International Journal of Obesity最新文献

Background: Understanding how obesity impacts human mammary adipose tissue (MAT) biology is crucial for deciphering its role in mammary epithelium during both physiological and pathophysiological processes, including breast cancer. Hypertrophic mammary adipocytes and Crown-Like Structures are present in MAT of patients with obesity but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored.

Objective: We investigated the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of patients with obesity versus patients who are lean.

Methods: Tumor-free MAT were obtained from 96 women with (n = 43) or without (n = 53) obesity who underwent mastectomy for breast cancer risk reduction or treatment. Immune and non-immune cell infiltration were determined using flow cytometry. Bulk transcriptomic was used to characterize the phenotype of CD206+ macrophages whose infiltration is increased in patients with obesity. Conditioned-medium were prepared from MAT to characterize their secretome and dose adipokines and cytokines by ELISA assay. The extra-cellular matrix (ECM) deposition was evaluated by Masson trichrome staining on cross-stained sections, 3D imaging of red picrosirius-stained tissues and measure of hydroxyproline content.

Results: We observed an increase of CD206+/HLA-DR+ macrophages in the stromal vascular fraction of MAT from patients with obesity compared to patients who are lean. Other immune cell infiltration and endothelial or adipose progenitor cell numbers were similar between groups. Bulk transcriptomics on CD206+ macrophages revealed a significant decrease in ECM component expression and processing in obesity. In addition, no heightened secretion of pro-inflammatory cytokines, TGF-β1 or MCP-1 was observed in the samples from patients with obesity. ECM characterization revealed an absence of fibrosis, with MAT of patients with obesity showing even a slightly reduced collagen secretion and deposition compared with their lean counterparts.

Conclusions: Obesity is not associated with inflammation nor fibrosis in MAT, highlighting its unique behavior.

Introduction: Obesity is an independent risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) surgery. POAF in patients with severe obesity (body mass index [BMI] ≥ 35 kg/m²) is less studied. Whether waist circumference (WC) improves prediction of POAF independently of BMI among patients with severe obesity remains unknown.

Aim: To evaluate the risk of POAF, the role of WC in predicting POAF and postoperative complications after CABG surgery in severe obesity.

Methods: Our cohort included 7995 patients undergoing CABG surgery (2006-19). POAF risk was compared across BMI and WC categories. In patients with severe obesity, the association of an increase in WC with POAF risk was assessed.

Results: 763 (9.5%) patients had a BMI ≥ 35 kg/m². In this group, BMI was 38.5 ± 3.6 kg/m² and WC was 123.4 ± 10.8 cm. More patients with severe obesity developed POAF compared to patients with a normal BMI (37 vs. 29%, aRR: 1.52[95%CI 1.36-1.72], p < 0.01). Within each BMI category, the risk of POAF was higher per increasing tertile of WC (p < 0.05). Among patients with a BMI ≥ 35 kg/m², every 10 cm increment in WC was associated with an increased risk of POAF (aRR: 1.16[95%CI 1.08-1.24], p < 0.01). POAF in patients with severe obesity was associated with increased hospital length of stay.

Conclusions: Severe obesity increases the risk of POAF after CABG surgery. In this subgroup, elevated WC may provide additional prognostic value independently of BMI. Since POAF is associated with adverse long-term outcomes, abdominal obesity by measurement of WC should be assessed and targeted even in patient with severe obesity. Central Illustration Increasing waist circumference associated with increased atrial fibrillation risk post coronary artery bypass grafting. Bar graph of the unadjusted absolute risk and 95% confidence interval of postoperative atrial fibrillation for each tertile of waist circumference per body mass index category. Comparison of postoperative atrial fibrillation risk with chi-square test showing an increasing risk of postoperative atrial fibrillation related to increasing waist circumference within each body mass index category.

Abbreviations: BMI, body mass index; POAF, postoperative atrial fibrillation; WC, waist circumference.

Background/objectives: Circadian health plays an important role in overall well-being. The objective of this study was to examine whether potential indicators of circadian disruption, such as exhibiting a later chronotype or greater social jetlag, in preschool-age could predict dietary habits or BMI z-scores in an eight-year follow-up.

Subjects/methods: Our data included 210 children who participated in the DAGIS Survey in 2015-2016 (baseline, mean [SD] age: 4.69 [0.89] years) and DAGIS Next in 2023 (follow-up, age: 12.03 [0.90] years). Chronotype and social jetlag were calculated from baseline sleep measures assessed from 7-day actigraphy. Diet was assessed at follow-up with a Food Frequency Questionnaire, which evaluated the weekly consumption frequency of (1) fruits and vegetables and (2) sugary foods and drinks. BMI z-score based on Finnish growth references was calculated from height and weight measures from baseline and follow-up. Associations were analyzed with linear regression models.

