Obesity最新文献

Objective

We examined the association between BMI change and risk of multimorbidity among women of reproductive age and estimated annual weight gain before and after diagnosis of chronic conditions.

Methods

Data were from 8895 women in the Australian Longitudinal Study on Women's Health who had no chronic conditions at baseline. BMI from Survey 1 (ages 18–23) and Survey 3 (ages 25–30) defined BMI change categories. Linear mixed models estimated annual weight gain from Survey 1 to Survey 9 (ages 43–49).

Results

Compared to stable normal BMI, stable obesity and increasing BMI were associated with a higher risk of incident multimorbidity (OR = 1.79 [95% CI: 1.11, 2.90] and 1.34 [1.10, 1.63]). Women who remained free of chronic conditions gained 0.50 kg (0.48, 0.52) annually. Women with one condition gained 0.54 kg (0.52, 0.56): 0.55 (0.53, 0.57) before and 0.54 (0.51, 0.57) after diagnosis. Those with multimorbidity gained 0.65 kg (0.63, 0.67): 0.75 kg (0.70, 0.80) before the first, 0.60 kg (0.56, 0.64) between the first and second, and 0.57 kg (0.53, 0.61) after the second condition.

Conclusions

Although weight gain declined after diagnosis, it remained higher than among women without conditions, underscoring the need for improved post-diagnosis weight management.

Objective

This study aimed to investigate the association between baseline insulin sensitivity (S_I) and changes in total lean mass (LM) and appendicular LM (ALM) during a diet-induced weight loss program with or without exercise.

Methods

We conducted a secondary data analysis from a controlled weight loss study in premenopausal women with overweight aged 21–41. Women were randomized into three groups: diet-only, diet plus aerobic exercise, or diet plus resistance exercise. Body composition was assessed using dual-absorptiometry X-ray and S_I using an intravenous glucose tolerance test. Multiple linear regression was used to determine if baseline S_I was predictive of changes in total LM and ALM.

Results

There were significant group-S_I interactions on changes in total LM (β = 0.474, p = 0.003, adjusted r ² = 0.371) and ALM (β = 0 0.462, p = 0.009, adjusted r ² = 0.231) after adjusting for covariates, indicating that greater baseline S_I was associated with less LM loss only in women who did not exercise.

Conclusions

Higher baseline S_I is associated with greater retention of LM when weight loss is induced with diet alone, but not when exercise (aerobic or resistance) is included. This reinforces the importance of including exercise in all weight loss interventions.

Trial Registration: ClinicalTrials.gov identifier: NCT00067873

Objective

This proof-of-concept study evaluated the impact of adding semaglutide as an adjuvant therapy to sleeve gastrectomy (SG) on weight loss and metabolic outcomes in obese mice.

Methods

C57Bl6/J male received for 12 weeks high-fat diet and 20% fructose-enriched water, then they were randomized to undergo SG or a Sham surgery and were subsequently treated with either semaglutide or a vehicle for 8 weeks. Mice were weighed weekly, and food intake, plasma glucose levels, and adipose tissue weights were measured.

Results

Both SG and semaglutide alone significantly reduced body weight compared with Sham surgery (−22.9%, p = 0.049 and −28.2%, p = 0.003, respectively). SG and semaglutide combination resulted in the greatest reduction (−30.0%, p = 0.003). Food intake was only significantly decreased in the semaglutide group. Although SG has no significant effect, semaglutide alone and in association with SG significantly decreased the plasma glucose concentration. The combination also led to a significant reduction in plasma cholesterol levels (−37.5% ± 4.8% vs. 5.6% ± 6.8%, p = 0.023). Liver steatosis was reduced in all treated groups.

Conclusions

Adding semaglutide to SG potentiates weight loss and metabolic benefits of surgery in obese mice, but no more than with semaglutide alone. These findings support further investigation of combined surgical and pharmacological approaches in obesity treatment.

Objective

This study quantifies the global burden of overweight and obesity, projects future trends, and examines associated health inequalities.

Methods

Overweight and obesity burden data were obtained from the NCD-RisC database. Trends from 1990 to 2022 were analyzed, and a Bayesian model was used to project changes for 2023–2040. Cross-national health inequalities were measured using the slope index of inequality (SII) and the relative concentration index (RCI).

Results

Globally, overweight prevalence rose from 17.50% in 1990 to 28.00% in 2022 (average annual percentage change [AAPC] = 1.48%) and is projected to reach 43.97% by 2040 (AAPC = 1.13%). Obesity prevalence grew from 6.44% to 16.06% (AAPC = 2.46%) and is projected to surge to 38.96% by 2040 (AAPC = 4.96%). The SII for overweight burden dropped from 33.74% in 1990 to 16.24% in 2022, and it is projected to reverse to −2.42% by 2040. For obesity (BMI, ≥ 30.0 kg/m²) and mild obesity (BMI, 30.0–34.9 kg/m²), the SII declined from 20.12% to 18.58% and from 14.22% to 10.02%, respectively, with further drops to 9.35% and −1.70% by 2040. From 1990 to 2040, the share of the global prevalence burden of overweight and obesity in countries with the lowest GDP per capita rose from 15% to 22% and from 6% to 26%, respectively. The relative gradient inequality, measured by RCI, also showed similar findings.

Conclusions

The global burden of overweight and obesity has significantly increased from 1990 to 2040. Health inequalities decreased from 1990 to 2022, with the burden mainly in higher-income countries. However, by 2040, the burden of overweight and mild obesity is projected to shift to lower-income countries, highlighting the need for targeted health policies and interventions.

