Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida-Jacksonville, Jacksonville, FL, United States of America.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida-Jacksonville, Jacksonville, FL, United States of America.
Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Aug;1867(8):159155. doi: 10.1016/j.bbalip.2022.159155. Epub 2022 Apr 26.
Black seed extract stimulates apolipoprotein A-I (apo A-I) gene expression in hepatocytes and intestinal cells in part by elevating peroxisome proliferator-activated receptor α (PPARα) and retinoid X receptor α (RXRα) levels. To explore potential ramifications of these observations, we examined the effects of black seed extract on hepatocyte lipid content and expression of key transcriptional regulators of fatty acid β-oxidation and lipogenesis in HepG2 cells. PPARα, peroxisome proliferator-activated receptor γ (PPARγ), RXRα, thyroid hormone receptor β (TRβ), sterol-responsive element binding protein 1 (SREBP1), and sterol-responsive element binding protein 2 (SREBP2) levels were measured in black seed extract treated liver-derived HepG2 cells. Black seed extract treatment increased PPARα and RXRα expression and decreased intracellular neutral lipid content. Black seed extract treatment increased TRβ expression and activity, and PPARα activity. In contrast, PPARγ, SREBP1 and SREBP2 levels were decreased in black seed extract treated cells. Black seed extract treatment also increased acyl-CoA synthetase long chain family member 5 (ACSL5), peroxisomal acyl-CoA oxidase 1 (ACOX1), and carnitine palmitoyl transferase 1A (CPT-1A) expression, three PPARα-dependent rate-limiting genes that facilitate fatty acid oxidation, similar to fenofibrate. PPARα knockdown reversed the effects of fenofibrate and blackseed on ACSL5, ACOX1, and CPT-1A expression. In conclusion, black seed extract-mediated lipid lowering in HepG2 cells is associated with increased expression of fatty acid oxidation enzymes and PPARα and reduced lipogenic signaling. Thus black seed extract may be potentially beneficial in metabolic diseases such as diabetes, cardiovascular disease, and metabolic syndrome.
黑种草提取物通过提高过氧化物酶体增殖物激活受体α（PPARα）和视黄醇 X 受体α（RXRα）水平，部分刺激肝细胞和肠细胞中的载脂蛋白 A-I（apo A-I）基因表达。为了探索这些观察结果的潜在影响，我们研究了黑种草提取物对 HepG2 细胞中肝细胞脂质含量和脂肪酸β-氧化和脂肪生成关键转录调节因子表达的影响。在黑种草提取物处理的肝源性 HepG2 细胞中测量了过氧化物酶体增殖物激活受体γ（PPARγ）、RXRα、甲状腺激素受体β（TRβ）、固醇反应元件结合蛋白 1（SREBP1）和固醇反应元件结合蛋白 2（SREBP2）的水平。黑种草提取物处理增加了 PPARα 和 RXRα 的表达，并降低了细胞内中性脂质含量。黑种草提取物处理增加了 TRβ 的表达和活性，以及 PPARα 的活性。相比之下，黑种草提取物处理的细胞中 PPARγ、SREBP1 和 SREBP2 的水平降低。黑种草提取物处理还增加了长链酰基辅酶 A 合成酶 5（ACSL5）、过氧化物酶体酰基辅酶 A 氧化酶 1（ACOX1）和肉碱棕榈酰转移酶 1A（CPT-1A）的表达，这三个都是促进脂肪酸氧化的 PPARα 依赖性限速基因，与非诺贝特类似。PPARα 敲低逆转了非诺贝特和黑种草对 ACSL5、ACOX1 和 CPT-1A 表达的影响。总之，黑种草提取物在 HepG2 细胞中的降脂作用与脂肪酸氧化酶和 PPARα 的表达增加以及脂肪生成信号的减少有关。因此，黑种草提取物在糖尿病、心血管疾病和代谢综合征等代谢性疾病中可能具有潜在益处。
