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Nutrition-First Support for GLP-1 and Dual Incretin Therapy in Obesity: A Practical Framework for Dietary Management, Symptom Tolerability, and Long-Term Weight Maintenance.
Nutrients
Raynier Zambrano-Villacres, Martín Campuzano-Donoso, Claudia Reytor-González +6 more
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed obesity treatment, producing substantial weight loss during active therapy. However, real-world effectiveness may be limited by gastrointestinal adverse events, reduced dietary intake, fat-free mass loss as part of total weight reduction, and weight regain after discontinuation.
GLP-1RA- and Incretin-Based Therapies Within Lifestyle Interventions for Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis.
Nutrients
Alejandro Bruna-Mejias, Juan José Valenzuela-Fuenzalida, Gustavo Oyanedel +5 more
Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity.
GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists in Children and Adolescents with Obesity: Clinical Outcomes and the Impact of Nutritional and Behavioral Co-Interventions-A Systematic Review.
Nutrients
Dominika Myśliwczyk, Krzysztof Ksawery Gofron, Andrzej Wasilewski +2 more
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes (T2D), are increasingly used for the management of overweight and obesity in children and adolescents. However, the impact of concomitant lifestyle interventions, which vary in scope, structure, and intensity, remains unclear. Methods: A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted from April to December 2025 (last update: 12 December 2025), in accordance with the PRISMA 2020 statement. Randomized and observational studies including patients aged 6-19 years with overweight or obesity, with or without T2D, treated with GLP-1 RAs or dual GIP/GLP-1 agonists, were included. Anthropometric outcomes, metabolic parameters, and the scope and structure of concomitant nutritional and behavioral interventions were assessed. Results: Fifteen studies (12 interventional [RCT/non-RCT] and 3 observational), including 1448 participants, were analyzed: liraglutide (n = 6), exenatide (n = 5), semaglutide (n = 1), dulaglutide (n = 1), tirzepatide (n = 1), and lixisenatide (n = 1). Intervention duration ranged from 6 to 68 weeks. Reported BMI reductions varied across studies and pharmacological agents, with semaglutide trials reporting reductions of up to -16.1%. Lifestyle interventions were heterogeneously reported, ranging from general dietary advice to structured, multidisciplinary programs including nutritional counseling, physical activity, and behavioral or family support. Due to heterogeneity in study design and reporting, the independent contribution of lifestyle interventions could not be determined. Conclusions: Available evidence suggests that GLP-1 RAs may represent an effective therapeutic option for children and adolescents with obesity and metabolic disorders. However, available evidence is largely derived from studies incorporating inconsistently reported lifestyle interventions, limiting the ability to disentangle pharmacological and lifestyle effects. Standardized reporting and studies specifically designed to assess their independent and combined effects are needed. Future research should standardize the reporting of lifestyle protocols (e.g., using TIDieR), incorporate validated measures of eating behavior, food preferences, and dietary intake, and use designs (e.g., factorial or stratified randomization of lifestyle intensity) that allow for the pharmacological and behavioral contributions to be quantified separately. This review highlights a critical and previously underexplored methodological gap regarding the structure and reporting of lifestyle co-interventions in pediatric GLP-1 trials.
Intrinsic and extrinsic regulators of cancer dormancy and awakening.
J Natl Cancer Cent
Jingwei Zhang, Md Imtiaz Khalil, Ranjan Mishra +3 more
Metastatic relapse is frequently driven by dormant disseminated tumor cells (DTCs) that previously evaded initial therapy, disseminated to distant tissues, entered into a non-proliferative state termed dormancy, and later reawakened to reinitiate active proliferation and the outgrowth of macroscopic metastases. Cancer dormancy manifests itself in two principal forms: cellular dormancy, characterized by the reversible, proliferative quiescence of individual cells, and tumor mass dormancy, defined by a balance between proliferation and compensating cell death. Dormant cells are notably resistant to conventional therapies and immune-mediated clearance, yet retain viability and the potential to re-enter the active cell cycle. The present review focuses on dormancy of DTCs residing in distant tissues and highlights recent advances in our understanding of both cell-intrinsic and -extrinsic regulators of cancer dormancy. Key cell-autonomous mechanisms include ERK/p38 signaling ratios, epithelial-mesenchymal plasticity, and Wnt signaling. At the same time, signals received by dormant DTCs from the adjacent tissue microenvironment-such as TGF-β family cytokines, immune surveillance, and other stromal interactions-induce and sustain dormancy. Importantly, emerging evidence suggests that microenvironmental conditions, including inflammation and aging, can trigger the awakening of dormant DTCs, leading to metastatic outgrowth. We review these evolving insights into the molecular and environmental control of cancer dormancy and awakening, underscoring their clinical relevance and therapeutic potential in preventing metastatic recurrence.
Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.
Mol Biomed
Nan-Nan Wang, Zhi-Jun Liu, Yong Wang +2 more
The glymphatic system is a brain-wide metabolic clearance pathway, orchestrating the removal of neurotoxic wastes via glial-dependent perivascular networks. Mediated by polarized aquaporin-4 (AQP4) channels on astrocytic end-feet, this macroscopic system drives the convective exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF), establishing a functional coupling between the central nervous system (CNS) and the adaptive immune system. Emerging evidence highlights that glymphatic dysfunction act as both a consequence and a driver of numerous neurological disorders. Neurological pathologies, including neuroinflammation and gliovascular remodeling, compromise the structural and functional integrity of glymphatic architectures. Conversely, glymphatic dysfunction exacerbates neurotoxic wastes accumulation, accelerates disease progression, and perpetuates a pathological positive-feedback loop. Despite growing recognition of this bidirectional relationship, the precise mechanisms remain incompletely understood, and targeted therapeutic strategies are still lacking. In this review, we map the functional architecture of this pathway, from periarteriolar CSF influx to perivenous efflux, and dissect its dependence on critical modulators including sleep-wake rhythms, arterial pulsatility, and aging. Furthermore, we explore novel therapeutic interventions, ranging from AQP4-targeted pharmacological modulation to non-invasive physical approaches, and evaluate their potential to shift clinical paradigms from symptomatic management to disease modification.
Aging Slows Maximum Shortening Velocity and Reduces Peak Power Output of Rat Diaphragm Muscle.
J Appl Physiol (1985)
Genesis Hernandez-Vizcarrondo, Matthew J Fogarty, Humzah Abdulkader +3 more
Sarcopenia is the age-related atrophy and weakening (decrease in force per cross-sectional area) of muscle fibers. In rat diaphragm muscle (DIAm), sarcopenia primarily affects type IIx/IIb fibers that generate greater specific force, have the fastest maximum shortening velocities (Vmax), but display greater fatigue with repeated activation. We hypothesized that because of the selective effect of sarcopenia on type IIx/IIb DIAm fibers, Vmax and peak power output of the DIAm decreases in old age, while endurance during repetitive isovelocity shortening is unaffected. Mid-costal DIAm strips were excised from 6-month (n=8; 4 female and 4 male) and 24-month (n=8; 4 female and 4 male) Fischer 344 rats. The DIAm was supramaximally stimulated using platinum plate electrodes to measure mechanical and endurance properties at 26oC. In 24- compared to 6-month old rats, maximum specific force of the DIAm decreased by ~35%, Vmax slowed by ~20%, and peak power output was reduced by ~35%. During repetitive isovelocity (~30% Vmax; approximating peak power output) contractions, endurance (the period during which power output was sustained) of the DIAm was not different between 6- and 24-month rats. The changes in DIAm mechanical properties corresponded to an age-related decline in the cross-sectional area of type IIx/IIb muscle fibers (~35%). We conclude that age-related atrophy of type IIx/IIb DIAm fibers underlies the changes in mechanical properties of the DIAm, which would only impact more forceful expulsive airway clearance and voiding behaviors of the DIAm. The resilience of type I and IIa DIAm fibers with aging ensures that force generation and endurance required for breathing is sustained in old age.
Comparative effects of sacubitril/valsartan versus enalapril on QRS duration and cardiac function in heart failure patients undergoing left bundle branch area pacing.
Pak J Pharm Sci
Rui Wang, Cuijun Hao, Zhiqin Fang +2 more
Left bundle branch area pacing (LBBaP) has emerged as a physiological pacing strategy for cardiac resynchronization therapy in patients with heart failure (HF) and left bundle branch block (LBBB). However, evidence comparing different pharmacological regimens following LBBaP implantation remains limited.
Complex CTO Revascularization in Patients with Ischemic Heart Failure and Reduced Ejection Fraction: An Illustrative Case Series.
