Ubiquitination as the key to fighting obesity and diabetes!

Ubiquitination as the key to fighting obesity and diabetes!

New research from the University of Stuttgart sheds light on the crucial role of fat cells in regulating our health. In a study published in the renowned journalScience Advances, the authors investigate the function of linear ubiquitination and its impact on the prevention of lipodystrophy and obesity-associated metabolic syndromes. This could have far-reaching implications for the treatment of obesity and its comorbidities.

The study, published on September 17, 2025, focuses on the linear ubiquitin chain assembly complex (LUBAC). This plays a crucial role in regulating inflammatory processes through NF-κB/MAPK signaling pathways and prevents cell death in human fat cells. Mice models painted by HOIP, the catalytic subunit of LUBAC in fat cells, suffer from lipodystrophy and show increased susceptibility to obesity-related metabolic syndrome.

The role of inflammation and fat cells

Research shows that the hypertrophy of adipocytes that occurs during obesity triggers chronic inflammation and thus leads to metabolic disorders. However, understanding of inflammatory signaling specific to adipose disease remains unclear. The results show that reduced HOIP expression in adipose tissue correlates with poorer metabolic fitness in obesity patients.

In particular, in mice observed in the study, it was discovered that the absence of HOIP not only reduces TNF-induced NF-κB activation but also promotes cell death in the adipocytes. The authors emphasize that inhibition of cell death by caspase-8 may help prevent lipodystrophy and reduce the risk of metabolic-related liver diseases.

Pharmacotherapy for obesity

As obesity continues to be a growing health problem, pharmacotherapy is recommended as an important treatment option. People with a body mass index (BMI) of over 27 kg/m² and comorbidities or over 30 kg/m² without comorbidities should consider drug therapy. Doctors must first thoroughly evaluate comorbidities and medications already taken in order to select the appropriate therapy.

• Hauptklassen von Adipositas-Medikamenten:
• ZNS-Stimulanzien oder Anorexiants (z. B. Phentermin, Lorcaserin)
• Antidepressiva, Dopaminwiederaufnahmehemmer oder Opioidantagonisten (z. B. Bupropion, Naltrexon)
• Gastrointestinale Wirkstoffe (z. B. Orlistat, GLP-1-Agonisten)
• Andere (z. B. Topiramat, Metformin, SGLT2-Hemmer)

The effectiveness of the medications can vary significantly. There are also specific side effects to consider: Orlistat can inhibit fat absorption, but often leads to unpleasant gastrointestinal symptoms. Phentermine, on the other hand, acts as a short-term appetite suppressant, but also has a wide range of possible side effects.

Particular attention is paid to the decreasing effectiveness of some medications: discontinuing long-term medications can often lead to rapid weight gain. It is therefore crucial that patients and doctors work closely together to find the best possible therapy with proven success.

Overall, it is clear that research into the role of fat cells and the associated metabolic diseases is of great importance, both on a molecular and therapeutic level. Future studies could bring important advances in the treatment of obesity and the diseases that result from it.