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Nature Communications Jun 2024Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the...
Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell G signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell G signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α-cell G-coupled A adenosine receptors. Studies with α-cell-specific Gα knockout mice showed that α-cell G also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched G-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.
Topics: Glucagon; Animals; Glucagon-Secreting Cells; Signal Transduction; Mice, Knockout; Mice; GTP-Binding Protein alpha Subunits, Gs; Adenosine; Receptor, Adenosine A2A; Male; Mice, Inbred C57BL; Islets of Langerhans
PubMed: 38879678
DOI: 10.1038/s41467-024-49537-x -
Scientific Reports Jun 2024To examine the influence of Body Mass Index (BMI) on laparoscopic gastrectomy (LG) short-term and long-term outcomes for gastric cancer. A retrospective analysis was...
To examine the influence of Body Mass Index (BMI) on laparoscopic gastrectomy (LG) short-term and long-term outcomes for gastric cancer. A retrospective analysis was conducted on gastric cancer patients undergoing LG at the Third Hospital of Nanchang City from January 2013 to January 2022. Based on WHO BMI standards, patients were categorized into normal weight, overweight, and obese groups. Factors such as operative time, intraoperative blood loss, postoperative complications, and overall survival were assessed. Across different BMI groups, it was found that an increase in BMI was associated with longer operative times (average times: 206.22 min for normal weight, 231.32 min for overweight, and 246.78 min for obese), with no significant differences noted in intraoperative blood loss, postoperative complications, or long-term survival among the groups. The impact of BMI on long-term survival following LG for gastric cancer was found to be insignificant, with no notable differences in survival outcome between different BMI groups. Although higher BMI is associated with increased operative time in LG for gastric cancer, it does not significantly affect intraoperative blood loss, postoperative complications, recovery, or long-term survival. LG is a feasible treatment choice for obese patients with gastric cancer.
Topics: Humans; Stomach Neoplasms; Gastrectomy; Body Mass Index; Male; Laparoscopy; Female; Middle Aged; Retrospective Studies; Aged; Treatment Outcome; Postoperative Complications; Operative Time; Obesity; Adult; Blood Loss, Surgical
PubMed: 38879651
DOI: 10.1038/s41598-024-64459-w -
Scientific Reports Jun 2024The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of...
The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12-1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01-1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15-10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.
Topics: Humans; Colorectal Neoplasms; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Life Style; Risk Factors; Smoking; Exercise; Genome-Wide Association Study; Alcohol Drinking; Male; Body Mass Index; Female; Obesity; Waist-Hip Ratio
PubMed: 38879601
DOI: 10.1038/s41598-024-64813-y -
Cardiovascular Diabetology Jun 2024There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG).
METHODS
In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications.
RESULTS
Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques.
CONCLUSION
In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient.
TRIAL REGISTRATION
Clinicaltrials.gov number, NCT03975478).
Topics: Humans; Male; Female; Gastric Bypass; Gastrectomy; Adult; Middle Aged; Cholesterol, LDL; Treatment Outcome; Obesity, Morbid; Time Factors; Biomarkers; Weight Loss; Remission Induction; Laparoscopy; Hypercholesterolemia; Sitosterols
PubMed: 38879559
DOI: 10.1186/s12933-024-02296-x -
BMC Research Notes Jun 2024Bariatric surgery induces a significant loss of both fat mass (FM) and fat-free mass (FFM). The proteoglycan receptor syndecan-4 (SDC4) plays a crucial role in adipose...
OBJECTIVE
Bariatric surgery induces a significant loss of both fat mass (FM) and fat-free mass (FFM). The proteoglycan receptor syndecan-4 (SDC4) plays a crucial role in adipose tissue and skeletal muscle functions. Thus, this study was performed (i) to assess plasma SDC4 levels after both Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) surgeries, and (ii) to explore potential associations with changes in body composition variables.
RESULTS
Twenty-six patients (17 females) with severe obesity underwent SG (n = 13) or RYGB (n = 13) and were followed up to 1 year (1Y). Body weight, FM, FFM, and SCD4 were measured at baseline (BL), and at week 11 (W11) and 1Y after surgery. Independently of procedure, there was a significant body weight loss at W11, with an average FM and FFM reduction of 13.7 ± 0.6 kg and 5.3 ± 0.5 kg, respectively. Participants continued to lose weight afterwards, with a total weigth loss of 38.2 ± 1.5 kg at 1Y. No associations were found at BL between SDC4 levels and any anthropometric variable; however, SDC4 levels were lower than BL at both W11 and 1Y, independently of type of surgery. Additionally, changes in SDC4 between BL and 1Y were positively correlated with weight and FFM loss during the same period.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04051190 on 09/08/2019.
