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Comparative Effects of Individual Glucagon-Like Peptide-1 Receptor Agonist-Based Medications on Direct Measurement of Body Composition Among Adults With Overweight or Obesity With or Without Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.
Diabetes Obes Metab
Nuttaya Wachiraphansakul, Thanawat Vongchaiudomchoke, Worapaka Manosroi +7 more
To compare the effects of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) on direct body composition among adults with overweight or obesity, with or without type 2 diabetes (T2D).
Beyond weight loss: multisystem benefits of obesity medications.
Lancet Diabetes Endocrinol
Mesut Savas, Susanne Kuckuck, Mariëtte R Boon +1 more
Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-topiramate, naltrexone-bupropion, glucagon-like peptide-1 (GLP-1) receptor agonists (eg, liraglutide, semaglutide, subcutaneously and orally), and newer GLP-1 receptor agonist-based agents (eg, tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). We evaluated the effects of obesity medications across major obesity-related conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea syndrome, polycystic ovary syndrome (recently named polyendocrine metabolic ovarian syndrome), osteoarthritis, muscle mass, depression, quality of life, and food cravings, along with binge-eating disorders, substance use disorders, and neurodegenerative diseases. Overall, GLP-1-based and multiagonist therapies show beneficial effects across these comorbid conditions. While many benefits of obesity medications are mediated by weight loss, accumulating evidence indicates important weight loss-independent effects, particularly with GLP-1 receptor agonist-based therapies. A broader understanding of these pleiotropic effects is essential to inform personalised obesity management and optimise long-term clinical outcomes.
Molecular Imaging of Butyrylcholinesterase Associated with Amyloid-β Plaques Distinguishes 5XFAD from Wild-Type Mice: A Proof-of-Concept.
Mol Imaging Biol
G Andrew Reid, Drew R DeBay, Ian R Macdonald +3 more
Diagnosis of Alzheimer's disease (AD) requires symptoms of dementia and accumulation of amyloid-β (Aβ) and tau in the brain. Molecular imaging of Aβ or tau in AD, though informative, is complicated by the finding that similar changes are found in brains of ~ 30% of cognitively normal older individuals. Butyrylcholinesterase (BChE), normally present in low levels in the cerebral cortex, is found in high levels associated with Aβ plaques in AD. When associated with plaques, the biochemical properties of BChE are altered. The aim of the present study was to determine if the BChE ligand, [18F]1-methyl-4-piperidinyl p-fluorobenzoate ([18F]BMP), can image BChE-associated plaques in the 5XFAD mouse model of AD and distinguish it from its wild-type (WT) counterpart.
Dynamic degradation and glycoform heterogeneity of NT-proBNP in serum: Implications for biomarker quantification.
Int J Biol Macromol
Junyi Wu, Xueting Ma, Yajing Dong +4 more
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a widely used biomarker for heart failure, yet its circulating molecular heterogeneity and susceptibility to ex vivo proteolysis complicate accurate and traceable quantification. In this study, we systematically investigated the degradation behavior of NT-proBNP in human serum and identified kinetically stable endogenous glycoforms using immunoaffinity enrichment coupled with MALDI-TOF mass spectrometry. Non-glycosylated recombinant NT-proBNP spiked into serum underwent rapid proteolytic processing, dominated by stepwise C-terminal truncation, with extensive fragmentation observed within hours even at 4 °C. Protease inhibition experiments performed under accelerated incubation conditions (37 °C, up to 48 h) confirmed that these changes were enzyme-driven. Against this dynamic background, two NT-proBNP-related peaks at m/z 9084 and 9517 remained qualitatively detectable throughout the entire incubation series, whereas labile non-glycosylated forms showed rapid attenuation. These peaks were reproducibly detected in the small NT-proBNP-positive sample set and were not detected in the small NT-proBNP-negative comparison set, supporting preliminary analytical specificity in this pilot dataset. Mass-balance modeling suggested that both species may correspond to proteolytically processed NT-proBNP backbones carrying clustered mucin-type O-glycosylation involving GalNAc, hexose, and sialic acid residues; these assignments should be regarded as putative compositions requiring orthogonal structural validation. Together, these results suggest that O-glycosylation may contribute to the qualitative persistence of specific NT-proBNP-related species in serum. The m/z 9084 and 9517 peaks should therefore be regarded as candidate, analytically persistent signals detected under the present 15F11-based immunoenrichment and MALDI-TOF MS workflow. Their potential use as robust analytical targets or anchors remains a hypothesis that will require orthogonal structural confirmation, quantitative validation, and evaluation in larger cohorts.