J Clin Med
Ioana Paula Blaj-Tunduc, Mihnea-Traian Nichita-Brendea, Vlad-Victor Babes +2 more
Background/Objectives: Revascularization of chronic total occlusions (CTO) in patients with heart failure and reduced ejection fraction (HFrEF) remains controversial, as randomized trials have not demonstrated a clear prognostic benefit. Methods: We present an imaging-guided case series of patients with ischemic HFrEF who underwent CTO percutaneous coronary intervention (PCI) following myocardial viability assessment using single-photon emission computed tomography (SPECT). Contemporary antegrade and retrograde techniques were employed. Results: At 6- and 12-month follow-ups, all patients demonstrated marked improvement in NYHA (New York Heart Association) functional class, significant reductions in NT-proBNP (N-terminal pro-brain natriuretic peptide) levels, and substantial improvement in quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). These benefits occurred despite only modest improvement in left ventricular (LV) ejection fraction (EF) and limited reverse remodeling. SPECT enabled identification of viable but ischemic myocardium, supporting individualized revascularization decisions. Conclusions: In selected high-risk patients with ischemic HFrEF, CTO-PCI was associated with meaningful clinical and biomarker improvement independent of substantial EF recovery. Careful patient selection, incorporating myocardial viability assessment, may refine individualized clinical decision-making in selected patients. These findings support an imaging-guided approach and warrant further prospective evaluation.
Sacubitril/Valsartan Improves Functional Capacity and Reverses LV Remodeling in Obese Patients with Hypertrophic HFpEF: A Randomized Open-Label Study.
J Clin Med
Artem Ovchinnikov, Alexandra Potekhina, Anastasiya Shchendrygina +5 more
Background: Heart failure with preserved ejection fraction (HFpEF) has multiple phenotypic manifestations with heterogeneous treatment responses. Objective: To evaluate the effect of sacubitril/valsartan (Sac/Val) on functional capacity and cardiac remodeling in overweight/obese HFpEF patients with concentric left ventricular hypertrophy (LVH). Methods: Sixty-one overweight/obese HFpEF patients (body mass index ≥ 25 kg/m2) with hypertensive LVH (LV mass index ≥ 115 g/m2 for men or ≥94 g/m2 for women) were randomized to Sac/Val (100-400 mg a day; n = 30) versus the usual care group (n = 31) for 6 months. Changes in six-minute walk test distance (6MWTD) were the primary outcomes. Secondary outcomes included changes in echocardiographic parameters of cardiac structure and function, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Results: After 6 months of Sac/Val therapy, 6MWTD increased, and E/e' ratio, LV mass index, LA volume index, and NT-proBNP levels decreased compared with the usual care group (p < 0.05 for all). Conclusions: In overweight/obese patients with HFpEF and LVH, Sac/Val significantly improved functional capacity and reduced LV mass and filling pressure compared with standard medical therapy.
Expression and Correlation Analysis of Neuropeptide Family Members in the Peripheral Blood of Patients with COVID-19.
Curr Pediatr Rev
Hong Wei Li, Shang Zhi Wu, Si Xiang Tang +5 more
The purpose of this article is to investigate the expression of neuropeptide family members and their correlation with inflammatory indicators in the peripheral blood of children infected with COVID-19.
Lentiviral GLP-1 gene therapy elicits developmental stage-dependent β-cell regeneration in diabetic rats.
J Mol Med (Berl)
Ezgi Erbasan, Melike Aliciaslan, Fulya Erendor +4 more
Pancreatic β-cell differentiation and regenerative capacity differ markedly between developmental stages, with the neonatal pancreas exhibiting high plasticity that enables ongoing progenitor- and ductal-derived β-cell formation, whereas the adult pancreas demonstrates limited neogenic potential. Glucagon-like peptide-1 (GLP-1) promotes β-cell survival, proliferation, and differentiation; however, its developmental stage-specific effects on β-cell regeneration are not fully understood. To investigate this, we generated a third-generation HIV-based lentiviral vector encoding native GLP-1 (LentiGLP-1) under the control of cytomegalovirus (CMV) promoter using the Multisite Gateway® recombination cloning system. The vector's ability to modulate β-cell differentiation and proliferation was subsequently assessed in neonatal and adult diabetic rat models. Type 2 Diabetes (T2DM) was induced in neonatal rats by administering low-dose streptozotocin (STZ), exploiting the intrinsic plasticity of the developing pancreas, whereas in adult rats, a high-fat diet combined with low-dose STZ was used. LentiGLP-1 administration markedly promoted differentiation of ductal and progenitor cells into insulin-producing β-cells in neonatal rats, accompanied by enhanced β-cell proliferation, demonstrating effective engagement of developmental plasticity. In adults, LentiGLP-1 partially restored β-cell populations through activation of residual progenitors and stimulation of replication in existing β-cells, improving glycemic control and insulin sensitivity. Notably, acinar cells did not contribute to β-cell generation in either neonatal or adult models. These results indicate that GLP-1 exerts developmentally regulated effects on β-cell differentiation, facilitating neogenesis in neonates and partially restoring regenerative capacity in adults. Long term GLP-1 expression, thus represents a promising strategy to restore β-cell mass by proliferation and differentiation, providing insight into its therapeutic potential for diabetes.
