ESPEN/EASO-defined sarcopenic obesity. This population-specific criterion may improve identification of older Japanese adults at higher risk of poor physical function and mortality, although further validation is warranted.
Obesity imposes dysfunction of the endogenous cellular reparative system, which may manifest as impaired adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) function or altered characteristics of circulating endothelial progenitor cells (EPCs). However, whether both systems are abnormal in patients with obesity remains unclear. We hypothesized that human obesity induces impairment of MSCs and EPCs that would be reversed after weight-loss surgery (WLS). Abdominal adipose tissue and peripheral blood mononuclear cells were collected to harvest MSCs and EPCs, respectively, from patients with obesity (n = 8) before and 9-12 months after WLS. MSCs mitochondrial function and EPCs number and surface markers were compared to those collected from healthy controls (HC). Patients with obesity had a higher basal body mass index compared to both HC (P < 0.0001) and post-WLS (P < 0.001). Compared to HC, MSC proliferative and differentiation capacity was preserved (P > 0.05), but they showed at baseline increased mitochondrial oxidative stress, and cytochrome-c release (P < 0.05), with reduced membrane potential and matrix density, which mostly improved after WLS. The percent of circulating CD34+KDR+CD133+ and CD34+KDR+ EPCs was elevated in patients with obesity (P < 0.05), as were EPC fractions expressing the inflammatory marker VAP-1 or pro-calcinogenic marker OCN-1, yet neither fell after WLS (P > 0.05). Obesity impairs MSC mitochondrial function and increases the percent of circulating, but also potentially injurious EPCs. WLS largely reverses MSC mitochondrial injury and but not circulating EPC characteristics. Therefore, restoration of the endogenous tissue-resident and circulating cellular regenerative systems in the same patients with obesity may require different strategies or timeframes.
Having obesity is a risk factor for cognitive decline and dementia. It remains unclear whether timing of obesity during someone's lifespan affects this association. To study the association of body mass index (BMI), waist circumference (WC), and having (abdominal) overweight and obesity with cognitive function and decline, and whether these associations were modified by age. 3873 participants (aged 45-70 at baseline, 52% women) from the Doetinchem Cohort Study were included, with up to six repeated measures. Participants were classified as having (abdominal) obesity if they had a BMI ≥30 kg/m² or WC ≥102 cm (men) or ≥88 cm (women). Domain scores for global cognition, memory, flexibility, and processing speed were calculated by standardizing individual test scores at baseline. Associations of time-dependent BMI, WC, and (abdominal) overweight and obesity with cognitive function and decline were studied using linear mixed models. Models were sex-stratified and adjusted for socio-demographic, lifestyle, and mental health factors. Modification by age (≤ or >55 years at baseline) was evaluated using interaction terms. Higher BMI and WC were associated with worse level of cognition (all domains). For both sexes, the smallest difference was for global cognition (BMI) and processing speed (WC), the largest for flexibility (BMI) and memory (WC). Furthermore, having (abdominal) obesity, compared to a healthy BMI/WC, was consistently associated with worse memory function in both sexes. Effect sizes were generally larger for categorical WC compared to categorical BMI. In men, abdominal obesity was associated with accelerated decline in processing speed (all ages), and with accelerated decline in global cognition and flexibility ( > 55 years). In both sexes, higher BMI and WC were consistently associated with worse cognition. WC-based overweight and obesity showed larger effect sizes with cognition than BMI-based overweight and obesity. Only in men, associations with cognitive decline and effect modification by age were observed.
