Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy.
Nicze. Michał M; Dec. Adrianna A; Borówka. Maciej M; Krzyżak. Damian D; Bołdys. Aleksandra A; Bułdak. Łukasz Ł; Okopień. Bogusław B
Key Findings
- Obesity is driven by an energy‑intake vs. expenditure mismatch and involves the brain, gut‑brain axis, gut motility, and energy‑burning pathways.
- GLP‑1 receptor agonists (liraglutide, semaglutide) and the dual GLP‑1/GIP agonist tirzepatide are proven, highly effective weight‑loss drugs with metabolic benefits.
- Research is ongoing on next‑generation peptide drugs that could further improve obesity management.
Practical Outcomes
- For self‑experimenters, GLP‑1‑based drugs are the most evidence‑backed options for significant weight loss and metabolic health. While retatrutide isn’t covered here, it belongs to the same class, so keep an eye on emerging trial data. Use this info to prioritize clinically validated hormone‑mimetic peptides and stay updated on new trial results.
Summary
The paper explains that obesity comes from taking in more calories than you burn and points to several body systems that control appetite and metabolism. It highlights that drugs mimicking gut hormones—especially GLP‑1 drugs like liraglutide and semaglutide, and the newer dual GLP‑1/GIP drug tirzepatide—can cause big weight loss and improve blood sugar. It also notes that new experimental molecules are being tested for future obesity treatments.
Abstract
Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.
Study Information
pubmed
2024
2024-07-27T00:00:00.000Z
10.3390/ijms25158202
8
296