Obesity最新文献

Objective

Obesity is characterized by a proinflammatory condition contributing to poor outcomes, but its association with autoimmunity is inconclusive. To fill this gap in knowledge, we searched PubMed and Embase for studies analyzing the association between obesity and the prevalence and/or incidence of autoimmune diseases.

Methods

Adjusted odds ratios (OR) or hazard ratios (HR) with 95% CI relating to the prevalence or incidence of autoimmune diseases in people with BMI > 30, compared to BMI < 25, were pooled using generic inverse variance and fixed effect models. Of 1,311 records, 26 (8 cross-sectional and 18 longitudinal) studies were included in the meta-analysis.

Results

Obesity, compared with normal weight, was associated with increased prevalence of rheumatoid arthritis and psoriasis (OR = 1.11 [1.06, 1.16], p < 0.00001; OR = 1.35 [1.14, 1.59], p = 0.0004, respectively) and increased risk of developing rheumatoid arthritis (HR = 1.30 [1.15, 1.49], p < 0.0001), psoriasis (HR = 1.18 [1.16, 1.20], p < 0.00001), multiple sclerosis (HR = 1.49 [1.25, 1.77], p < 0.00001), and Crohn's/ulcerative colitis (HR = 1.35 [1.11, 1.65], p < 0.003). Obesity was also significantly associated with incidence of any autoimmune disease (HR = 1.41 [1.24, 1.62], p < 0.00001).

Conclusions

Although definitive conclusions are still precluded for the single diseases, overall evidence supports obesity as a risk factor for autoimmunity.

Objective

This post hoc analysis of SURMOUNT trials assessed the association of baseline physical function (PF) with obesity-related complications (ORCs), efficacy measures, and PF. The mechanism of tirzepatide-led improvements in PF was evaluated.

Methods

Outcomes were assessed among participants (SURMOUNT-1 = 2539; SURMOUNT-3 = 579; SURMOUNT-4 = 670) grouped by baseline quartiles (Q) of SF-36v2 PF scores within study (higher scores = better PF). Least-squares mean changes from baseline in efficacy measures and PF were estimated using ANCOVA. Pearson's correlation between weight reduction and improvement in PF was calculated.

Results

In SURMOUNT-1, participants with lower baseline PF had more ORCs. Tirzepatide-treated participants showed similar reductions in weight (kg; −20.1% to −22.8%), waist circumference (−17.2 to −20.2 cm), and BMI (−7.2 to −9.0 kg/m²) across quartiles. Participants with lower baseline PF reported greater improvements in PF with tirzepatide (Q1 = 12.5; Q4 = −0.8). Results were similar in SURMOUNT-3 and SURMOUNT-4. A weak to mild correlation was noted between weight reduction and improved PF; the strength of correlation decreased from Q1 to Q4.

Conclusions

Lower baseline PF was associated with a higher prevalence of ORCs. Patients taking tirzepatide experienced substantial weight loss, regardless of their baseline PF. Tirzepatide may improve PF through both weight loss-dependent and -independent mechanisms, especially in those with lower baseline PF.

Trial Registration

ClinicalTrials.gov identifiers: SURMOUNT-1, NCT04184622; SURMOUNT-3, NCT04657016; SURMOUNT-4, NCT04660643

Objective

This study aimed to investigate whether a single infusion of 5 mg zoledronic acid, given before bariatric surgery to prevent bone loss, could also hinder the loss of muscle mass, strength, and physical function.

Methods

In this double-blinded study, patients referred for bariatric surgery were randomized 1:1 to either intervention (INT: single dose zoledronic acid 5 mg) or placebo (CON). Assessments were conducted at baseline and 12 months postoperatively. The outcomes were body composition (DXA), muscle strength for knee extensor (KE) and knee flexor (KF), and physical function.