Individuals with excess body weight do not share the same risk for cardiovascular disease (CVD). The phenotype of metabolically healthy obesity (MHO) has drawn the attention of the scientific community due to a potentially reduced CVD risk compared with the phenotype of metabolically unhealthy obesity (MUO). A prospective cohort study was conducted involving 3042 participants from the Attica region in Greece. Baseline demographic, clinical, and lifestyle characteristics were assessed, with participants categorized by their obesity and metabolic health status. Cox proportional hazards models were used to analyze the association between obesity/metabolic health status and 20-year CVD incidence, adjusting for relevant covariates. The sample at baseline comprised 38% individuals who were metabolically healthy without obesity (MHWO), 44% individuals who were metabolically unhealthy without obesity (MUWO), 6% individuals with MHO, and 12% individuals with MUO. Over the 20-year follow-up, 718 participants experienced a CVD event; participants with MUO demonstrated the highest incidence rate (61.1%). Cox regression analyses revealed that individuals with MUO had an 85% higher risk of developing CVD compared with individuals having the MHWO phenotype (HR = 1.85, 95% CI = 1.02-3.58). Individuals with MHO had a 39% elevated risk compared with individuals having the MHWO phenotype (HR = 1.39, 95% CI = 1.06-3.42). Groups with MHO and MUO had independently increased CVD risk, even after multivariable adjustment. Individuals with MUO exhibit the highest risk, but individuals with MHO also have an independently increased CVD risk, emphasizing the significant impact of both obesity and metabolic health status on long-term CVD incidence.
This study aimed to evaluate long-term effectiveness of metabolic and bariatric surgery (MBS) over a 10-year period, to identify predictors of therapeutic success and weight loss, and to compare differences between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A retrospective cohort study was conducted on patients who underwent MBS between 2010 and 2013 at a Portuguese tertiary hospital (n = 909). Patients who underwent laparoscopic adjustable gastric banding or revisional surgery during follow-up were excluded (n = 280). The 10-year loss to follow-up rate among included participants was 37.2% (n = 147). Clinical data were collected over a 10-year period. Therapeutic success was defined as a percentage excess weight loss (%EWL) of at least 50%. Multivariate logistic or linear regression analyses were performed to identify independent predictors of long-term outcomes. Of 395 participants included, 89.6% were females, with a mean age of 41.9 ± 10.8 years and a median body mass index (BMI) of 43.8 [40.9; 47.8]Kg/m2; 88.1% underwent RYGB. After 10.0 ± 1.30 years, the mean weight loss was 31.0 ± 14.4 kg, corresponding to a percentage of total weight loss (%TWL) of 26.4 ± 11.0% and %EWL of 61.9 ± 26.6%. Therapeutic success was achieved by 70.6% of patients, and 39.0% lost at least 30.0% of baseline weight. Eighteen patients (4.55%) lost less than 5%. RYGB was associated with higher odds of long-term therapeutic success compared to SG (OR = 2.158 [95% CI 1.083-4.303], p = 0.029). Weight loss at one year also predicted long-term success (OR = 1.111 [95% CI 1.075-1.149], p < 0.001), while a higher BMI predicted lower %EWL (β = -1.684 [95% CI: -2.366 to -1.001], p < 0.001). MBS remains an effective long-term treatment for obesity, with RYGB offering superior outcomes compared to SG in our cohort. Our findings highlight the importance of early postoperative weight loss, and baseline BMI as key predictors of long-term outcomes and success after bariatric surgery.