Results: Follow-up BMI z-score was predicted by both preschool-aged chronotype (β-est: 0.22 [95% CI: 0.01, 0.42] p = 0.03) and social jetlag (β-est: 0.33 [95% CI: 0.02, 0.65], p = 0.04) after covariate adjustment. No associations were observed between preschool-aged chronotype or social jetlag and preadolescent fruit and vegetable or sugary food and drink consumption.

Conclusions: Having a later chronotype and greater social jetlag during preschool age predicted a higher preadolescent weight outcome. Obesity prevention initiatives should include efforts to reduce the risk of circadian disruption among young children, by accounting for chronotype and aiming to reduce social jetlag in interventions.

Background: Overwhelming evidence showed that obesity was associated with abnormal brain functional networks. However, the changes of structural covariance networks (SCNs) based on cortical thickness (CT) and cortical surface area (CSA) in obesity is still unclear.

Methods: In this study, 243 young adults with obesity and matched 243 lean individuals were enrolled from the Human Connectome Project Release S1200 dataset. All participants underwent magnetic resonance imaging scans following clinical and neuropsychological assessments. SCNs matrices were constructed by Brain Connectivity Toolbox based on both CT and CSA. Nonparametric permutation tests were adopted to examine group differences of these matrices.

Results: Young adults with obesity exhibited lower CSA of left entorhinal cortex, but higher CT of both left rostral anterior cingulate cortex and right superior parietal lobule, as well as lower CT of left temporal pole. While in terms of global network measures, there were no significant group differences; in terms of nodal network measures, young adults with obesity exhibited alterations in widespread brain regions including left posterior cingulate cortex, bilateral superior frontal gyrus, left entorhinal cortex and right insula.

Conclusions: Young adults with obesity exhibited abnormal nodal network measures in widespread brain regions involved in default mode network, central executive network and salience network. These findings indicate the adverse effects of obesity on young adults might be associated with the altered triple network.

This study aimed to clarify the trajectory of BMI alongside age-related changes in height and weight among Japanese adults. Data from annual health checkups between 2015 and 2020 by the Japan Health Insurance Association were retrospectively analyzed. A total of 4,777,891 men and 3,378,003 women (age 35-69 years) were stratified into 14 subgroups based on sex and 5-year age categories. We used linear mixed-effects model to estimate values for each outcome, with six-time points (2015-2020) as the independent variable. Mean BMI changes were positive across all subgroups, indicating a trend of increasing BMI (men, 0.02 to 0.14 kg/m²/year; women, 0.05 to 0.16 kg/m²/year). In younger subgroups, the changed were relatively large, with the weight transitions mirroring those of BMI. However, the mean changes were negative (men, -0.06 kg/year; women, -0.01 kg/year) in the oldest subgroups. Height reduction increased with age across subgroups (men, -0.14 to -0.03 cm/year; women, -0.18 to -0.01 cm/year). In conclusion, BMI tended to increase with age in both sexes across all age groups of Japanese adults. The increase in BMI appeared to be influenced by weight gain in young to middle age, whereas height reduction influenced increased BMI in older age groups.

Background: Evidence on the age-dependent association between adiposity and risk of dementia in the Chinese population is unclear. We aim to disentangle the association of mid- and late- life adiposity with subsequent dementia risk in Chinese adults and compare ageing trajectories of adiposity between those with/out dementia.

Methods: Dementia was ascertained based on cognitive batteries and the Activity of Daily Living Scale in the China Health and Retirement Longitudinal Study (CHARLS). Adiposity was measured by body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR). We estimated hazard ratio (HR) of adiposity for incident dementia by age groups (i.e. 50-64, and ≥65). Age trajectories of adiposity measures were fitted using a mixed-effect model in a case-control design. The interaction terms of age and dementia were included to examine the difference between cases and controls.

Results: Hazard ratios (HRs) for incident dementia in two age groups (50-64 and ≥65) were estimated in 13,355 participants. Raised mid-life BMI was associated with incident dementia (HR (95% CI): overweight 1.33 (1.03 to 1.73), obesity 1.63 (1.17 to 2.28)). Mid-life abdominal obesity was associated with incident dementia (WC 1.45 (1.15 to 1.84), WtHR 1.44 (1.08 to 1.94)), accounting for ≤24.2% of dementia cases. Among participants developing dementia, adiposity measures were higher in mid-life and declined faster with age, compared to those remaining dementia-free. Late-life adiposity was not associated with dementia risk.

