Obesity (Silver Spring, Md.)最新文献

Objective: The intestinal luminal pH profile varies from stomach to rectum and becomes disrupted in diseases. However, little is known about the pH dependence of incretin hormone secretion, with most in vitro studies having failed to consider this modulatory factor or having used nonphysiological buffer systems. Here, we report the extracellular pH (pHe) dependence of glucagon-like peptide-1 (GLP-1) exocytosis from L cells.

Methods: The pHe dependence of GLP-1 release from GLUTag cells and murine ex vivo primary gut cultures was detected by ELISA. GLP-1 release was measured over a range of pHe under a physiological (CO₂/HCO₃ ^-) buffering regime and in its absence (HEPES buffer). The relationship between intracellular pH (pHi) and pHe was mapped given that at least some component of pH sensitivity is likely to be intracellular.

Results: GLP-1 secretion from L cells was pHe-dependent and stimulated under alkaline conditions. In the absence of glucose or extracellular calcium, secretion remained at a pHe-insensitive baseline. pHi followed changes in pHe, but the relationship was offset to more alkaline levels in the absence of CO₂/HCO₃ ^- buffer and became shallower if [Cl^-] changes that normally accompany [HCO₃ ^-] changes were compensated iso-osmotically with gluconate.

Conclusions: GLP-1 secretion is sensitive to pHe and the buffer present. Exploiting this mechanism therapeutically may benefit patients with obesity.

Objective: The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D).

Methods: Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.0, 35.0, and 40.0 kg/m² in White adults.

Results: During a median follow-up of 13.8 years among 507,763 individuals, 5.2% developed T2D. In women, BMI cutoffs for an equivalent incidence rate of T2D as observed at 40.0 kg/m² in White adults were 31.6 kg/m² in Black, 29.2 kg/m² in British Chinese, 27.3 kg/m² in South Asian, 26.9 kg/m² in Native Chinese, and 25.1 kg/m² in Singapore Chinese adults. In men, the corresponding BMI cutoffs were 31.9 kg/m² in Black, 30.6 kg/m² in British Chinese, 29.0 kg/m² in South Asian, 29.6 kg/m² in Native Chinese, and 27.6 kg/m² in Singapore Chinese adults. The race and ethnicity order was consistent when equivalent BMI cutoffs were estimated for class I and II obesity.

Conclusions: Establishing a race- and ethnicity-tailored classification of the three classes of obesity is urgently needed.

Objective: The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins.

Methods: Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed.

Results: RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT.

Conclusions: The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.

Objective: Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity.

Methods: Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days' gestation (term = 180 days), fetal liver samples were collected (n = 6/sex/group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot.

Results: CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total GR expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only.

Conclusions: Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk.

Objective: The objective of this study was to study the recovery from, and incidence of, work-restricting musculoskeletal pain after bariatric surgery compared with usual obesity care.

Methods: Pain in different body regions was monitored using questionnaires in the nonrandomized, prospective, controlled Swedish Obese Subjects (SOS) study, which included 2007 participants treated with bariatric surgery and a matched control group of 2040 participants receiving usual obesity care at primary health care centers. Self-reported pain in the neck and shoulders, back, hips, knees, and ankles was captured from questionnaires administered at baseline and after 1, 2, 3, 4, 6, 8, 10, 15, and 20 years.

Results: Compared with matched controls, bariatric surgery was associated with better recovery from baseline work-restricting knee and ankle pain in both the short (1-4 years) and long term (up to 20 years), as well as from back and hip pain in the short term. In participants without pain at baseline, bariatric surgery was associated with a lower incidence of developing new pain in the knee and ankle in the short and long term.

Conclusions: Bariatric surgery was associated with better recovery from pain, primarily in weight-bearing joints, as well as with prevention of pain development in the knee and ankle compared with matched controls receiving usual obesity care.

Objective: Churches are frequently used to reach Black adults to effect weight loss. However, there has been no recent review, to our knowledge, inclusive of solely Black adults in church settings. We sought to comprehensively examine the methodological approaches and weight-loss outcomes of church-based weight-loss lifestyle interventions conducted among Black adults to provide insights on literature gaps and offer suggestions for future research.

Methods: Google Scholar, PubMed, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) were searched for trials conducted in churches that reported weight outcomes at any time point. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guided manuscript development.

Results: A total of 15 studies (N = 2285) from 2007 to 2023 met inclusion criteria, and 33% were high-quality randomized trials. The majority were pilot studies (60%) conducted in the Southern United States. Most reported significant postintervention weight loss. The follow-up time points varied from 2 to 12 months. Methodological approaches included the following: cultural adaptations (93%); theory-guided (93%); delivered by community health workers (80%); and delivered in person in a group format (100%). Only one study offered individual-level attention beyond texts/emails. Most participants were well-educated female individuals.

Conclusions: Weight-loss interventions among Black church settings effect statistically significant weight loss, albeit in a small way. Limitations include pilot studies and small samples. More rigorously designed studies are warranted.

Objective: Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans.

Methods: Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio.

Results: Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss.

Conclusions: These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.

Objective: We aimed to investigate the associations of changes in metabolic health across categories of body size phenotype with the risk of colorectal cancer in a community-based prospective cohort.

Methods: In the current study, a total of 70,987 participants were included. Changes in metabolic health across categories of body size phenotype were assessed between the health examination for the first time in the years 2006 through 2009 and a 2010/2011 health examination. A multivariate Cox proportional hazards model was used to assess the associations of changes in metabolic health across body size phenotype categories with risk of colorectal cancer.

Results: During the median follow-up time of 11.04 years, 428 (0.60%) participants developed colorectal cancer. Compared with metabolically healthy normal-weight (MHNW) participants who remained MH, the risk of colorectal cancer was increased by 144% (95% CI: 1.21-4.95) for participants with metabolically healthy obesity (MHO) who converted to a metabolically unhealthy (MU) phenotype. Participants who were MU at baseline were still at increased risk of colorectal cancer, regardless of obesity status.

Conclusions: The MHO phenotype was a dynamic status over time, and converting to MU during follow-up and being initially MU were associated with having an increased risk of colorectal cancer, regardless of degree of obesity and body size phenotype.

Objective: The objective of this study was to explore the acceptability to the public of receiving weight screening and the offer of support to lose weight from dental teams.

Methods: A cross-sectional survey was conducted with recruitment of adults from dental practices and community and hospital settings in England and the National Institute for Health and Care Research (NIHR) Be Part of Research initiative.

Results: A total of 3580 participants were recruited across 22 dental sites and the NIHR Be Part of Research initiative. Sixty percent (n = 2055/3430) of participants reported that they would be comfortable with their height and weight being measured at a dental appointment. Male participants and those of non-White race and ethnicity had significantly increased odds of accepting weight screening (odds ratio [OR]: 1.98, 95% CI: 1.66-2.36; OR: 2.07, 95% CI: 1.42-3.03). Fifty-seven percent (n = 1915/3375) of participants reported that it would be acceptable for their dental team to offer support to help with weight management. Male participants and those of non-White race and ethnicity had significantly increased odds of accepting support (OR: 1.79, 95% CI: 1.49-2.13; OR: 1.62, 95% CI: 1.11-2.37). The most accepted form of support was provision of information on local weight-management programs (n = 1989/2379, 83.6%).

Conclusions: The public is largely receptive to receiving weight screening and the offer of weight interventions from dental teams. Feasibility studies to test the implementation of lifestyle weight interventions in dental settings are required.

Objective: This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.

Methods: An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G).

Results: In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni-adjusted p < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin-like growth factor I and insulin, and KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life.

Conclusions: These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.