Effect of β-Estradiol on Adipogenesis in a 3T3-L1 Cell Model of Prelamin A Accumulation

• Published in: International journal of molecular sciences 2024-01, Vol.25 (2), p.1282
• Main Authors: Cobelo-Gómez, Silvia, Sánchez-Iglesias, Sofía, Fernández-Pombo, Antía, Araújo-Vilar, David
• Format: Article
• Language: English
• Subjects: 17-β estradiol; 3T3-L1 Cells; Adipocytes; Adipogenesis; AFCMe; Amino acids; Animals; Body fat; Cardiovascular disease; Cysteine; Enzymes; Estradiol; Estradiol - pharmacology; Estrogens; Female; FTI-277; Fulvestrant; Gene expression; Genes; Hormones; Humans; Lamin Type A; Lipids; Lipodystrophy, Familial Partial - genetics; Lipodystrophy, Familial Partial - metabolism; LMNA; Mice; Microscopy; Nuclear Proteins - genetics; Phenols; prelamin A; Proteins; Puberty
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25021282

The accumulation of farnesylated prelamin A has been suggested as one of the mechanisms responsible for the loss of fat in type 2 familial partial lipodystrophy due to variants in the gene. In this rare disease, fat loss appears in women after puberty, affecting sex-hormone-dependent anatomical areas. This study investigated the impact of 17-β-estradiol on adipogenesis in murine preadipocytes subjected to a pharmacologically induced accumulation of farnesylated and non-farnesylated prelamin A. To induce the accumulation of non-farnesylated or farnesylated prelamin A, 3T3-L1 cells were treated with the farnesyltransferase inhibitor 277 or the methyltransferase inhibitor N-acetyl-S-farnesyl-l-cysteine methylester. Subsequently, the cells were induced to undergo adipocyte differentiation in the presence or absence of 17-β-estradiol. Prelamin A accumulation was assessed through immunofluorescence, while real-time PCR and Western blot techniques were used to quantify several adipogenic genes and evaluate protein levels, respectively. The results showed that 17-β-estradiol increased adipogenesis, although the combination of this hormone plus farnesylated prelamin A led to a reduction in the number of mature adipocytes and the expression of the different genes involved in adipogenesis. In conclusion, the influence of farnesylated prelamin A accumulation on adipogenesis manifested only in the presence of estradiol. These in vitro findings suggest a potential mechanism that could explain the characteristic phenotype in women suffering type 2 familial partial lipodystrophy.