International Journal of Obesity最新文献

Breast cancer has now become the most common malignant tumor and the leading cause of cancer deaths in women worldwide, and its pathogenesis has not yet been elucidated. Obesity is a risk factor for multiple cancers, and with the improvement of living standards and changes in dietary structure, obesity has become a major public health challenge in Asia, North America, Europe, and even worldwide. The study of obesity and breast cancer risk is a popular topic in epidemiological research. However, due to variations in obesity assessment criteria, conclusions regarding breast cancer risk in premenopausal versus postmenopausal women have been inconsistent. This review systematically reviews diverse diagnostic criteria for obesity from domestic and international studies, and thoroughly analyzes the differential associations between obesity and breast cancer risk in premenopausal and postmenopausal women, along with their potential molecular biological mechanisms. This paper further summarizes the clinical characteristics of breast cancer patients with obesity, including delayed diagnosis, poor pathological features, and unfavorable prognosis. At the mechanistic level, we integrate multidimensional evidence spanning obesity-related genes (e.g., fat mass and obesity associated genes (FTO)), adipokines (e.g., leptin (LEP), resistin, visfatin, adiponectin (ADPN)), estrogen metabolism, chronic inflammation, and tumor microenvironment remodeling (including cancer-associated adipocytes, extracellular matrix, and microbiota). Finally, this paper envisions the broad prospects of bariatric metabolic surgery in future adjuvant breast cancer treatment. By comprehensively employing lifestyle interventions, drug therapies, and bariatric metabolic surgery, we can provide patients with more comprehensive and personalized treatment plans to achieve better therapeutic outcomes and prognosis.

Background: This study aims to assess the impact of insulin resistance (IR) on gut microbiota (GM) composition, incretin responses, and metabolic outcomes following sleeve gastrectomy (SG) in people with severe obesity who do not have diabetes.

Methods: A prospective single-center study encompassed patients with severe obesity and normal glucose tolerance who underwent SG. Participants were stratified into two cohorts based on the magnitude of their insulin resistance state, as determined by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index: high-IR (Hi-IR; HOMA-IR > 95th percentile) and low-IR (Lo-IR; HOMA-IR <25th percentile). Body composition measurements, biochemical analyses, and microbiota assessments were performed before and 6 months post-surgery. Additionally, the responses to a standardized meal tolerance test (MTT) of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were evaluated.

Results: The study cohort consisted of 18 patients (9 with Hi-IR and 9 with Lo-IR), with a mean age of 48.8 ± 9.2 years and a mean body mass index (BMI) of 45.03 ± 4.82 kg/m². Six months post-surgery, the mean percentage of total weight loss (WL) was 26.5 ± 6%, with both groups exhibiting enhanced secretion of GLP-1 and GLP-2 following MTT. At baseline, participants exhibited distinct microbiota profiles; the Hi-IR group showed a higher relative abundance of Prevotella species, which are previously associated with adverse metabolic and inflammatory profiles. Post-surgery, both groups exhibited positive incretin responses and significant modifications in GM composition. Notably, Hi-IR people experienced more pronounced changes in microbial diversity, including increases in Akkermansia and Veillonella species and decreases in Prevotella species. Enhanced GLP-1 and GLP-2 responses were correlated with WL and metabolic improvement, particularly in the Lo-IR population.

Conclusions: These findings underscore the role of GM in metabolic changes and surgical outcomes after SG. Targeting gut microbiota may offer a promising avenue for improving obesity treatment strategies.

Background: Obesity-related hypertension (OH) is driven by endothelial dysfunction, chronic inflammation, and oxidative stress, yet effective targeted therapies are lacking. This study aims to investigate the mechanisms by which brown adipose tissue-derived exosomes (BAT-Exos) improve vascular endothelial function in OH via HuR protein delivery.

Methods: Rat models with OH and palmitic acid-treated endothelial cell injury models were established. BAT-Exos were compared with white adipose tissue-derived exosomes (WAT-Exos) for therapeutic efficacy. In vitro, primary endothelial cells isolated from rat aortas were treated with palmitic acid to induce injury, followed by pre-treatment with BAT-Exos or WAT-Exos. Inflammatory cytokines, adhesion molecules, oxidative stress markers, eNOS activity, and nitric oxide (NO) levels were measured.