Conclusion: Mid-life but not late-life adiposity was associated with dementia incidence in China. Accelerated weight loss in prodromal dementia is likely to explain the mixed evidence on adiposity and dementia risk in the Chinese population. Rapid decline in adiposity in later life may be an early sign. Reducing mid-life adiposity in the population may mitigate the future dementia burden.

Objectives: We investigated whether empirically derived childhood obesity phenotypes were differentially associated with risk of hypertension in young adulthood, and whether these associations differed by sex.

Methods: Data came from 11,404 participants in the Growing Up Today Study, a prospective cohort study in the US established in 1996. We used a childhood obesity phenotype variable that was previously empirically derived using latent class analysis. The childhood obesity phenotypes included an early puberty phenotype (females only), a mothers with obesity phenotype, a high weight concerns phenotype, and a mixed phenotype. Participants without overweight or obesity in childhood or adolescence were the reference group. We then used logistic regression models with generalized estimating equations to examine associations of childhood obesity phenotypes with incident hypertension between ages 20-35 years. All analyses were stratified by sex.

Results: Among females, participants in all of the empirically derived childhood obesity phenotypes were more likely than their peers without childhood overweight/obesity to develop hypertension in young adulthood (early puberty subtype odds ratio (OR) = 2.52; 95% confidence interval (CI) = 1.75, 3.62; mothers with obesity (MO) subtype OR = 2.98; 95% CI = 1.93, 4.59; high weight concerns (WC) subtype OR = 2.33; 95% CI = 1.65, 3.28; mixed subtype OR = 1.66; 95% CI = 1.25, 2.20). Among males, the childhood obesity phenotypes were associated with a higher risk of developing hypertension, although males in the MO (OR = 2.65; 95% CI = 1.82, 3.87) and WC phenotypes (OR = 3.52; 95% CI = 2.38, 5.20) had a greater risk of developing hypertension than the mixed subtype (OR = 1.51; 95% CI = 1.23, 1.86) (p = 0.004).

Conclusion: Risk for incident hypertension in young adulthood varied by childhood obesity phenotypes, as well as by biological sex. If replicated, these results may suggest that increased surveillance of specific childhood obesity phenotypes might help in targeting those at highest risk for hypertension.

Background: Human urine is highly favorable for ¹H NMR metabolomics analyses of obesity-related diseases, such as non-alcoholic fatty liver, type 2 diabetes, and hyperlipidemia (HL), due to its non-invasiveness and ease of large-scale collection. However, the wide range of intrinsic urine pH (5.5-8.5) results in inevitably chemical shift and signal intensity modulations in the ¹H NMR spectra. For patients where acidic urine pH is closely linked to obesity-related disease phenotypes, the pH-dependent modulations complicate the spectral analysis and deteriorate quantifications of urine metabolites.

Methods: We characterized human urine metabolites by NMR at intrinsic urine pH, across urine pH 4.5 to 9.5, to account for pH-dependent modulations. A pH-dependent chemical shift database for quantifiable urine metabolites was generated and integrated into a "pH intelligence" program developed for quantifications of pH-dependent modulations at various pH. The ¹H NMR spectra of urines collected from patients with Ob-HL and healthy controls were compared to uncover potential metabolic biomarkers of Ob-HL disease.

Results: Three urine metabolites were unveiled by pH-dependent NMR approach, i.e., TMAO, glycine, and pyruvic acid, with VIP score >1.0 and significant q-value < 0.05, that represent as potential biomarkers for discriminating Ob-HL from healthy controls. Further ROC-AUC analyses revealed that TMAO alone achieved the highest diagnostic accuracy (AUC 0.902), surpassed to that obtained by neutralizing pH approach (AUC 0.549) and enabled better recovering potential urine metabolites from the Ob-HL disease phenotypes.

Conclusions: We concluded that ¹H NMR-derived urine metabolite profile represents a snapshot that can reveal the physiological condition of humans in either a healthy or diseased state under intrinsic urine pH. We demonstrated a systematic analysis of pH-dependent modulations on the human urine metabolite signals and further developed software for quantification of urine metabolite profiles with high accuracy, enabling the uncovering of potential metabolite biomarkers in clinical diagnosis applications.