GIP in Cardiovascular and Kidney Disease: From Physiology to Pharmacology.
Diabetes Obes Metab
Michelantonio De Fano, Line L Haurum, Christine R Schwarz +2 more
To provide a comprehensive overview of the cardiovascular and renal effects of glucose-dependent insulinotropic polypeptide (GIP) by integrating its physiological role with recent human trial data on tirzepatide, the first dual GIP and glucagon-like peptide-1 (GLP-1) receptor agonist.
Zein Scaffold Preparation for Cultivated Meat.
J Biomed Mater Res A
Edward B Gordon, Amin Nikkhah, Sabrina Madiedo-Podvrsan +2 more
Cellular agriculture represents the intersection of biomaterials and cell science aimed at achieving high-quality, protein-rich, sustainable products. Developing cultivated meat products that address environmental and societal challenges requires the use of natural materials that support the replication of the characteristics of traditional meats while supporting cell growth in a scalable, low environmental impact process. Here, we utilize porogen leaching to form porous zein scaffolds that provide mechanical properties (Young's Modulus of 294 ± 102 kPa) and composition (75%-80% water and 20%-25% protein and cells) mimicking commercially available meat (e.g., rump roast), while supporting the growth of immortalized bovine satellite muscle cells. Over 2 weeks, cells showed significant growth and surface coverage even after initial low attachment. Enzyme-based food softening methods were used to reduce the mechanical properties of the scaffolds to replicate the consumer post purchasing process of tenderizing meat. The process developed was analyzed by life cycle assessment (LCA). The LCA results indicated that deionized water used for leaching the porogen was the primary contributor to environmental impact (e.g., global warming and water consumption), highlighting that scaffold environmental sustainability is influenced not only by feedstock selection but also by processing decisions. The zein scaffolds demonstrated promising mechanical, chemical, and cell supportive characteristics for cellular agriculture goals. Future research should focus on zein processing and sensory analyses to ensure meat-like outcomes in the final products, as well as sustainable design of scale up processes.
Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK Signaling Pathway.
Drug Des Devel Ther
Zhen Zhang, Delong Niu, Wenjie Qiu +3 more
Type 2 diabetes mellitus (T2DM) is a major risk factor for periodontitis, often leading to exacerbated alveolar bone loss. Ferroptosis, an iron-dependent regulated cell death pathway, contributes to osteoblast dysfunction under diabetic conditions. The non-canonical Wnt5a/Ror2 pathway is pivotal in inflammation and bone metabolism. Semaglutide, a long-acting GLP-1 receptor agonist, may modulate this pathway and protect osteoblasts from ferroptosis, however, its role in diabetic periodontitis remains unclear.
Lifestyle First and Lifestyle Always, Does Not Mean Lifestyle Only: Reimagining Cardiometabolic Care in the Era of GLP-1 Receptor Agonists.
