Department of Food and Nutrition, Mokpo National University, Muan-gun 58554, Korea.
Nutrition Research Institute, University of North Carolina, Chapel Hill, NC 28081, USA.
Nutrients. 2022 Oct 12;14(20):4247. doi: 10.3390/nu14204247.
Although the red pepper and its seeds have been studied for metabolic diseases, the effects and potential mechanisms of red pepper seed extract (RPS) on hepatic lipid accumulation are not yet completely understood. This study aimed to evaluate the inhibitory effect of RPS on hepatic lipid accumulation via autophagy. C57BL/6 mice were fed a high-fat diet (HFD) or a HFD supplemented with RPS. RPS treatment inhibited hepatic lipid accumulation by suppressing lipogenesis, inducing hepatic autophagic flux, and activating AMPK in HFD-fed mice. To investigate the effect of RPS on an oleic acid (OA)-induced hepatic steatosis cell model, HepG2 cells were incubated in a high-glucose medium and OA, followed by RPS treatment. RPS treatment decreased OA-induced lipid accumulation and reduced the expression of lipogenesis-associated proteins. Autophagic flux dramatically increased in the RPS-treated group. RPS phosphorylated AMPK in a dose-dependent manner, thereby dephosphorylated mTOR. Autophagy inhibition with 3-methyladenine (3-MA) antagonized RPS-induced suppression of lipogenesis-related protein expressions. Moreover, the knockdown of endogenous AMPK also antagonized the RPS-induced regulation of lipid accumulation and autophagy. Our findings provide new insights into the beneficial effects of RPS on hepatic lipid accumulation through the AMPK-dependent autophagy-mediated downregulation of lipogenesis.
虽然红辣椒及其种子已被用于研究代谢性疾病，但红辣椒籽提取物（RPS）对肝脂质积累的影响和潜在机制尚未完全阐明。本研究旨在通过自噬评估 RPS 对肝脂质积累的抑制作用。C57BL/6 小鼠喂食高脂肪饮食（HFD）或 HFD 补充 RPS。RPS 处理通过抑制脂肪生成、诱导肝自噬流和激活 HFD 喂养小鼠中的 AMPK 来抑制肝脂质积累。为了研究 RPS 对油酸（OA）诱导的肝脂肪变性细胞模型的影响，将 HepG2 细胞在高葡萄糖培养基和 OA 中孵育，然后用 RPS 处理。RPS 处理可减少 OA 诱导的脂质积累并降低脂肪生成相关蛋白的表达。自噬通量在 RPS 处理组中明显增加。RPS 以剂量依赖性方式磷酸化 AMPK，从而使 mTOR 去磷酸化。用 3-甲基腺嘌呤（3-MA）抑制自噬会拮抗 RPS 诱导的脂生成相关蛋白表达的抑制。此外，内源性 AMPK 的敲低也拮抗了 RPS 诱导的脂质积累和自噬的调节。我们的研究结果为 RPS 通过 AMPK 依赖性自噬介导的脂生成下调对肝脂质积累的有益作用提供了新的见解。