Topics: Adult; Female; Humans; Male; Middle Aged; Adipose Tissue; Bariatric Surgery; Body Composition; Gastrectomy; Gastric Bypass; Obesity, Morbid; Syndecan-4; Weight Loss
PubMed: 38879520
DOI: 10.1186/s13104-024-06822-8 -
Journal of Health, Population, and... Jun 2024The COVID-19 lockdown significantly impacted dietary habits and body weights globally, particularly in Egypt, where 57.03% of the population resides in rural areas,...
BACKGROUND
The COVID-19 lockdown significantly impacted dietary habits and body weights globally, particularly in Egypt, where 57.03% of the population resides in rural areas, despite lack of information. The study examines the impact of COVID-19 lockdown on the weight changes of the rural Egyptian population through behavioral, physical, and dietary changes.
METHODS
A cross-sectional online survey using Microsoft Forms was distributed in Delta regions in Egypt. The questionnaire used a modified version of the validated 14- items PREDIMED MedDiet Adherence Screener (MEDAS). The first part of the questionnaire addressed sociodemographic variables whereas the second one included questions related to dietary, behavioral and weight changes of participants. These changes were statistically tested for significance in relation to BMI, gender, home living, current job and family history of obesity.
RESULTS
A total of 306 participated in the study (70% females, 13% obese, 95% living with family, 56% university students, and 36% with family history of obesity). Obese showed a significant increase in sweet intake whereas underweight and normal weight people displayed a significant decrease in eating desire. Both females and males showed significant increase in consumption of fruits and vegetables with significant decrease in soft drink. However, women showed a significant decrease in sport activity relative to men. Participants living with family showed an increase in sweet intake while those living alone explored an increase in meal frequency. Employers revealed a significant decrease in sport activities and people with family history of obesity reported more sleeping times than those without family history of obesity.
CONCLUSION
During Covid-19 quarantine, Egyptians' eating habits improved, but daily routines were disrupted. Raising awareness about obesity and providing guidance on maintaining activity, energy, and mood is crucial for future quarantine situations.
Topics: Humans; COVID-19; Male; Female; Egypt; Cross-Sectional Studies; Adult; Feeding Behavior; Rural Population; Obesity; Quarantine; Middle Aged; Retrospective Studies; SARS-CoV-2; Body Weight; Surveys and Questionnaires; Young Adult; Diet; Health Behavior; Body Mass Index
PubMed: 38879511
DOI: 10.1186/s41043-024-00558-8 -
Journal of the American Heart... Jun 2024
PubMed: 38879463
DOI: 10.1161/JAHA.124.035948 -
Advances in Nutrition (Bethesda, Md.) Jun 2024Despite the well-documented adverse outcomes associated with obesity during pregnancy, this condition remains a promising modifiable risk factor. (Review)
Review
A Systematic Review and Bayesian Network Meta-Analysis Comparing In-Person, Remote, and Blended Interventions in Physical Activity, Diet, Education, and Behavioral Modification on Gestational Weight Gain Among Overweight or Obese Pregnant Individuals.
BACKGROUND
Despite the well-documented adverse outcomes associated with obesity during pregnancy, this condition remains a promising modifiable risk factor.
OBJECTIVE
The aim of this study was to ascertain the most effective treatment modalities for gestational weight gain (GWG) in pregnant women classified as overweight or obese.
METHODS
A systematic search was conducted across four electronic databases: Embase, EBSCOhost, PubMed, and Web of Science. To assess the quality of evidence, the Confidence In Network Meta-Analysis (CINeMA) approach, grounded in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, was employed. A Bayesian network meta-analysis was conducted to synthesize the comparative effectiveness of treatment modalities based on GWG outcomes.
