A microprotein called adipogenin, consisting of 80 amino acids, plays a pivotal role in promoting lipid droplet formation and healthy lipid storage in fat cells.

Adipogenin binds primarily to the seipin complex, and cryo-electron microscopy shows this interaction reinforces seipin’s structure to stabilize the fat storage machinery and facilitate lipid droplet growth.

The imaging also demonstrates that adipogenin makes the seipin complex more rigid and stable, enabling the formation of larger lipid droplets and greater fat storage in adipocytes.

The research was conducted by UT Southwestern Medical Center with collaborators from the University of Helsinki, led by Chao Li and Xue-Nan Sun as co-first authors and Elina Ikonen as co-senior author, supported by NIH funding and various foundations.

Findings point toward clinical applications by identifying a novel target to modulate fat storage and improve metabolic health.

The study, conducted using mice and advanced imaging, investigates adipogenin’s role in lipid metabolism and was led by UT Southwestern and Helsinki researchers.

Researchers suggest adipogenin could be a druggable lever to modulate healthy fat storage and potentially mitigate obesity, diabetes, lipodystrophy, and fatty liver disease.

In practical terms, adipogenin could be targeted to dampen harmful fat buildup or enhance healthy adipose storage, with broad implications for metabolic disease.

UT Southwestern researchers identified adipogenin as a key player in fat cells’ lipid storage, with the microprotein promoting lipid droplet formation.

In mouse models, overproduction of adipogenin led to larger lipid droplets and increased fat storage, while adipogenin deficiency resulted in smaller droplets and less fat.

The work underscores the broader clinical relevance of controlled lipid storage to metabolic health and disease risk.

The findings were published in Science and utilized UT Southwestern’s Cryo-Electron Microscopy Facility as a core part of the study’s methodology.