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Metabolism Discovery of the Year: How Olfactomedin-2 Manages Adipocyte Health and Weight
Last reviewed: 09.08.2025
">Scientists from Spain, China, the UK and Japan have uncovered a mechanism that links the disruption of a single protein to the development of obesity. Their work, published in Nature Communications, demonstrates for the first time that a defect in Olfactomedin-2 (OLFM2) leads to adipocyte dysfunction, provokes inflammation of adipose tissue and causes systemic metabolic disorders.
Key Facts Revealed
- OLFM2 is a secreted glycoprotein: Until this study, the Olfactomedin family was primarily associated with the development of neural tissue and eye diseases. Scientists have demonstrated for the first time its measurable presence and function in adipocytes.
- A mouse model of adipocyte-specific OLFM2 deficiency: transgenic mice lacking OLFM2 only in fat cells rapidly gained weight on a normal diet, exhibited adipocyte hypertrophy, and fat accumulation in the liver.
- Metabolic consequences: KO mice demonstrated pronounced insulin resistance, elevated levels of proinflammatory cytokines (TNF-α, IL-6) and massive macrophage infiltration into fat depots.
- Molecular pathway: In the absence of OLFM2, normal adiponectin secretion and the activity of the key metabolic sensor AMPK were impaired, leading to decreased fatty acid utilization and increased glucose oxidation.
- Human data: In adipose tissue of obese people, OLFM2 levels were half those in lean volunteers and were negatively correlated with body weight, HbA1c levels, and markers of systemic inflammation.
Significance of the study
The discovery of OLFM2 as a critical regulator of adipocytes overturns the notion that obesity is merely a consequence of external factors (diet, activity). It is now clear that defects in one of the secreted adipo-mediators can trigger a cascade of immunometabolic disorders.
This opens up new therapeutic horizons:
- OLFM2 biomimetics (recombinant proteins or small molecules that enhance its function) can restore metabolic balance and reduce body weight in obesity models.
- Gene therapy aimed at increasing OLFM2 expression in fat tissue promises long-term effects in metabolic syndrome and type 2 diabetes.
Prospects and Next Steps
The authors emphasize the need to:
- Depot-specific studies - compare the role of OLFM2 in subcutaneous and visceral fat.
- Testing safe OLFM2 agonists in preclinical and early clinical trials.
- Assessment of systemic effects, as OLFM2 may affect the liver, muscle and central nervous system via endocrine mechanisms.
"We found that Olfactomedin-2 deficiency in adipocytes triggers inflammation of adipose tissue and metabolic collapse of the body. Restoring its level completely normalizes metabolism and improves insulin sensitivity," says lead author of the study Aina Lluch.
In an era when obesity affects more than 650 million people, these findings offer hope for the development of fundamentally new treatments that target not just symptoms, but the root molecule that governs fat cell health.