RESULTS
The analysis incorporated 60 RCTs, encompassing 16,615 participants. Modes of intervention administration were classified as remote (R: eHealth (e) and mHealth (m)), in-person (I), and a combination of both (I+R). The interventions comprised five categories: education (E), physical activity (PA), dietary (D), behavior modification (B), and combinations thereof. The quality of the evidence, as evaluated by CINeMA, ranged from very low to high. Compared to the control group, the I-D intervention (mean difference (MD) = -1.27, 95% CI [-2.23, -0.32]), I-PADB (MD = -0.60, 95% CI [-1.19, -0.00]), and in I-B (MD = -0.34, 95% CI [-0.57, -0.10]) interventions showed significant efficacy in reducing GWG.
CONCLUSIONS
Preliminary findings suggest that the I-D intervention is the most efficacious in managing GWG among pregnant women who are overweight or obese, followed by I-PADB and I-B+R-B(m) treatments. These conclusions are drawn from evidence of limited quality and directness, including insufficient data on PA components used in the interventions. Owing to the absence of robust, direct evidence delineating significant differences among various GWG management strategies, it is tentatively proposed that the I-D intervention is likely the most effective approach. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: International Prospective Register of Systematic Reviews, CRD42023473627 STATEMENT OF SIGNIFICANCE: This study presents new methods using systematic review and Bayesian meta-analysis combined with direct and indirect evidence, to evaluate effective interventions for managing gestational weight gain in overweight and obese pregnant women. This approach addresses prior gaps by assessing various intervention methods' effectiveness and administration processes; providing more comprehensive analyses for this specific group of pregnant women.
PubMed: 38879168
DOI: 10.1016/j.advnut.2024.100253 -
Journal of Advanced Research Jun 2024Metabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the...
INTRODUCTION
Metabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the modulation of antioxidative stress and inflammation in multiple pathological processes; however, its roles in metaflammation and the proinflammatory macrophage (M1)-like state in adipose tissue have not been determined.
OBJECTIVES
We hypothesize that SelenoM could effectively regulate metaflammation via the Hippo-YAP/TAZ-ROS signaling axis in obesity derived from a high-fat diet.
METHODS
Morphological changes in adipose tissue were examined by hematoxylin-eosin (H&E) staining and fluorescence microscopy. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the impact of SelenoM deficiency on blood glucose levels. RNA-Seq analysis, LC-MS analysis, Mass spectrometry analysis and western blotting were performed to detect the levels of genes and proteins related to glycolipid metabolism in adipose tissue.
RESULTS
Herein, we evaluated the inflammatory features and metabolic microenvironment of mice with SelenoM-deficient adipose tissues by multi-omics analyses. The deletion of SelenoM resulted in glycolipid metabolic disturbances and insulin resistance, thereby accelerating weight gain, adiposity, and hyperglycemia. Mice lacking SelenoM in white adipocytes developed severe adipocyte hypertrophy via impaired lipolysis. SelenoM deficiency aggravated the generation of ROS by reducing equivalents (NADPH and glutathione) in adipocytes, thereby promoting inflammatory cytokine production and the M1-proinflammatory reaction, which was related to a change in nuclear factor kappa-B (NF-κB) levels in macrophages. Mechanistically, SelenoM deficiency promoted metaflammation via Hippo-YAP/TAZ-ROS-mediated transcriptional regulation by targeting large tumor suppressor 2 (LATS2). Moreover, supplementation with N-acetyl cysteine (NAC) to reduce excessive oxidative stress partially rescued adipocyte inflammatory responses and macrophage M1 activation.
CONCLUSION
Our data indicate that SelenoM ameliorates metaflammation mainly via the Hippo-YAP/TAZ-ROS signaling axis in obesity. The identification of SelenoM as a key regulator of metaflammation presents opportunities for the development of novel therapeutic interventions targeting adipose tissue dysfunction in obesity.
PubMed: 38879122
DOI: 10.1016/j.jare.2024.06.005 -
Nitric Oxide : Biology and Chemistry Jun 2024Obesity is commonly linked with adipose tissue (AT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic...
Obesity is commonly linked with adipose tissue (AT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO-OA) preferentially accumulates in white adipose tissue (AT) and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO-OA for 48 days), both HFD-fed Nrf2 and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO-OA treatment, no distinction was observed between Nrf2 and ANKO in the HFD-fed mice as well as in the Nrf2 mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2 and ANKO compared to LFD-fed Nrf2 mice. Notably, NO-OA treatment improved glucose tolerance in HFD-fed Nrf2 but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.
PubMed: 38879114
DOI: 10.1016/j.niox.2024.06.002