Hosseini Motahare-Sadat, Barjesteh Fereshteh, Azedi Fereshteh, Alipourfard Iraj, Rezaei Zahra, Bahreini Elham
Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
BMC Gastroenterol. 2025 Apr 16;25(1):263. doi: 10.1186/s12876-025-03863-6.
The higher prevalence of non-alcoholic fatty liver disease (NAFLD) in men than women before menopause and the reduced difference post-menopause suggest that sex hormones may influence liver lipid accumulation. This study compared the effects of sex hormones on lipid droplet (LD) accumulation in palmitate/ oleate-treated HepG2 cells.
The MTT method was used to determine effective doses of palmitic and oleic acids in HepG2 cells, followed by a combined dose for inducing LD formation. Changes in LD content after treatment with various doses of β-estradiol and testosterone were evaluated qualitatively and semi-quantitatively using Oil Red O staining and light microscopy. The effects of these hormones on gene expression related to LD formation and lipogenesis, including PLIN2, ATGL, CGI-58, and CIDEB, were assessed using quantitative PCR.
Treatment of HepG2 cells with palmitate and oleate increased LD accumulation and the expression of PLIN2 and CIDE while elevating ATGL expression without affecting CGI-58. With no significant difference, both β-estradiol and testosterone significantly reduced LD accumulation in steatotic HepG2 cells. Gene analysis indicated that both hormones decreased PLIN2 and increased CGI-58 expression. Testosterone did not affect CIDE, while β-estradiol reduced it at low doses. Combined treatment showed no significant changes in gene expression compared to individual hormone effects, but LD accumulation was synergistically reduced.
This study demonstrates that β-estradiol and testosterone significantly modulate LD content and the expression of key regulatory genes in HepG2 cells, with β-estradiol showing a somewhat dominant role in enhancing lipid turnover and mitigating lipid accumulation.
非酒精性脂肪性肝病（NAFLD）在绝经前男性中的患病率高于女性，而绝经后这种差异减小，这表明性激素可能影响肝脏脂质蓄积。本研究比较了性激素对棕榈酸/油酸处理的HepG2细胞中脂滴（LD）蓄积的影响。
采用MTT法测定棕榈酸和油酸在HepG2细胞中的有效剂量，然后采用联合剂量诱导LD形成。使用油红O染色和光学显微镜对不同剂量的β-雌二醇和睾酮处理后的LD含量变化进行定性和半定量评估。使用定量PCR评估这些激素对与LD形成和脂肪生成相关的基因表达的影响，包括PLIN2、ATGL、CGI-58和CIDEB。
用棕榈酸和油酸处理HepG2细胞增加了LD蓄积以及PLIN2和CIDE的表达，同时提高了ATGL表达，而不影响CGI-58。β-雌二醇和睾酮均显著降低了脂肪变性的HepG2细胞中的LD蓄积，无显著差异。基因分析表明，两种激素均降低了PLIN2表达并增加了CGI-58表达。睾酮不影响CIDE，而β-雌二醇在低剂量时降低了CIDE表达。联合处理与单独激素作用相比，基因表达无显著变化，但LD蓄积协同降低。
本研究表明，β-雌二醇和睾酮显著调节HepG2细胞中的LD含量和关键调控基因的表达，β-雌二醇在增强脂质周转和减轻脂质蓄积方面显示出一定的主导作用。
