Obesity最新文献

Objective

Vertical sleeve gastrectomy (VSG) promotes significant metabolic improvements, though the underlying molecular mechanisms are not fully understood. Emerging evidence suggests that small extracellular vesicles (sEVs) contribute to metabolic improvements post VSG, such as improved fatty liver disease or adipose tissue function; however, it is unclear how different organ-specific sEVs interact with various metabolic parameters. The objective of this study is to establish the role of organ-specific sEVs in the metabolic improvements post VSG.

Methods

Demographic and anthropometric data, metabolic parameters, and sEV samples were collected pre VSG and 3–6 months post VSG in youth with obesity. sEV RNA was sequenced for bioinformatics analyses.

Results

A significant reduction of the liver-enriched mRNA cargo in sEVs was observed post VSG, whereas adipose-enriched mRNA cargo showed no such reduction. Liver-enriched mRNA cargo correlated with BMI, leptin, and resistin 6 months post VSG. Analysis of delta values (post minus pre surgery) revealed that adipose-enriched mRNA cargo correlated with markers of liver damage, whereas liver-derived mRNA cargo correlated with branched-chain amino acids.

Conclusions

Following VSG, significant changes occur in the liver-enriched mRNA cargo of sEVs. Liver-derived sEVs appear to influence adipose metabolism, whereas adipose-derived sEVs are linked with liver function, suggesting dynamic intertissue cross talk that shapes systemic metabolic outcomes.

Objective

From October 18 to 20, 2022, the National Institutes of Health held a workshop to examine the state of the science concerning obesity interventions in adults to promote health equity. The workshop had three objectives: (1) convene experts from key institutions and the community to identify gaps in knowledge and opportunities to address obesity, (2) generate recommendations for obesity prevention and treatment to achieve health equity, and (3) identify challenges and needs to address obesity prevalence and disparities and develop a diverse workforce.

Methods

A three-day virtual convening.

Results

Several key themes emerged from the workshop discussions that describe directions to build on the currently limited amount of research on obesity, disparities, and equity. Key themes centered on the determinants of health, leveraging technology, clinical, community, commercial, and policy approaches. Community-engaged work, particularly in populations that have received little focus (e.g., sexual gender minorities, Asian communities), was also discussed.

Conclusions

Future research may be impactful when multilevel approaches are undertaken that leverage equity-minded tools and can be scaled up to meet community-informed population needs in a variety of settings. Funding priorities and workforce development will be critical to realizing health equity.

Objective

This secondary analysis was conducted to compare the magnitude of adaptive thermogenesis (AT) following hypocaloric low-carbohydrate (CHO) versus low-fat diets in African American (AA) women.

Methods

Sixty-nine AA women with obesity were randomized to low-CHO or low-fat hypocaloric diets for 10 weeks, followed by a 4-week weight stabilization period (all food provided). At baseline and Week 13, insulin sensitivity (S _I) was measured by intravenous glucose tolerance test, body composition by bioimpedance analysis, total energy expenditure (EE) (TEE) by doubly labeled water, and resting EE (REE) by indirect calorimetry.

Results

Forty women finished the intervention, with an average weight loss of 6.3 ± 3.9 kg and no differences between groups. AT was present at the level of REE (−75 ± 136 kcal/day, p < 0.003, n = 38), but not TEE (−80 ± 288 kcal/day, p = 0.086, n = 40) at Week 13. Women with low S _I on the low-fat diet showed greater AT at the level of TEE compared to those on the low-CHO diet (−202 ± 213 vs. 127 ± 239 kcal/day, respectively, p < 0.006).

Conclusions

AA women with low S _I on low-CHO diets do not experience AT, which can contribute to the superiority of this dietary approach in inducing weight and fat mass loss.

Trial Registration

ClinicalTrials.gov Identifier: NCT03499509 https://clinicaltrials.gov/study/NCT03499509

Objective

This study aimed to identify key childhood obesity correlates in Southern California by analyzing individual components from four social determinants of health (SDoH) indices and explore their interactions.

Methods

We utilized publicly available data from 330 cities across 10 counties, incorporating childhood obesity rates from the 2019 California Department of Education Physical Fitness Test (684,419 children, 40% Latino). Fifty-two individual SDoH were obtained from the Healthy Places Index, Social Vulnerability Index, CalEnviroScreen, and Child Opportunity Index (2015–2019). Weighted quantile sum regression and an interpretable machine-learning tool were used to identify which individual SDoH were significantly associated with childhood obesity.

Results

We identified a SDoH mixture associated with increased percentile of childhood obesity (β [95% CI]: 10.1 [8.1, 12.1]). Fourteen factors significantly contributed, with the top six being school poverty, minority status, asthma emergency room visits, public assistance rates, hazardous waste sites, and lead exposure from housing. We also found positive associations between Latino percentage and key correlates. Cities with high school poverty and low-income housing burdens had higher obesity rates.