Results: BAT-Exos exert superior therapeutic effects compared to WAT-Exos in both in vivo and in vitro models of OH. In rat model of high-fat-diet-induced OH, BAT-Exos improved metabolic profiles, lowered blood pressure, and alleviated vascular remodeling, while reducing inflammation and restoring eNOS activity. In vitro, BAT-Exos significantly mitigated palmitic acid-induced endothelial dysfunction by suppressing pro-inflammatory cytokines, adhesion molecules, and oxidative stress markers, while enhancing nitric oxide production.

Conclusion: These findings confirm HuR as a key therapeutic cargo. The BAT-Exo-HuR axis represents a novel intercellular signaling pathway that improves vascular function and may serve as a promising strategy for treating OH and related cardiovascular disorders.

Background: Postmenopausal women tend to experience significant changes in body composition, particularly abdominal adipose tissue (AAT) deposition patterns, which are hypothesized to be critical factors influencing future chronic disease risk. The level of protein intake to maintain or achieve a more favorable body composition for health in postmenopausal women is a central, largely unanswered question relating to the appropriateness of current dietary guideline recommendations for sufficient protein intake (set at 0.8 g/kg/day).

Objective: To estimate the hypothetical effect of a range of protein intake levels on 3-year mean changes in body composition measures in postmenopausal women.

Methods: We analyzed data from 3789 postmenopausal women aged 50-79 enrolled in the Women's Health Initiative (WHI) to emulate a 3-year target trial of adhering to increasing levels of protein intake: ≥0.8 g/kg/d, ≥1.0 g/kg/d, ≥1.2 g/kg/d, and ≥1.5 g/kg/d. All participants had repeated Dual X-Ray Absorptiometry (DXA) scans with derived abdominal visceral (VAT) and subcutaneous adipose tissue (SAT). The measured differences in average levels of VAT, SAT, and other body composition measures determined at end of follow-up were estimated with the parametric-g formula.

Results: Over 3 years, hypothetical interventions of increasing levels of dietary protein intake are estimated to have dose-dependent reductions in abdominal VAT, SAT, and overall body fat, and increases in lean soft tissue, with potential benefits observed at ≥1.2 g/kg/day and the greatest estimated benefit at ≥1.5 g/kg/day of dietary protein. Compared to no intervention, if all participants hypothetically adhered to a total daily protein intake of ≥1.5 g/kg/day over 3 years, they would be estimated to have lower levels of VAT (-13.1 cm², 95% Confidence Interval [CI] -18.9, -7.3), SAT (-25.3 cm², 95% CI -39.7, -11.0), total body fat % (-1.0%, 95% CI -1.7, -0.3), body weight (-2.5 kg, 95% CI -3.7, -1.2) and greater lean soft tissue % (0.9%, 95% CI 0.3, 1.6) over 3 years.

Conclusion: This hypothetical emulated intervention suggests that postmenopausal women who maintain a hypothetical total protein intake of at least 1.2 g/kg/day could experience beneficial changes in abdominal VAT, SAT, and overall body composition over three years, with even greater estimated benefits observed at an intake of 1.5 g/kg/day. These findings suggest that protein intake higher than guideline recommendations may better support healthier body composition and lower chronic disease risk in postmenopausal women.

The Physiology Of the WEight Reduced State (POWERS) study is a multi-center NIH-funded clinical trial designed to determine the physiological basis for variability in weight loss maintenance among adults with obesity following participation in a behavioral weight loss program. Two hundred and five healthy adults, aged 25-<60 years, with body mass index 30-<40 kg/m² complete up to four serial assessments (before weight loss; after ≥7% weight loss; and four and 12 months later). This report, one in a five-part series on the POWERS study design, provides the rationale for and description of behavioral measures. Standardized laboratory meals are used to measure energy intake and eating-related behaviors. Behavioral and neurocognitive factors related to eating (e.g., food-choice decision making, taste preferences, reward, self-control) are assessed via computer-based tasks and self-report questionnaires. Functional and structural neuroimaging augment the behavioral assessments by identifying underlying neural circuitry. Psychological factors related to weight regulation (e.g., self-monitoring, stigma, self-efficacy) are assessed via self-report questionnaires. Free-living physical activity and sleep are measured via accelerometry, polysomnography and self-report questionnaires. We will evaluate how changes, integrated values and patterns in these predictors and components of energy intake and energy expenditure contribute to individual variability in weight change during the 12 months following weight loss. We anticipate that extensive phenotyping using sophisticated eating behavior paradigms and assessments of critical components of energy expenditure before and after weight loss will lead to improved predictions of successful weight loss maintenance. This, in turn, will inform more effective treatments for long-term sustained weight loss.

