Comprehensive review establishes obesity as a multifactorial chronic disease driven by genetics, epigenetics, gut peptide hormones, and environmental factors — requiring personalized treatments including GLP-1 drugs, gene therapy, and AI-driven interventions.
5 gut peptide hormones central to obesityLeptin, ghrelin, GLP-1, PYY, and CCK are recognized as pivotal regulators of appetite and weight, forming the biological basis for current and future obesity treatments
What the researchers found
Obesity pathophysiology involves insulin resistance, dyslipidemia, chronic low-grade inflammation, and neuroendocrine dysregulation of appetite. Gut-derived peptide hormones (leptin, ghrelin, GLP-1, PYY, CCK) are pivotal regulators of appetite and weight. Beyond caloric excess, genetic predisposition, epigenetic modifications, gut microbiota dysbiosis, endocrine-disrupting chemicals, circadian misalignment, and prenatal/intergenerational influences are all critical determinants. Advances in molecular profiling and metabolic phenotyping are enabling precise risk stratification and personalized treatment selection.
Why it matters
Obesity is the most prevalent chronic disease globally and drives type 2 diabetes, cardiovascular disease, cancer, and many other conditions. Understanding obesity as a complex biological disease — not just a behavioral problem — is essential for developing effective treatments and reducing stigma. The review places peptide hormone therapies (especially GLP-1 drugs) in the broader context of obesity biology, showing why they work and where future treatments may emerge.
How the study worked
Comprehensive narrative review synthesizing contemporary evidence across molecular biology, genetics, endocrinology, gastroenterology, epidemiology, and digital health. Covers the biological basis, systemic consequences, preventive strategies, and therapeutic modalities of obesity.
What this study cannot tell us
This is a very broad narrative review covering numerous topics at a high level. Individual claims about genetic, epigenetic, and microbiome contributions vary greatly in their strength of evidence. The review doesn't systematically evaluate the quality of evidence for each mechanism. Some discussed therapies (gene therapy, AI platforms) are still largely experimental. The breadth may sacrifice depth on any single topic.
How to read the evidence
This is a broad narrative review covering multiple domains of obesity biology and treatment. While it provides a useful overview, it lacks the focused methodology of a systematic review and covers topics with widely varying levels of evidence.
When this study was published
Published in 2025, this review captures the current understanding of obesity as a complex disease during a period of rapid therapeutic advancement driven by GLP-1-based drugs.
The bigger picture
The framing of obesity as a multifactorial chronic disease has been a paradigm shift in medicine, driven partly by the success of GLP-1 drugs in demonstrating that pharmacological intervention can produce dramatic weight loss. This review captures the current state of that paradigm — from molecular mechanisms to AI-driven personalized treatment — and highlights that the gut peptide hormone system is at the center of both the disease and its treatment.
Questions still open
- Can metabolic phenotyping predict which obesity patients will respond best to GLP-1 drugs versus other interventions?
- How much of obesity risk is determined by prenatal and epigenetic programming versus adult lifestyle factors?
- Will gene therapy approaches for obesity become clinically viable within the next decade?
Common questions
Why is obesity considered a disease and not just a lifestyle choice?
What role do gut hormones play in obesity and its treatment?
Read the original research
Obesity as a Multifactorial Chronic Disease: Molecular Mechanisms, Systemic Impact, and Emerging Digital Interventions.
Current issues in molecular biology, 47(10)
Citation
Młynarska, Ewelina; Bojdo, Kinga; Bulicz, Anna; Frankenstein, Hanna; Gąsior, Magdalena; Kustosik, Natalia; Rysz, Jacek; Franczyk, Beata. (2025). Obesity as a Multifactorial Chronic Disease: Molecular Mechanisms, Systemic Impact, and Emerging Digital Interventions.. Current issues in molecular biology, 47(10). https://doi.org/10.3390/cimb47100787