Am J Lifestyle Med
Elizabeth Joy, Jonathan Bonnet
The rapid uptake of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and tirzepatide, has transformed the management of obesity, diabetes, and cardiometabolic disease, producing substantial weight loss, improved glycemic control, and reduced cardiovascular and renal risk. This article advances a guiding principle for contemporary care: "lifestyle first and lifestyle always, but not lifestyle only." While GLP-1 RAs have reshaped clinical practice and reinforced recognition of obesity as a biologically mediated disease, pharmacotherapy alone cannot resolve the complex behavioral, physiologic, and social drivers of cardiometabolic risk. Discontinuation of GLP-1 RAs without structured lifestyle support commonly results in weight regain, and medication does not address sarcopenia, physical deconditioning, sleep, stress, psychosocial determinants, or social connection. Lifestyle behaviors, high-quality nutrition, regular physical activity including resistance training, restorative sleep, stress management, social connectedness, and a sense of purpose, constitute the physiological and behavioral foundation for durable health gains. GLP-1 RAs are therefore positioned not as substitutes for lifestyle change, but as catalysts that create metabolic and psychological conditions that are favorable to adopting and sustaining healthy behaviors. Integrated, interprofessional models that combine pharmacologic and lifestyle strategies, supported by policy and systems change, are proposed as the emerging standard for long-term cardiometabolic health.
After the Prescription: The Clinical Support Gap in Telehealth-Based GLP-1 Care.
J Med Internet Res
Anna Zucker
GLP-1 medications offer promise for obesity management and are increasingly accessible via digital platforms. In this News and Perspectives article, JMIR Correspondent Anna Zucker reports on the gap in clinical support that could undermine their potential benefits.
Differential Biliary Adverse Event Signals Among Glp-1 Receptor Agonists: A FAERS Disproportionality Analysis.
Dig Dis Sci
Huda Alvina, Chidera N Jaffar, Abdelkader Onwuzo +2 more
Biliary adverse events (AEs) have been reported with glucagon-like peptide-1 receptor agonists (GLP-1RAs), but within-class differences remain unclear.
Evaluation of the safety profile of glucagon-like peptide-1 receptor agonists: a focus on thyroid cancer-related adverse events by using the European pharmacovigilance database.
Pharmacol Rep
Antonietta Anatriello, Valerio Liguori, Ciro Pentella +6 more
The therapeutic landscape for the treatment of type 2 diabetes mellitus (T2DM) has greatly evolved with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, concerns regarding their potential association with thyroid cancer have emerged. The aim of this study is to analyze individual case safety reports (ICSRs) involving GLP-1 RAs, focusing on thyroid cancer-related adverse events (AEs) using the European pharmacovigilance database.
Mitophagy in kidney and lung epithelial cells: molecular mechanisms, crosstalk, and therapeutic interventions.
Front Physiol
Xiaoxi Zhou, Jing Sun, Lining Miao +1 more
Mitophagy is a central component of mitochondrial quality control in both renal tubular and alveolar epithelial cells, where mitochondrial homeostasis is essential for barrier integrity, energy supply, and stress adaptation. Increasing evidence indicates that mitophagy is highly context-dependent across kidney and lung diseases: insufficient mitochondrial clearance is commonly linked to persistent mitochondrial dysfunction, epithelial senescence, and fibrotic remodeling, whereas dysregulated or excessive mitophagy may aggravate epithelial vulnerability under severe inflammatory or infectious stress. In this review, we summarize the molecular regulation of epithelial mitophagy, including PINK1/Parkin-dependent and receptor-mediated pathways, and examine its divergent roles in acute and chronic injury states in the kidney and lung. We further discuss a proposed mitophagy-centered framework for kidney-lung crosstalk. Current evidence is strongest for kidney-to-lung communication, particularly through circulating mitochondrial damage-associated molecular patterns and inflammatory mediators after acute kidney injury, whereas lung-to-kidney links remain supported mainly by organ-level inflammatory, hypoxemic, and hemodynamic mechanisms rather than direct evidence of pulmonary epithelial mitophagy-driven renal injury. Overall, the available literature supports mitophagy as an important mechanistic interface in epithelial injury, but not yet as a fully validated bidirectional epithelial axis. Future therapeutic strategies should therefore aim to restore mitophagy homeostasis in a disease- and stage-specific manner rather than uniformly enhancing or suppressing mitochondrial clearance.