Benefits of Incretin Therapy on Ovarian Function: A Scientific Literature Review.
Int J Mol Sci
Sandro La Vignera, Rosita A Condorelli
Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have emerged as potentially promising therapeutic agents for improving ovarian function, especially in women with polycystic ovary syndrome (PCOS) and obesity-related reproductive dysfunction. This comprehensive review synthesizes evidence from 30 highly relevant studies examining the mechanisms of action, clinical outcomes, and safety profile of incretin therapies on ovarian function. The evidence suggests that GLP-1 RAs may exert beneficial effects through multiple molecular pathways, including FOXO1 signaling, modulation of steroidogenesis, and enhancement of insulin sensitivity, although most mechanistic data derive from animal models and in vitro studies without validation in human ovarian tissue. Clinical outcomes from randomized controlled trials and meta-analyses show improvements in menstrual regularity, hormonal profiles, and spontaneous conception rates, though evidence certainty is limited by small sample sizes, short duration, high heterogeneity, and restriction to overweight/obese populations. While preliminary safety data regarding inadvertent early pregnancy exposure are reassuring, animal studies suggest potential dose-dependent risks that warrant careful consideration. Importantly, GLP-1 RAs are not currently approved or guideline-recommended for fertility restoration, and substantial uncertainty remains regarding long-term reproductive safety, optimal patient selection, and clinical guidelines. This review provides a balanced synthesis of current evidence and identifies critical gaps requiring further investigation before routine clinical use can be recommended.
Differential Modulation of Postprandial Glycemic, Incretin, and Satiety Responses by Low-Digestible Carbohydrates in Humans: An Exploratory Investigation.
Nutrients
Jinsoo Noh, Hye Rim Kim, Jungsook Han +6 more
Effective postprandial glycemic regulation is essential for preventing metabolic disorders such as type 2 diabetes. While pharmacological interventions like GLP-1 (Glucagon-Like Peptide-1) receptor agonists are effective, dietary strategies using low-digestible carbohydrates (LDCs) may offer a sustainable and complementary approach.
Impact of the Cosecretion of Cortisol on Surgical Outcomes and in the Urinary Steroid Profile in Primary Aldosteronism.
Endocr Pract
Marta Araujo-Castro, Gregori Casals, Jessica Goi +9 more
To analyze if there are differences in the urinary steroid profile before and after cosyntropin stimulation and in the surgical outcomes between patients with primary aldosteronism (PA) with associated mild autonomous secretion of cortisol (MACS) (MACS-PA) and those without it (only PA).
The role of endoscopic therapies for patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Expert Rev Gastroenterol Hepatol
Joan Llach, Anna Soria, Isabel Graupera +1 more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health challenge closely linked to obesity and metabolic syndrome. Effective, durable weight-loss strategies are needed to modify its natural history, particularly in patients at high surgical risk or with limited response to pharmacotherapy.
Development of bacterial cellulose-based polymeric cryogel scaffold as an eco-friendly biomaterial.
Colloids Surf B Biointerfaces
Hao An, Hyun-Woo Choi, Yong-Seok Jang +2 more
Cryogels with interconnected macroporous structures are promising three-dimensional scaffolds that facilitate cell infiltration, nutrient transport, and tissue development. This study compared two cryogel systems: gelatin methacryloyl cryogels prepared by free-radical polymerization and oxidized bacterial cellulose-gelatin cryogels synthesized through a green, initiator-free Schiff-base crosslinking method. Both scaffolds exhibited favorable elasticity and biocompatibility, but oxidized bacterial cellulose-gelatin cryogels maintained stable pore structures upon rehydration and showed superior mechanical integrity due to the nanofibrous cellulose framework. Murine preosteoblasts cultured on oxidized bacterial cellulose-gelatin scaffolds exhibited enhanced proliferation and osteogenic differentiation, attributed to optimal pore size and the absence of cytotoxic crosslinking residues. Furthermore, Bovine muscle satellite cells exhibited better spreading and a denser PAX7-positive distribution on oxidized bacterial cellulose-gelatin cryogels, suggesting that the stable porous architecture may support satellite cell maintenance and expansion. These findings demonstrate that tuning pore architecture and using biocompatible crosslinking chemistry significantly improve cryogel scaffold performance. The oxidized bacterial cellulose-gelatin cryogel presents a promising, versatile platform for both hard and soft tissue engineering applications.
