Obesity最新文献

Objective

Glucagon-receptor (GCGR) agonism reguglates bile acid (BA) metabolism and promotes weight loss in diet-induced obese (DIO) mice. Thus, we hypothesized that BA signaling contributes to GCGR-stimulated weight loss.

Methods

To test this hypothesis, we utilized BA-binding resins (BARs; colesevelam [Colsv] and cholestyramine [Cstyr]) to prevent intestinal BA reuptake. DIO C57Bl/6J mice were administered the GCGR agonist IUB288 or vehicle, in the presence or absence of BARs.

Results

To our surprise, combined IUB288 and Colsv treatment reduced body weight and food intake compared to IUB288 or Colsv treatment groups in high fat diet (HFD)-fed mice. Moreover, acute IUB288 + Colsv treatment reduced fasting-stimulated HFD, but not chow, intake compared to IUB288 or Colsv treatments alone. We observed improved glucose homeostasis and reduced plasma cholesterol with combined IUB288 and Colsv, but not Colsv alone. Excitingly, liver steatosis was suppressed with IUB288 but not Colsv alone, and this benefit was further enhanced with combined treatment. Plasma BA profiles were regulated by both IUB288 and Colsv with concomitant modulation of liver and ileum BA regulatory mRNA expression. Similar findings were observed with the first-generation BAR Cstyr.

Conclusions

Together, these studies suggest that BARs enhance the antiobesity effect of GCGR agonism in DIO mice, representing a novel antiobesity strategy.

Objective

This study aimed to identify physical activity trajectories through pregnancy and examine associations with postpartum weight retention.

Methods

We included pregnancies from one health care system from 2009 to 2020. Data were collected from electronic health records and physical activity from self-report before pregnancy and during each trimester. High, medium, and low physical activity groups were identified using discrete trajectory analysis. The outcome was the percentage of postpartum weight retention in the first year after pregnancy, measured as postpartum BMI as a percentage of prepregnancy BMI. All postpartum BMI measures from 21 through 365 days were analyzed using mixed effects regression models using R version 4.4.1.

Results

Among 58,828 pregnancies, 54.7% were in Hispanic participants, 24.8% White, 10.3% Asian/Pacific Islander, 9.0% Black, and 1.3% other. Mean BMI after delivery was 105.2% ± 8.9% of prepregnancy BMI. Physical activity trajectories were high (3.4%), medium (64.9%), and low (31.6%). Compared with the low and medium physical activity trajectories, individuals in the high physical activity trajectory had greater odds of achieving prepregnancy BMI (OR: 1.314; 95% CI: 1.172–1.472 and OR: 1.285; 95% CI: 1.149–1.436, respectively).

Conclusions

Individuals with high physical activity from preconception through pregnancy have less weight retention at 360 days post partum than women with lower physical activity.

Objective

DNAJB3, a heat shock protein, plays a critical role in metabolic aberrations associated with obesity and type 2 diabetes (T2D). This study investigated how DNAJB3 deficiency exacerbates inflammation and glucose intolerance in diet-induced obese mice.

Methods

Male and female DNAJB3 knockout (KO) and wild-type (WT) mice were fed high-sucrose (17 kcal%) and high-fat (HF: 45 kcal%) or low-fat (LF: 10 kcal%) diets for 12 weeks. Body weight, food intake, glucose tolerance, and energy expenditure were assessed; blood, adipose, and liver tissues were collected for histological and gene expression analyses.

Results

HF-fed KO females exhibited higher body and fat mass and lower glucose clearance and energy expenditure, compared to other groups. Males showed a clear HF diet effect across both genotypes. Increased serum leptin, interleukin 6, and insulin levels were observed in HF-KO females, while HF-KO males showed higher leptin and resistin levels compared to other groups. Additionally, inflammatory and glucose transporter gene expression was altered by DNAJB3 deficiency in adipose tissues and the pancreas, highlighting the impaired glucose metabolism.

Conclusions

These findings suggest the importance of DNAJB3 in glucose and metabolic regulation, especially in females, and its potential use as a therapeutic target for obesity and T2D.

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