EXPRESS: Oscillating Hypercapnia Induces Neural Abundant Protein Efflux and Potential Depletion in Health and Chronic Traumatic Brain Injury.
J Cereb Blood Flow Metab
Andrew Mayer, Tracey V Wick, Upasana Nathaniel +11 more
Emerging preclinical and clinical evidence suggests that low frequency hemodynamic oscillations drive CSF flow, which in turn mediates glymphatic clearance. The current study investigated whether CO2-induced low frequency hemodynamic oscillations during magnetic resonance imaging would increase clearance of proteins (glial fibrillary acidic protein, neurofilament light chain, ptau217 and brain-derived tau) from brain to blood, and temporarily improve cognitive performance in individuals with chronic traumatic brain injury (TBI) and age/sex-matched healthy controls. Results indicated that cerebrovascular reactivity, normalized CSF volume, and predicted brain age significantly differed between chronic TBI and controls, while bulk CSF flow differed only at trend levels. Multiple protein concentrations were significantly increased at ~45 minutes post-hypercapnia, decreased at ~90 minutes, and returned to pre-hypercapnia levels by ~150 minutes. Protein efflux was more strongly associated with total CSF volume and total white matter volume rather than cerebrovascular reactivity or bulk CSF flow. Both groups exhibited reduced cognitive interference post-hypercapnia, and hypercapnia associated symptoms quickly returned to baseline levels. In conclusion, hypercapnia temporarily increases clearance of multiple neural abundant proteins into blood, and this effect is moderated by atrophy. Current results suggest that hypercapnia may therapeutically combat pathological protein aggregation post-trauma, and prophylactically during normal aging.
Reduced plasma APJ levels and APLNR G212A polymorphism in Syrian patients with coronary artery disease.
Curr Med Res Opin
Maisaa Hassan Abd-Alkareem, Hussam Eddin Mohammed Shibli, Faizeh Ali Alquobaili
Coronary artery disease (CAD) remains a leading global cause of mortality. The apelin/apelin receptor (APJ) system has emerged as a novel pathway implicated in cardiovascular regulation and disease progression. This pioneering case-control study, the first conducted in a Syrian population, investigated the association of the apelin receptor G212A polymorphism and plasma APJ levels with CAD susceptibility.
Targeting Gut Microbiota by DPP-4 Inhibitors in Obesity: Mechanistic Insights and Therapeutic Implications.
Curr Nutr Rep
Mansour Alanazi, Hayder M Al-Kuraishy, Ahmed A Mohamed +4 more
Obesity is a complex metabolic disorder driven by factors such as chronic inflammation, insulin resistance, and significant alterations in the gut microbiota. Dipeptidyl peptidase-4 (DPP-4), an enzyme primarily known for inactivating incretin hormones like glucagon-like peptide-1 (GLP-1), is now recognized as a critical link between metabolic dysfunction and gut microbiome dysbiosis. This review aims to examine the mechanistic role of DPP-4 and its inhibitors in obesity, specifically focusing on how they modulate the gut microbiome to influence host energy balance and metabolic health.
[Advances in the role of adrenal microenvironment in maintaining homeostasis under inflammatory stress].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
Juan He, Lin Huang
Sepsis is one of the major diseases threatening human health. Under inflammatory stress, the rapid activation of glucocorticoids (GCs) and catecholamines (CAs) in the adrenal gland is crucial for maintaining the body's homeostasis. During severe inflammation, impairment of the hypothalamic-pituitary-adrenal (HPA) axis leads to suppressed secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACHT). However, studies reveal that the systemic glucocorticoid levels can remain normal or even elevated, suggesting a transition in the stress response mechanism from the central, pituitary-dependent regulatory system to local, pituitary-independent regulatory mechanisms. Among the various potential mechanisms, activation of the local adrenal microenvironment plays a significant role. In this microenvironment, interactions between adrenal cortical cells, medullary cells, vascular endothelial cells, and various immune cells contribute to the sustained production of GCs, which is pivotal in maintaining the internal homeostasis. This review focuses on the role of the local adrenal microenvironment in regulating the secretion of GCs and CAs, key hormones for maintaining homeostasis under inflammatory stress, with the aim of providing new insights into the etiology and pathogenesis of adrenal diseases.
