Obesity-Related Gastrointestinal Disorders: Uncovering Mechanisms Behind Cardiometabolic Improvement with Weight Loss

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 3066

Special Issue Editor


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Guest Editor
1. Department of Internal Medicine, Boston Medical Center, Boston, MA, USA
2. Division of Gastroenterology, Mayo Clinic Hospital, Rochester, MN, USA
Interests: endoscopic therapy; obesity; MASLD; IBD

Special Issue Information

Dear Colleagues,

Obesity and its associated cardiometabolic comorbidities remain significant drivers of chronic gastrointestinal (GI) diseases. Recent advances in the field of obesity, including anti-obesity medications (AOMs) and endoscopic/bariatric therapies, demonstrate the potential not only to reduce body weight but also to improve conditions such as type 2 diabetes, hypertension, gastro-esophageal reflux disease (GERD), and metabolic dysfunction-associated steatotic liver disease (MASLD). However, many aspects of how these procedures alter GI physiology and influence systemic metabolisms are still being uncovered.

For this Special Issue, we welcome submissions that elucidate the underlying mechanisms by which weight loss via different modalities (e.g., AOMs and endoscopic procedures) confers cardiometabolic benefits. We encourage articles that explore innovative techniques for weight management and improvements in cardiometabolic health, highlighting the role of gut hormones and investigating how these procedures modulate GI function in the context of broader metabolic health. By focusing on a range of methodological approaches—ranging from basic research to multidisciplinary collaborations—this Special Issue will advance our understanding of the complex relationships among obesity, chronic GI disease, and cardiometabolic risk. By providing a more comprehensive view of these interconnections, the Special Issue will facilitate the development of improved therapeutic strategies for patients with obesity-related GI disorders.

Dr. Wissam Ghusn
Guest Editor

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Keywords

  • metabolic dysfunction-associated steatotic liver disease (MASLD)
  • gastro-esophageal reflux disease (GERD)
  • obesity
  • cardiometabolic comorbidities
  • type 2 diabetes
  • hypertension
  • gut hormones
  • gastrointestinal function

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Published Papers (2 papers)

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Review

16 pages, 842 KB  
Review
Endoscopic Bariatric Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanistic Insights and Metabolic Implications
by Wissam Ghusn, Mira Sridharan, Rachel Fromer, Muhammet Ozdemir, Madeleine G. Haff and Eric J. Vargas
Biomedicines 2025, 13(10), 2437; https://doi.org/10.3390/biomedicines13102437 - 7 Oct 2025
Viewed by 1084
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal resurfacing (DMR), offer minimally invasive interventions that target metabolic dysfunction and weight loss. This review synthesizes current evidence on the mechanisms and hepatic outcomes of EBTs in MASLD, highlighting improvements in hepatic steatosis, liver stiffness, and fibrosis biomarkers across multiple modalities. ESG is consistently associated with reductions in hepatic steatosis and fibrosis scores across multiple studies. IGB therapy improves liver stiffness and reduces hepatic fat as assessed by imaging modalities such as MRI- Proton Density Fat Fraction and ultrasound. DJBL lowers liver enzymes and improves non-invasive markers of steatohepatitis like the Fibroscan-AST score, although its effect on fibrosis appears limited. DMR demonstrates reductions in liver fat, particularly in patients with type 2 diabetes, but evidence for histological improvement in MASLD remains inconsistent. Despite their promise, most EBT studies remain limited by small sample sizes and short follow-up. Further randomized trials are needed to validate long-term efficacy and position EBTs alongside or as alternatives to surgical interventions for MASLD. Full article
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22 pages, 4729 KB  
Review
Structure-Based Insights into TGR5 Activation by Natural Compounds: Therapeutic Implications and Emerging Strategies for Obesity Management
by Dong Oh Moon
Biomedicines 2025, 13(10), 2405; https://doi.org/10.3390/biomedicines13102405 - 30 Sep 2025
Viewed by 1767
Abstract
TGR5 has emerged as a promising therapeutic target for obesity and metabolic disorders due to its regulatory roles in energy expenditure, glucose homeostasis, thermogenesis, and gut hormone secretion. This review summarizes the structural mechanisms of TGR5 activation, focusing on orthosteric and allosteric ligand [...] Read more.
TGR5 has emerged as a promising therapeutic target for obesity and metabolic disorders due to its regulatory roles in energy expenditure, glucose homeostasis, thermogenesis, and gut hormone secretion. This review summarizes the structural mechanisms of TGR5 activation, focusing on orthosteric and allosteric ligand interactions, toggle switch dynamics, and G protein coupling based on cryo-EM and docking-based models. A wide range of bioactive natural compounds including oleanolic acid, curcumin, betulinic acid, ursolic acid, quinovic acid, obacunone, nomilin, and 5β-scymnol are examined for their ability to modulate TGR5 signaling and elicit favorable metabolic effects. Molecular docking simulations using CB-Dock2 and PDB ID 7BW0 revealed key interactions within the orthosteric pocket, supporting their mechanistic potential as TGR5 agonists. Emerging strategies in TGR5-directed drug development are also discussed, including gut-restricted agonism to minimize gallbladder-related side effects, biased and allosteric modulation to fine-tune signaling specificity, and AI-guided optimization of natural product scaffolds. These integrated insights provide a structural and pharmacological framework for the rational design of safe and effective TGR5-targeted therapeutics. Full article
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