Chronic obesity is associated with impaired bone health. However, few investigations have been conducted to assess bone physiology in early-onset obesity. In this study, we measured specific bone turnover and metabolic biomarkers in children with severe obesity with biallelic loss-of-function variants of the leptin (LEP), leptin receptor (LEPR), or melanocortin 4 receptor (MC4R) genes. Thirty-nine children aged 0.3-8.8 years with a BMI SDS ≥ 3, previously identified with pathogenic variants in LEP, LEPR, or MC4R, were recruited for the current study. Additionally, 13 age-matched children with severe obesity who tested negative for variants in known obesity-related genes were included, and another 13 unrelated age-matched children with normal body weight served as the control group. Serum osteocalcin, osteopontin, osteoprotegerin, and sclerostin levels were assessed using multi-analyte profiling. Serum leptin, insulin, and cortisol levels were determined using ELISA. Serum levels of osteocalcin and osteopontin, specific markers of bone formation, were significantly lower in children with LEP and LEPR biallelic variants than in the control group. In contrast, the values of these two biomarkers in children with MC4R deficiency were significantly higher than those in the other groups. No differences were observed in the bone resorption markers osteoprotegerin and sclerostin. Hyperleptinemia was more pronounced in children with LEPR deficiency. Serum insulin concentrations were elevated in individuals with MC4R deficiency, whereas serum cortisol levels were significantly higher in children with LEP deficiency than in all other groups. Our data demonstrate that osteogenic activity (but not resorption activity) is differentially affected in children with complete genetic disruption of the leptin-signaling pathway. Children with MC4R deficiency showed higher osteogenic markers, but children with LEP and LEPR deficiencies showed the opposite. Our results support the usefulness of bone turnover biomarkers for the assessment and management of bone health in different types of obesity.
Obesity is common among people with epilepsy and is influenced by genetic susceptibility, lifestyle behaviours, and antiseizure medications (ASMs). How ASMs and lifestyle factors interact with genetic risk for obesity in epilepsy remains unclear. This population-based cohort study analysed UK Biobank participants with epilepsy recruited between 2006 and 2010. Polygenic risk scores for body mass index (PRSBMI) classified individuals into low, medium, and high genetic risk groups. Associations between commonly used ASMs-including lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), and levetiracetam (LEV)-and overweight/obesity were examined using multivariable logistic regression, adjusting for demographic, socio-economic, and lifestyle factors. Gene-drug interactions were assessed, and Mendelian randomisation (MR) was used to explore potential links between LTG target gene expression and BMI. A total of 8451 individuals were included. In multivariable logistic regression analyses, LTG use was associated with lower odds of obesity (OR = 0.63, 95% CI: 0.47-0.85, P = 0.002) and overweight (OR = 0.72, 95% CI: 0.56-0.92, P = 0.014). VPA was associated with an increased obesity risk (OR = 1.31, 95% CI: 1.07-1.60, P = 0.010). Subgroup analysis suggested that LTG use was associated with a lower risk of obesity, particularly among individuals with low to moderate PRSBMI. As PRSBMI increased, the absolute difference in overweight risk between LTG users and non-users decreased. Sex-stratified analyses showed that LTG had a more substantial protective effect in males, while VPA was more strongly associated with obesity risk in females. Lifestyle factors were significantly associated with obesity and overweight risk, with higher physical activity levels and adherence to a healthy diet being associated with lower risk. MR analysis suggested a potential causal relationship between LTG target gene expression and BMI. Genetic predisposition, ASMs, and lifestyle behaviours were collectively associated with the risk of overweight and obesity in epilepsy. LTG use was associated with a lower risk of weight gain, particularly among individuals with lower genetic susceptibility, with this association attenuating as genetic risk for obesity increased. VPA was associated with an increased risk of obesity, especially in females. These findings support personalised metabolic risk management in epilepsy care.
While weight loss often triggers adaptations to prevent further weight loss, these remain understudied and under-considered in the context of pediatric obesity. This systematic review and meta-analysis is the first to provide a comprehensive synthesis of the available evidence regarding the adaptations of the components of total energy expenditure (EE) in response to weight loss in children and adolescents with overweight/obesity (OW/OB), considering the intervention types (e.g., dietary, multidisciplinary, pharmacotherapy, bariatric surgery, or physical activity-based). Articles reporting on weight loss interventions of any type that included an assessment of EE based on indirect calorimetry were identified through a search of MEDLINE, EMBASE, and COCHRANE databases up to September 2024. Of the initial 1723 references found, 31 were included, representing 53 intervention arms. The meta-analysis revealed a small but non-significant decrease in resting EE (REE) after weight loss (Mean Change (MC) = -130.91 [-492.67, 230.86] kJ, p = 0.467), regardless of the intervention type. However, the systematic review suggests that the degree of weight loss and multidisciplinary studies (particularly those involving caloric restriction) appear to result in a greater decrease in REE, especially in girls, and during short-term interventions. REE relative to fat-free mass (FFM) (MC = -0.95 [-6.11, 4.21] kJ.kg-1, p = 0.700) and physical activity-induced EE (PAEE) (MC = 45.47 [-22.93, 113.87] kJ, p = 0.155) were not meaningfully altered. The heterogeneity of the proposed intervention duration and the high inter-individual variability in body weight and composition changes could have contributed to these modifications. The present results highlight the need for further well-controlled and designed studies, especially when it comes to the thermic effect of food, and the need to consider the patients' individual profiles and responses to interventions.