Background: In Australia, the rising prevalence of metabolic syndrome (MetS) presents a significant public health challenge. However, research on geographic and ethnic disparities remains limited. This study aimed to investigate the prevalence and temporal trends of MetS by geographic remoteness and between Indigenous and non-Indigenous Australians.

Methods: We analysed data from 44,760 adults (aged ≥18 years) derived from the National Health Survey (2014-2015 and 2017-2018) and the National Aboriginal and Torres Strait Islander Health Survey (2012-2013 and 2018-2019). Weighted prevalence estimates of MetS were calculated overall and stratified by remoteness. The Average Annual Rate of Change (AARC) in MetS prevalence was computed to assess temporal trends.

Results: MetS prevalence varied notably by remoteness and ethnicity. In the most recent surveys, 7.1% (95% CI: 6.19-8.19) of Indigenous adults (2018-2019) and 4.6% (95% CI: 4.23-4.99) of non-Indigenous adults (2017-2018) had MetS. Prevalence was higher in remote areas for both groups. Among non-Indigenous adults, MetS declined across most regions but increased in remote areas from 4.5% to 7.1% (AARC: +15.77%), while among Indigenous adults it remained stable in remote areas but rose in major cities and regional settings. Central obesity and type 2 diabetes (T2D) were the most prominent contributors to MetS among Indigenous adults, whereas hypertension and high cholesterol were more prevalent among non-Indigenous adults in regional areas. Central obesity was the most common MetS risk factor, affecting 57.4% (95% CI: 55.14-59.63) of Indigenous and 40.9% (95% CI: 39.90-41.85) of non-Indigenous adults. High cholesterol was the least common risk factor among Indigenous adults (7.6% [95% CI: 6.58-8.67]), whereas elevated blood sugar was the least common among non-Indigenous adults (4.8% [95% CI: 4.44-5.21]).

Conclusions: Substantial disparities in MetS exist across Australia, disproportionately affecting Indigenous Australians and residents of remote areas. Culturally tailored, region-specific interventions targeting obesity are urgently needed through Local Health Districts and Aboriginal Community Controlled Health Organisations.

Objective: To evaluate the efficacy of a comprehensive cognitive intervention as an add-on to a standard behavioral weight-loss intervention (BWLI) in improving anthropometric measures in individuals with excess weight.

Participants: This randomized controlled trial included 148 participants (126 women; mean BMI = 31.62 kg/m²); 86.5% participants (n = 128) completed the study.

Methods: Participants were randomized into three groups: (1) Cognitive group (received four cognitive trainings: inhibitory control, approach-avoidance bias modification, implementation intentions, and episodic future thinking); (2) Sham group (received placebo cognitive interventions); and (3) Control group (no cognitive intervention). All three groups received BWLI. Cognitive trainings were delivered through four consecutive 90-min online group sessions. BMI, weight, percentage of weight loss (%WL), and waist-to-height ratio (WHtR) were assessed at baseline, post-treatment, and 3- and 6-month follow-ups. Mixed 3 (group) × 3 (time point) analysis were conducted to examine changes over time and between groups. Chi-squared test was used to explore group differences in reaching a clinically meaningful %WL.

Results: Significant group-by-time effects interactions were found for BMI (p = 0.009), weight (p = 0.003), %WL (p = 0.004) and WHtR (p = 0.041). Post hoc analyses showed greater reductions in all anthropometric measures in the Cognitive group compared to the Control group at post-intervention and at both follow-ups. Further, only the Cognitive group showed significant improvements over time. At 6-month follow-up, effect sizes were moderate in the Cognitive group, small in the Sham group, and negligible to small in the Control group. A higher proportion of participants in the Cognitive group achieved a clinically meaningful %WL.

Conclusions: A comprehensive cognitive training delivered as an add-on to BWLI improved anthropometric outcomes in individuals with excess weight, with sustained effects over 6 months.

Background/objectives: Reference data for bioelectrical impedance analysis (BIA) parameters remain limited in youth, making sarcopenia assessment challenging. This study aimed to establish BIA reference values and determine sarcopenia cutoff points and prevalence in youth.

