Adipogenin-seipin, lipid droplet architecture and the expanding metabolic frontier: Implications for metabolic disorders and cancer
Year: 2025
Type: article
Abstract: Recent work by Li et al. identifying adipogenin as a structural cofactor of seipin introduces a new paradigm in lipid droplet (LD) biology, shifting attention from enzymatic control of lipid synthesis toward organelle architecture as a determinant of metabolic disease. By stabilizing a dodecameric seipin complex, adipogenin redirects triacylglycerol flux from LD nucleation to droplet expansion, thereby promoting LD enlargement, adipocyte hypertrophy and adipose tissue growth. This mechanism refines the adipose tissue expandability hypothesis by highlighting the importance of endoplasmic reticulum-LD interfaces and their associated microproteins in determining lipid storage capacity. Beyond adipose tissue, LDs have emerged as multifunctional organelles in cancer, supporting metabolic flexibility, redox homeostasis, hypoxia adaptation and resistance to cytotoxic therapies. Although adipogenin expression appears restricted to adipocytes, the structural principle it exemplifies, i.e. that small ER-embedded cofactors may modulate seipin assemblies and LD dynamics, may extend to malignant cells through yet-unidentified microproteins. Collectively, these observations position LD architecture as a conceptual model linking obesity, associated metabolic disorders, as well as cancer pathogenesis, suggesting that targeting organelle-level regulation, rather than lipid metabolism alone, may open new avenues for potential therapeutic interventions.
Source: Metabolism Open
Author: Maria Dalamaga
Institution: National and Kapodistrian University of Athens
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,120
OpenAlex ID: W7116896908