Conclusions

This analysis moved beyond composite indices to examine specific SDoH observed alongside childhood obesity in Southern California, drawing attention to dimensions related to school, healthcare, social services, and environmental exposures.

Objective

SURMOUNT-MAINTAIN aims to evaluate the efficacy and safety of reducing the tirzepatide dose and/or continuing the maximum tolerated dose (MTD) versus placebo in maintaining body weight (BW) reduction achieved with tirzepatide MTD.

Methods

This Phase 3b, multicenter, randomized, parallel-arm, double-blinded, placebo-controlled, 52-week clinical trial is in progress comparing treatment with once weekly tirzepatide (5 mg and/or MTD of 15 mg or 10 mg) versus placebo in achieving BW reduction maintenance from the initial 60-week open-label weight-loss period on tirzepatide MTD, in adults with obesity (BMI ≥ 30 kg/m² or ≥ 27 kg/m² with ≥ 1 obesity-related comorbidity, excluding type 2 diabetes). The primary endpoint is percent maintenance of BW reduction achieved during the weight-loss period at Week 112 among those who reached a BW plateau (i.e., < 5% BW change) between Weeks 48 and 60.

Results

Participants are mostly female (65%) with a mean ± SD age of 47 ± 13 years, BW 114 ± 27 kg, BMI 40 ± 8 kg/m², and waist circumference 119 ± 18 cm.

Conclusions

The SURMOUNT-MAINTAIN trial will evaluate whether reducing or continuing the tirzepatide dose as a long-term treatment option may help maintain the reduced BW initially achieved with tirzepatide MTD versus switching to placebo. Combined, this study may provide additional evidence to help tailor patient-centered strategies for maintenance of BW reduction in adults living with obesity.

Trial Registration

ClinicalTrials.gov identifier: NCT06047548

Objective

In SURMOUNT-4, participants with obesity or overweight regained substantial weight after tirzepatide withdrawal, whereas continued treatment resulted in additional weight reduction. We evaluated the effect of continued tirzepatide treatment on health-related quality of life (HRQoL) in SURMOUNT-4.

Methods

Participants who achieved tirzepatide maximum tolerated dose (MTD; 10 or 15 mg; N = 670) during a 36-week (W) lead-in period were randomized (1:1) to continue receiving tirzepatide MTD or switch to placebo through W88. HRQoL was assessed using patient-reported outcomes (PROs: SF-36v2, IWQOL-Lite-CT, EQ-5D-5L). Post hoc analysis included changes in PROs by weight reduction categories and baseline Patient Global Impression of Status for physical activity response categories among tirzepatide-treated participants and by weight regain categories in the placebo group.

Results

Tirzepatide treatment was associated with improved PROs from W0 to W36, and these improvements were maintained from W36 to W88 with continued tirzepatide treatment versus placebo. Tirzepatide-treated participants with greater weight reduction and those with physical function limitations at baseline showed numerically greater improvements in PROs. Greater weight regain among participants who switched to placebo was associated with worsening of PROs.

Conclusions

In participants with overweight or obesity, continued tirzepatide treatment was associated with maintaining HRQoL improvement, while treatment withdrawal resulted in worsening of HRQoL.

Trial Registration: ClinicalTrials.gov identifier NCT04660643.

Objective

To investigate whether whole-body cryotherapy (WBC) enhances weight loss, brown adipose tissue (BAT) activation, and metabolic outcomes during obesity management.

Methods

Nineteen adults with obesity were assigned to a 12-month lifestyle-based obesity management intervention with 28 WBC sessions (−110°C, 3–4 min, ~2 × week) over the first 5 months (CRYO, n = 10) or the intervention without WBC (CON, n = 9). The primary outcome was weight loss (5 and 12 months). Secondary outcomes included BAT glucose uptake and whole-body energy expenditure during cold stimulation (5 months), clinical parameters, subcutaneous adipose tissue transcriptomics, and skeletal muscle proteomics (5 and 12 months).

Results

Weight loss in the CRYO group was 11.9% at 5 months and 9.9% at 12 months, compared to 11.5% and 8.0% in the CON group (p ≥ 0.54 for between-group differences). No significant between-group differences appeared in BAT glucose uptake, energy expenditure, adipose tissue transcriptomics, or skeletal muscle proteomics changes. However, at 5 months, the CRYO group showed greater reductions in fasting glucose (0.41 mmol/L, p = 0.026) and LDL cholesterol (0.44 mmol/L, p = 0.034).

Conclusions

WBC did not significantly enhance weight loss, activate BAT, or alter most metabolic responses during conventional obesity management. Further research is needed to confirm whether WBC benefits glucose and cholesterol metabolism.

Trial Registration: ClinicalTrials.gov: NCT01312090

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.