Results

Fifty-nine patients (age: 48.9 ± 6.3 years, BMI: 42.3 ± 5.3 kg/m²) were allocated to INT (n = 31) or CON (n = 28). At 12 months, no between-group differences were observed in body weight, fat mass, or lean body mass. Both groups experienced ~14% loss of lean body mass. No between-group differences were observed for absolute or relative muscle strength. Absolute strength declined by 11%–18%, while relative strength improved by 10%–22%. No between-group differences were found in physical function measures, all of which improved by 5%–18%.

Conclusions

A single infusion of 5 mg zoledronic acid did not prevent the loss of muscle mass or strength or improve physical function.

Trial Registration: ClinicalTrials.gov identifier: NCT04742010; EudraCT number: 2019-001650-26

Objective

Mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) is a crucial enzyme in the glycerophosphate shuttle, linking glycolysis, lipogenesis, and oxidative phosphorylation, making it a potential target for obesity treatment. Given the metabolic benefits of eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, we hypothesized that EPA modulates the GPD2-centered glycerophosphate shuttle to reduce adiposity, glucose intolerance, and inflammation while increasing energy expenditure.

Methods

Male and female GPD2 knockout (KO) and wild-type (WT) littermates were fed a high-fat diet (HF) without or with an 18 g EPA/kg (EPA) diet for 13 weeks. Body weight, glucose tolerance, and metabolic profiles were assessed, and blood and tissues were collected following euthanasia.

Results

Male GPD2 KO mice exhibited reduced adiposity and lower lipid accumulation in hepatic and adipose tissues compared to WT males. These effects were linked to lipid metabolism and beige fat activation. EPA supplementation reduced body weight and promoted glucose clearance in both WT and KO males, with enhanced hepatic lipid oxidation. However, GPD2 deficiency and EPA had minimal metabolic effects in females.

Conclusions

Our findings highlight potential mechanisms by which GPD2 combats obesity by mediating lipid metabolism. Our findings further demonstrate the sex-dependent nature of EPA's metabolic benefits, independent of GPD2 deficiency.

Objective

Despite successful weight loss, many individuals with obesity regain weight, yet cognitive factors in the weight loss state remain unclear. Here, we tested whether obesity induces deficits in cognitive flexibility, a core component of reinforcement learning (RL), after body weight normalizes.

Methods

Male and female C57BL/6J mice were exposed to high-fat diet-induced obesity followed by weight loss. Weight loss and control mice were tested on a modified probabilistic reversal learning (PRL) task to assess cognitive flexibility and a progressive-ratio (PR) task to evaluate motivation. RL modeling was applied to dissociate latent decision-making parameters.

Results

Post-weight-loss mice exhibited persistent impairments in PRL efficiency. Males showed reduced late-phase reversal efficiency (p < 0.001), while females showed early-phase inefficiency but later recovery (p < 0.05). RL modeling revealed reduced learning rates in both sexes, indicating impaired value updating despite intact motivation, as PR performance did not differ between groups. Across tasks, food intake remained unchanged, suggesting reduced efficiency reflected cognitive inflexibility rather than diminished appetite.

Conclusions

Weight loss after obesity produced sex-specific RL deficits. These findings dissociated motivational drive from cognitive flexibility and highlighted maladaptive decision-making as a feature of the weight loss state. This demonstrates the need for targeted interventions addressing post-weight-loss cognitive barriers.

Objective

This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods

The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with “no obesity,” “pre-clinical obesity,” and “clinical obesity.”

Results

Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m² [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m² [SD 3.5]), and 80.5% had clinical obesity (mean BMI 35.9 kg/m² [SD 4.3]). Participants with no/pre-clinical obesity had lower mean SF-12 mental component scores and greater baseline engagement with weight control strategies compared to those with clinical obesity. Participants with clinical obesity were older and, by definition, had a greater burden of cardiometabolic risk factors.

Conclusions

Among clinical trial participants eligible for obesity pharmacotherapy, 19.5% were classified as having no/pre-clinical obesity using the Lancet criteria. Applying the criteria was complicated in a well-resourced trial setting, which suggests potential challenges in implementing these guidelines in real-world practice.