Prognostic Value of Preoperative Left Ventricular End-Diastolic Dimension in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation With the Venus-A Valve.
Echocardiography
Baiqiang Mei, Zhaoyan Xu, Jian Li +9 more
Severe aortic stenosis (AS) leads to chronic pressure overload of the left ventricle (LV). We explored the prognostic value of preoperative left ventricular end-diastolic dimension (LVEDD) dilation in patients with severe AS.
Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury.
Sci Rep
Alperen Kutay Yıldırım, Hüseyin Demirtaş, Abdullah Özer +1 more
Ischemia-reperfusion (I/R) injury remains a major complication in peripheral arterial disease, characterized by oxidative stress, inflammation, and apoptosis. Body Protection Compound-157 (BPC 157), a stable gastric pentadecapeptide, has demonstrated cytoprotective properties in multiple tissues. This study aimed to evaluate the protective effects of BPC 157 in a rat model of lower limb I/R injury. Twenty-four male Wistar albino rats were randomized into four groups (n = 6): SHAM, B (BPC 157 only), IR (I/R), and IRB (I/R + BPC 157). I/R was induced by abdominal aortic clamping for 45 min followed by 2 h of reperfusion. BPC 157 (20 µg/kg, intraperitoneal) was administered at the 45th minute of ischemia in B and IRB groups. Biochemical markers (MDA, SOD, TAS, TOS) were measured in serum. Gene expression of Il-6, Hif-1α, p53, Bcl-2, Bax, and Casp3 was assessed by qRT-PCR, while immunohistochemistry evaluated VEGF, eNOS, IL-6, and Caspase-3 expression. Histopathological changes were scored with hematoxylin-eosin and Masson's trichrome staining. I/R significantly increased MDA, TOS, p53, Bax, Casp3, Hif-1α, Il-6, and histopathological injury scores, while reducing SOD, TAS, and VEGF expression. Bcl-2 mRNA was not significantly reduced by I/R compared with SHAM; however, BPC 157 significantly increased Bcl-2 expression compared with IR. In the IRB group, BPC 157 reduced MDA and TOS, restored SOD and TAS, downregulated p53, Bax, and Casp3, reduced IL-6 and Caspase-3 immunoreactivity, and partially restored VEGF expression. Histological analysis confirmed improved muscle architecture and reduced collagen deposition in IRB compared with IR. BPC 157 appears to exert protective effects against skeletal muscle I/R injury by attenuating oxidative stress, modulating apoptosis, reducing inflammation, and supporting angiogenic activity. These findings suggest that BPC 157 may represent a potential therapeutic candidate for mitigating reperfusion injury; however, further studies with larger cohorts and dose-response evaluations are required to confirm these effects and establish clinical relevance.
Efficacy and acceptability of liraglutide for obesity in people with HIV: results of an open-label clinical trial in South Africa.
Clin Infect Dis
Ngundu Behuhuma, Gugulethu Gasa, Anne Derache +15 more
In the Liraglutide for Obesity in HIV (LIROH) trial, we evaluated the efficacy and acceptability of liraglutide plus lifestyle counselling on weight and cardiometabolic health markers, along with the effect of discontinuation of therapy, among people with HIV (PWH) and a body mass index (BMI) ≥ 30 kg/m2 in rural South Africa.
Multi-omic profiling reveals Retatrutide alleviates adipose tissue fibrosis via metabolic reprogramming and tissue repair.
Diabetol Metab Syndr
Qingyang Li, Weilun Cheng, Jingyan Zhang +9 more
Retatrutide, a novel GIP, GLP-1, and glucagon receptor triple agonist, exhibits unprecedented weight-reducing efficacy in clinical trials, yet the molecular basis of its systemic metabolic benefits remains unclear.