Obesity has traditionally been defined using body mass index (BMI), but this may overlook central adiposity and related metabolic risks. In 2025, new guidelines recommended adding anthropometric measures. This study analyzed obesity prevalence comparing definitions and their associations with cardiovascular and metabolic diseases. Using a population-based study in Geneva, Switzerland (2005-2024), we measured the prevalence of obesity based on the traditional and new definitions. Reclassification patterns were examined, and associations with diabetes, hypertension, and dyslipidemia were assessed via logistic regression and receiver operating characteristic analyses. Among 14,658 individuals (mean age 48.2 ± 13.7; 51.4% women), obesity prevalence ranged from 10.8% to 39.9% using new classifications, compared to 13.1% with BMI alone (p < 0.001). Reclassifications differed among men and women and with age. New classifications demonstrated superior discriminative performance for the detection of cardiovascular and metabolic outcomes compared to BMI alone. BMI + waist-to-hip ratio showed the strongest associations with diabetes (aOR 4.61; 3.87-5.47), and hypertension (aOR 3.61; 3.18-4.09), while waist-to-hip and waist-to-height ratio showed the strongest association with dyslipidemia (aOR 1.95; 1.75-2.16). Adding anthropometric measures to BMI substantially improves obesity detection. Choosing the combination of anthropometric measures and BMI with awareness of sex and age-related changes better identifies at risk individuals. This new definition can be a powerful low-cost tool in detecting individuals on the obesity spectrum early in primary care settings and prevent complications.
Mitochondria, the cell's powerhouse, play a central role in energy homeostasis and may influence obesity risk. Variations in mitochondrial DNA (mtDNA) have been hypothesized to influence early-life metabolic programming; however, prospective evidence remains limited, and no study has jointly examined multiple mtDNA biomarkers. We aimed to investigate the individual and combined associations of cord blood mtDNA heteroplasmy and copy number with the risk of childhood overweight or obesity (OWO). Data were obtained from 952 children enrolled at birth and followed longitudinally in the Boston Birth Cohort. Body mass index (BMI) z scores were calculated using U.S. reference data, and OWO was defined as BMI ≥85th percentile for age and sex. Cord blood mtDNA heteroplasmy and copy number were assessed by targeted sequencing, with functional region heteroplasmy defined as heteroplasmic variants in coding regions and classified as inherited or de novo. Mixed-effects models were used to evaluate associations between mtDNA measures and repeated measures of child BMI and OWO. In sex-specific analyses, de novo functional region heteroplasmy was associated with higher BMI z score (β = 0.29, 95% CI: 0.01, 0.57) and increased risk of OWO (RR = 1.46, 95% CI: 1.07, 2.00) among girls, whereas no associations were observed overall. BMI associations were more evident in adolescent girls (aged 10-18 years). MtDNA copy number z score was negatively associated with BMI in children with overall or de novo functional region heteroplasmy but showed modest positive associations in those without specific heteroplasmy (p for interaction < 0.05). Cord blood mtDNA heteroplasmy and copy number interactively influence the risk of childhood OWO, with associations varying by sex and age. This is the first prospective study to jointly evaluate these mtDNA biomarkers, offering new insight into mitochondrial contributions to the developmental origins of OWO and a potential framework for early-life risk assessment.