Effect of supplemental hydrocortisone during stress in prednisolone-induced adrenal insufficiency: a study protocol for a multicentre, randomised, double-blinded, placebo-controlled clinical trial on health-related quality of life in patients with polymyalgia rheumatica/giant cell arteritis on low-dose prednisolone treatment (the RESCUE study).
BMJ Open
Stina Willemoes Borresen, Simon Bøggild Hansen, Hajir Al-Jorani +15 more
Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone.
A unimolecular GLP-1 and FGF21 dual agonist for treatment of metabolic dysfunction-associated steatohepatitis.
Commun Med (Lond)
Parul Sirohi, Seh-Hoon Oh, Catherine G Price +7 more
Metabolic dysfunction-associated steatohepatitis is a progressive liver disease characterized by inflammation and fibrosis, for which effective pharmacological treatments remain limited. Hormones that regulate metabolism, such as glucagon-like peptide-1 and fibroblast growth factor-21, have shown therapeutic promise through complementary metabolic and hepatoprotective actions. This study aims to develop and evaluate a single molecular therapy that engages both pathways to address multiple drivers of disease progression.
LncRNA TUG1 promotes hypertrophic scar formation via the miR-627/IGF1R axis.
J Mol Histol
Zeming Bai, Ziyang Han, Xiangzi Kong +7 more
Hypertrophic scars (HS) are fibrotic skin disorders driven by abnormal fibroblast activity. The molecular mechanisms underlying HS remain incompletely understood, particularly the role of non-coding RNAs. Expression levels of lncRNA TUG1, miR-627, and IGF1R were measured in HS tissues and fibroblasts using qRT-PCR and Western blotting. Dual-luciferase assays validated direct interactions. Functional effects of TUG1 and miR-627 on fibroblast proliferation and migration were assessed using MTT and Transwell assays. A rabbit ear model of HS was used to examine in vivo effects of TUG1 and miR-627 modulation on scar formation and molecular expression. TUG1 was significantly upregulated in HS tissues and inversely correlated with miR-627, which was downregulated. TUG1 promoted fibroblast proliferation and migration by directly sponging miR-627, thereby lifting repression on IGF1R, a known pro-fibrotic effector. Luciferase assays confirmed direct binding of miR-627 to both TUG1 and IGF1R. Co-transfection of miR-627 attenuated TUG1-induced IGF1R upregulation and reversed its pro-fibrotic cellular effects. In vivo, TUG1 overexpression led to increased scar thickness, collagen deposition, and IGF1R expression, while miR-627 overexpression mitigated these effects. Co-administration of both restored scar morphology and molecular markers to near-control levels. TUG1 promotes hypertrophic scar formation by sponging miR-627 and derepressing IGF1R. This newly identified TUG1-miR-627-IGF1R axis plays a central role in HS pathogenesis and may serve as a promising therapeutic target for fibrotic skin disease.
Serum from Fibromyalgia Patients Activates Satellite Glial Cells in Mouse Peripheral Ganglia.
Cells
Menachem Hanani, Rachel Feldman-Goriachnik, Suhail Aamar
Fibromyalgia (FM) is a complex syndrome associated with chronic widespread pain and with various other symptoms, including sleep and mood disturbances. Its underlying causes are not fully understood, and the lack of diagnostic blood tests and imaging, along with the absence of definitive treatments, makes management challenging. Recent studies showed that passive transfer of immunoglobulins from FM patients into mice activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG), leading to pain behaviors. Here, we aimed to determine whether whole serum from FM patients activates mouse SGCs in DRGs and other ganglia that may be involved in FM's diverse symptoms. Serum from FM patients (N = 15) and healthy controls (HCs, N = 8) was collected. Sera were incubated with different types of mouse sensory ganglia: DRG, trigeminal ganglion (TG), the nodose ganglion (NG), and the superior cervical sympathetic ganglion (Sup-CG). SGC activation was assessed by immunostaining of SGCs for the glial activation marker glial fibrillary acidic protein (GFAP). All the ganglia tested, DRG, TG, NG, and Sup-CG, displayed induced upregulation of GFAP labeling in SGCs after incubation with FM serum compared with HCs, indicating SGC activation by the serum. Similar responses were observed in both male and female mice. We conclude that serum from FM patients contains factors that can activate SGCs across various types of mouse ganglia, which may reflect the diverse symptom profile of FM. These findings provide evidence for pathogenic factors that could serve as a foundation for a diagnostic method for FM and require further purification and identification, hopefully paving the way for future targeted FM therapy.