Subjects/methods: This cross-sectional study analyzed 1451 youth aged 10-25 years who underwent BIA using data from a nationwide survey. Reference values for body composition were established using the least mean squares method, which estimates age-specific percentiles. Sarcopenia was defined using skeletal muscle mass index (SMI), fat-free mass-to-fat ratio (FFM-MFR), and appendicular skeletal muscle mass-to-fat ratio (ASM-MFR) with age- and sex-specific cutoff values.

Results: Muscle-related parameters, including fat-free mass, fat-free mass index, ASM, and SMI, increased during puberty in both sexes, with a more pronounced increase in males, followed by a plateau or gradual increase after adolescence. Fat-related parameters, including fat mass, fat mass index, and percentage body fat, decreased until age 14 years in males before increasing, whereas in females, they increased until adolescence and declined after early adulthood. The prevalence of sarcopenia was 2.05% in males and 1.04% in females based on SMI, 5.21% in males and 6.38% in females based on FFM-MFR, and 5.06% in males and 5.79% in females based on ASM-MFR.

Conclusions: This study established BIA-based body composition reference values for youth using nationally representative data, identified age- and sex-specific sarcopenia cutoff points and prevalence estimates, and highlighted age- and sex-specific differences. These findings provide a valuable resource for the early identification and management of sarcopenia in youth.

Background: Adipose lipolysis, a process involving the degradation of triglycerides and the release of fatty acids and glycerol, is an important biological event in lipid metabolism. Canagliflozin (Cana), an oral antidiabetic drug, regulates blood glucose by inhibiting sodium-glucose cotransporter 2 (SGLT2) in renal tubules and has also been shown to improve lipid metabolism in adipocytes. This study aims to determine whether Cana directly affects adipose lipolysis and to explore the underlying mechanistic pathways.

Method: Primary mature adipocytes and differentiated preadipocytes isolated from the epididymal fat pads of Sprague-Dawley rats were used as in vitro models. The effects of Cana on glycerol release and lipase activity were evaluated using ELISA and Western blot analyses.

Results: Cana treatment directly inhibited basal glycerol release and lipase activity in both primary adipocytes and topically administered adipose tissue, achieving a dose-dependent 35% to 65% suppression of lipolysis. This was associated with a 2.3-fold decrease in the level of HSL phosphorylated at the Ser660 site. Using differentiated adipocytes derived from the human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, we found that Cana significantly attenuated glycerol release (~32% to 53% reductions) induced by lipolysis. Moreover, Cana exerted antilipolytic effects in models of both acute (isoprenaline-induced) and chronic (tumor necrosis factor-α-induced) lipolysis. Mechanistically, the antilipolytic effect of Cana was mediated through activation of the PI3K/AKT pathway and reduction of cAMP production.

Conclusion: In conclusion, Cana regulates adipocyte lipolysis via an SGLT2-independent signaling pathway, which enhances our understanding of its role in modulating lipid metabolism.

Background: The combined and interactive effects of multiple lifestyle behaviours on obesity risk are not well understood. We used Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to examine how adherence to public health recommendations for five lifestyle behaviours affects BMI and obesity risk.

Methods: The sample included 139,540 men and 125,455 women from the UK Biobank. We categorized fruit and vegetable intake, physical activity, sleep duration and alcohol intake as binary variables (meeting vs. not meeting guidelines), and smoking status into three categories (previous, current, never). These categories were combined to form 48 unique strata, representing all possible combinations of the five behaviours. Linear and binary logistic MAIHDA models were used, with individuals nested within strata, and BMI and obesity status (obesity vs. normal weight) as outcomes. Three models were employed: Model 1 (null), Model 2 (with fixed effects for lifestyle behaviours), and Model 3 (with confounders and fixed effects). Variance Partition Coefficient (VPC), Proportional Change in Variance (PCV), and predicted BMI and obesity risk were estimated.

Results: For both sexes, strata with the lowest obesity risk were associated with meeting most recommendations, while strata with the highest risk were linked to meeting few. Logistic Model 1 VPCs revealed 7% of variance in obesity risk among males and 5% among females was explained by between-strata differences. In Model 3, VPCs attenuated to 0.5% among males and 0.1% among females, suggesting differences in obesity risk were largely additive effects. PCVs from Model 3 also indicated primarily additive rather than interactive effects. Results were similar for BMI in the linear models.

Conclusions: Using a novel statistical approach, this study shows that additive effects of multiple lifestyle behaviours predominantly explain differences in BMI and obesity risk. Meeting more public health lifestyle recommendations is important in mitigating obesity risk.