To explore key informants' perspectives on how France has maintained a lower obesity prevalence than other high-income countries and the challenges that may limit France's current response to the obesity epidemic. Semi-structured interviews were conducted with 15 stakeholders based on their expertise and involvement in obesity clinical management, research, or policy in France. An inductive thematic analysis process was used to identify themes across the narrative data. Despite France's lower obesity prevalence, public health stakeholders perceive that obesity remains a growing public health concern, particularly among disadvantaged groups. Factors perceived as beneficial for obesity prevention in France included key nutrition policies such as the French National Nutrition and Health Program (PNNS), Nutri-Score (front of package labeling), physical activity prescription, and school meals, and cultural factors, namely the traditional French eating culture that encompasses structured, seated meals associated with sharing. However, factors that could prevent France from further reducing obesity rates included strong food industry lobbying, non-mandatory policies, and limited political will. Stakeholders believed that adherence to French eating culture, as well as several nutrition policies, has contributed to the relative success of France in mitigating the increase in obesity rates, at least in certain subgroups of the population. However, they suggest that there is still much progress to be made, given rising obesity rates driven by social disparities. Further coordination and strengthening of health-equity focused public health initiatives are needed to support efforts in obesity prevention in France.
Given the potential of organochlorine pesticides (OCPs) to disrupt metabolic health, we aimed to explore their association with obesity and to explore the potential bidirectional mediating relationships involving metabolic health indicators among 894 rural Chinese adults with prediabetes. A total of 894 individuals were included in this cross-sectional study. The associations of plasma OCPs on obesity and obese anthropometric measurements were assessed by generalized linear regression models for single exposure, and quantile g-computation (QGC) and LASSO regression for mixed exposure. The potential contributions of multiple health indicators to observed associations were assessed through mediation analysis. Exploratory bidirectional mediation analysis was employed to assess two potential pathways: (1) whether metabolic health indicators mediate the association between OCP exposure and obesity, and (2) whether obesity mediates the relationship between OCP exposure and metabolic health indicators. We discovered that β-Benzene hexachloride (β-BHC) and p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) were related to obesity for single exposure. QGC and LASSO demonstrated that OCPs were positively correlated with a higher likelihood of obesity for mixed exposure, with β-BHC being the primary contributor. Exploratory mediation analysis found that obesity and metabolic-related indicators play a bidirectional mediating role in the association with OCPs, mainly involving systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-Cholesterol (HDL-C), low-density lipoprotein-Cholesterol (LDL-C), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase/alanine aminotransferase (AST/ALT). In this cross-sectional study, we found that OCPs exposure may increase obesity risk both directly and by disrupting metabolism, while obesity itself can worsen OCP-related metabolic damage, revealing a bidirectional environment-body interaction.