Objective

This study investigates the regulatory role of p53 on Lgals3 expression and its impact on preadipocyte differentiation, fatty acid synthesis, and oxidation in obesity.

Methods

Bioinformatics analysis of six obesity-related microarray datasets and single-cell RNA sequencing (scRNA-seq) data identified Lgals3 as a key obesity-associated gene. A high-fat diet (HF) mouse model was established to evaluate obesity-related phenotypes, including body weight, hepatic Lgals3 expression, adipose tissue pathology, blood lipid profiles, and glucose tolerance. In vitro experiments using 3T3-L1 cells were conducted to assess adipocyte differentiation, fatty acid synthase (FAS) activity, and glucose uptake. The interaction between p53 and the Lgals3 promoter was analyzed via dual-luciferase reporter and chromatin immunoprecipitation assays. Key metabolic genes and proteins were quantified by RT-qPCR and Western blot.

Results

HF mice exhibited significant weight gain, elevated Lgals3 expression, and altered lipid profiles. In vitro, p53 was shown to transcriptionally repress Lgals3, thereby reducing adipocyte differentiation, FAS activity, and glucose uptake. In vivo, p53 overexpression led to downregulation of Lgals3 and improvement in obesity-related metabolic outcomes, whereas Lgals3 overexpression counteracted these effects.

Conclusions

p53 inhibits Lgals3 expression, suppressing adipocyte differentiation and improving obesity-related metabolic dysfunction, highlighting its potential as a therapeutic target in obesity management.

Objective

Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.

Methods

We generated mice simultaneously lacking the Opa1, Fgf21, and Gdf15 genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.

Results

Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined Fgf21 and Gdf15 deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.

Conclusions

FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.

Objective

This study aimed to describe the characteristics of American Board of Obesity Medicine (ABOM) physician diplomates over the last 8 years (2017–2024).

Methods

Using the ABOM database, we conducted a cross-sectional study of physicians who achieved initial ABOM certification between 2017 and 2024. Characteristics included demographics, primary medical specialty, years of obesity medicine experience, patient population, and practice setting. We conducted descriptive analyses and compared current characteristics with estimates extracted from the published ABOM 5-year report (2012–2016).

Results

Overall, 8640 physicians achieved initial ABOM certification between 2017 and 2024; 2068 achieved certification between 2012 and 2016. Between the 2012–2016 and 2017–2024 groups, notable differences were increases in physicians under age 40 years (22.7% vs. 47.6%, respectively), women (52.8% vs. 64.0%, respectively), and practicing obesity medicine for less than 2 years at initial certification (40.2% vs. 68.3%, respectively). The most common primary medical specialties were internal medicine (32.4%), family medicine (29.2%), and internal medicine subspecialties (14.2%).

Conclusions

We found that recent ABOM diplomates are likely entering the field earlier in their careers and with fewer years of obesity medicine experience than the initial group. Future investigation is needed to understand how ABOM and other obesity organizations can best support these physicians in their transition to obesity medicine clinical practice.

Objective

The melanocortin-4 receptor agonist setmelanotide has demonstrated effectiveness in phase 3 clinical trials for patients with monogenic obesity caused by biallelic variants in the leptin receptor (LEPR) and pro-opiomelanocortin (POMC), as well as for individuals with Bardet–Biedl syndrome (BBS). However, real-world evidence remains limited. This study evaluates the long-term effectiveness and safety of setmelanotide in patients who received treatment under a pre-marketing early-access authorization.

Methods

This ongoing prospective monocentric cohort includes 17 patients with obesity due to BBS (n = 11) or biallelic variants in LEPR (n = 4) or POMC (n = 2) who either started setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM-493-022 clinical trial. The average follow-up time was 14.4 months.

Results

Patients experienced a clinically significant weight reduction of 20% from their highest pre-treatment weight within the first year. Those previously treated in a clinical trial maintained their weight loss over time. Additionally, eating behavior improved, with significant reductions in hunger (−62%), food craving (−41%), and external eating evaluated by DEBQ. The overall safety profile was consistent with phase 3 trials data, without any new safety signals.

Conclusions

These findings confirm the drug's long-term clinical benefit and safety profile in a routine-care setting.

Objective

The doubly labeled water (DLW) intake-balance method estimates energy intake (EI) during weight loss using the time-weighted average of total daily energy expenditure (TDEE) and changes in body energy stores. Because TDEE declines rapidly during the early phase of weight loss, an early additional measurement is recommended. This study aimed to develop regression models that estimate time-weighted TDEE using fewer interim measurements and determine if EI accuracy is maintained during a 12-month weight loss intervention.

Methods

Data from a behavioral weight loss intervention (Dietary Caloric Restriction versus intermittent Fasting Trial, “DRIFT”) were used. TDEE, body weight, and body composition were measured at months 0, 1, 6, and 12. Regression models using only two or three time points were used to estimate time-weighted TDEE at months 6 and 12, respectively. Models were validated using bootstrap sampling, and time-weighted TDEE and percent caloric restriction (% CR) were compared to a reference approach.

Results

Models demonstrated strong predictive performance (R ² = 0.911–0.982). Limits of agreement with the reference model were 121.1–274.5 kcal/day for TDEE and 4.5%–10.3% for % CR, without significant bias.

Conclusions

Using a regression modeling approach, we demonstrate the DLW intake-balance method maintains accuracy during weight loss without early-phase TDEE measurements.

Trial Registration

ClinicalTrials.gov identifier: NCT03411356