Time-restricted eating (TRE) induces a metabolic shift in substrate utilization increasing lipolysis and ketogenesis. These metabolic changes raise the possibility of a differential effect on energy balance regulation following TRE-induced weight loss. The aim of this study is to evaluate the impact of TRE on energy balance homeostasis in individuals with overweight/obesity and type 2 diabetes (T2DM) who participated in a recently reported trial achieving substantial weight reduction (-3.86% body weight). In this randomized cross-over trial, 39 participants with overweight/obesity and T2DM were randomized to either 6 weeks of TRE (20 h fasting/4 h eating) or standard lifestyle, followed by 4-week washout and then the other dietary intervention for 6 weeks. At each study visit at baseline, 6-, 10-, and 16-week participants completed a 75 g oral glucose tolerance test (OGTT). We measured fasting and post-challenge responses of glucose, glucagon, GLP-1, ghrelin, leptin, and peptide YY. TRE-induced calorie deficit as participants self-reported ingested -384 ± 488 Kcal/day less during TRE as compared to the standard lifestyle period (P < 0.001) with no differences in macronutrient distribution. There were no differences in responses to OGTT induced by TRE as compared to standard lifestyle for glucagon (AUC0-120 min 0.04 ± 23.5, P = 0.99), GLP-1 (AUC0-120 min 1.6 ± 67.6, P = 0.98), ghrelin (AUC0-120 min 31.0 ± 32.4, P = 0.35), and peptide YY (AUC0-120 min -33.9 ± 65.6, P = 0.61). Importantly, TRE-induced weight loss promoted a significant decrease in both fasting leptin (-2445 ± 885 ng/mL, P = 0.009) and leptin response to OGTT (AUC0-120 min -12776 ± 3088, P < 0.001) as compared to standard lifestyle. In addition, a significant increase in fasting ghrelin (28 ± 11.3 pg/mL, P = 0.02) was observed post-TRE as compared to pre-intervention. These findings demonstrate that TRE does not prevent the physiologic compensatory changes associated with weight reduction in individuals with overweight/obesity and T2DM.
Amid rising global obesity rates and advances in weight-loss therapies, monitoring body composition and ectopic fat could refine trial design. We quantified weight-related changes in body composition and liver steatosis prior to widespread adoption of incretin treatments. Adults (N = 3070) from the UK Biobank with repeat abdominal MRI scans were included. Percent weight change from baseline was categorised: stable (0 ± 2%), mild change (2-5% weight gain/loss), moderate change (5-10% weight gain/loss), or large change (10-15% weight gain/loss). MRI data were processed automatically from two visits, spaced 2.7 years apart, to derive volumetric visceral (VAT), subcutaneous adipose tissue (SAT), total skeletal muscle volume (SM, or indexed SM), muscle fat infiltration (MFISM), and psoas muscle cross-sectional area (CSA) in the abdominal region. Liver fat content (LFC) was assessed using LiverMultiScan. Dual-energy x-ray absorptiometry (DXA) measurements were compared. Weight gain occurred in 28% of all subjects (N = 3070, age 63 years, male 49%, 13% with obesity, 43% with overweight). Moderate or large weight gain increased LFC, VAT, SAT, MFISM, and SM (all p < 0.001). Weight loss also occurred in 28%. Decreases were observed with moderate or large weight loss in LFC, VAT, SAT, SM, SMI, and psoas CSA (all p < 0.001). MFISM was reduced with large weight loss. For VAT and liver fat, prevalent type 2 diabetes exacerbated weight gain-related increases, and blood pressure medication attenuated the impact of weight change. For individuals with overweight or obesity, for every 5% drop in weight, there was 16% reduction in VAT, 11% in SAT, 24% in liver fat, 2.3% in MFISM, 1.5% in SM (or 1.4% in SMI) and 2.1% in psoas CSA. DXA changes in lean mass correlated weakly with changes in SM volume (rho 0.28-0.47). Using MRI, relative changes in body composition and liver steatosis resulting from weight loss can inform clinical trials, including placebo arm design and power estimations. Weight changes affect body composition and liver fat and can inform obesity trial design.
The correlation between fatty pancreas (FP) and metabolic-associated steatotic liver disease (MASLD), diabetes and other metabolic diseases is still controversial, and it is crucial to recognize the risk factors of FP to prevent its clinical complications. Retrospective collection of clinical, pathologic, and imaging data of people with obesity attending Qilu Hospital of Shandong University from January 1, 2020 to October 1, 2022. FP was diagnosed by non-enhanced computed tomography with the ratio of pancreas/spleen <0.7. Using binary logistics regression analysis to construct an FP prediction nomogram model, bootstrap repeated sampling internal validation and temporal external validation were used to test the predictive performance of the model. In this cohort, the average age of the participants was 32.2 years, and the average BMI was 41.3 Kg/m2. The prevalence of FP 23.3% (144/617). People with obesity with or without comorbid FP have partial differences in blood glucose, lipid. Independent factors for FP were body mass index (BMI) (OR = 1.97, 95% CI 1.29-3.01; P = 0.002), diastolic blood pressure (DBP) (OR = 1.55, 95% CI 1.03-2.33; P = 0.035), high-density lipoprotein (HDL) (OR = 1.67, 95% CI 1.11-2.52; P = 0.014), HbA1C (OR = 1.99, 95% CI 1.19-3.34; P = 0.009). This study constructed a nomogram containing these four indicators for FP, and receiver operating characteristic curve analysis indicated that the nomogram has moderate predictive performance. This study identified key risk factors and developed a validated prediction nomogram for FP in adults with obesity. This model may facilitate early identification of FP and the prevention of related metabolic disorders.
Obesity is a known cardiovascular risk factor, but the "obesity paradox" has been observed in patients with acute myocardial infarction (AMI), where obesity may be linked to better survival outcomes. The relationship between body mass index (BMI) and recurrent myocardial infarction, particularly with age-specific effects, remains unclear. This retrospective cohort study included 4023 AMI patients from a tertiary medical center (2015-2023). Patients were stratified by age: ≤60 years (n = 1277) and >60 years (n = 2746). Multivariable-adjusted Cox proportional hazards models were used to assess the association between BMI and recurrent myocardial infarction, adjusting for demographics, biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT)], imaging parameters [left ventricular ejection fraction (LVEF)], comorbidities, and treatment regimens. Curve-fitting models were also applied. The median follow-up time was 35 months (Q1-Q3 25-58). In the ≤60 years group, higher BMI was associated with a significantly lower risk of recurrent myocardial infarction [adjusted hazard ratio (HR) = 0.965, 95% confidence interval (CI) 0.936-0.994, P = 0.018]. In contrast, the >60 years group showed a trend toward higher risk (unadjusted HR = 1.032, 95% CI 1.012-1.053, P = 0.001), which lost statistical significance after adjustment (adjusted HR = 1.015, 95% CI 0.994-1.037, P = 0.151). Curve fitting revealed a negative linear correlation in the ≤60 years group and a positive relationship in the >60 years group. This study presents the first evidence of an age-dependent obesity paradox in AMI. In patients aged ≤60 years, higher BMI reduced recurrent myocardial infarction risk, whereas in those aged >60 years, the protective effect disappeared and reversed, indicating potential harm. These findings highlight the need for age-stratified secondary prevention strategies for AMI. Summary of Principal Study Outcomes.
Neuropeptide Y (NPY), a key orexigenic neurotransmitter, is widely expressed in the central nervous system, including in a distinct subpopulation of neurons within the central nucleus of the amygdala (CeA). While CeA NPY neurons contribute to energy regulation during chronic stress or high-fat diet exposure, the role of these neurons in modulating ingestive behaviour under standard conditions, particularly in response to caloric and non-caloric cues remains poorly understood. Using state-of-the-art chemogenetic techniques, we selectively activate NPY-expressing neurons in the CeA of NPYCre/+ transgenic mice, enabling precise control of their activity in freely behaving animals. Our experiments revealed that activation of these neurons significantly increased the consumption of both caloric and non-caloric palatable solutions, without affecting overall macronutrient preference. These findings indicate that CeA NPY neurons drive reward-related ingestive behaviour, promoting excess consumption beyond homoeostatic energy needs, regardless of the nutritional value of food. Importantly, this effect was observed independently of metabolic stress or dietary manipulation, suggesting that CeA NPY neurons engage a neural pathway that prioritizes food consumption based on reward value alone. This study provides novel insights into the neurobiological mechanisms underlying reward-driven consumption and identifies CeA NPY neurons as a key node in the neural circuitry mediating hedonic appetite. These findings have potential implications for understanding the pathophysiology of overeating and for developing targeted interventions for disorders characterized by dysregulated reward-based consumption.