Hong Kexin, Wang Jiting, Kang Xiping, Xue Huimin, Gao Yunxiao, Liang Heming, Huang Weidong, Zhan Jicheng, You Yilin
College of Food Science and Nutritional Engineering, Beijing Key Laboratory of Viticulture and Enology, China Agricultural University, Tsinghua East Road 17, Haidian District, Beijing, 100083, China.
Food Funct. 2025 Jan 2;16(1):40-53. doi: 10.1039/d4fo02955k.
Dietary phenolic acids can combat metabolic diseases like obesity and non-alcoholic fatty liver by enhancing adipose tissue's thermogenic function. Uncoupling protein 1 (UCP1), a key thermogenic protein, is linked to atherosclerosis (AS) development. Whether dietary phenolic acids inhibit AS by boosting thermogenic function remains unknown. This study aims to identify phenolic acids that can enhance the thermogenic capacity of fat and investigate their roles and mechanisms in alleviating AS. Here, we utilized C3H10T1/2 cells and UCP1-luciferase gene knock-in mice to screen dietary phenolic acids, namely ferulic acid and protocatechuic acid, which could enhance the thermogenic capacity of the organism. Treating ApoE mice with these phenolic acids reduced aortic plaques and suppressed pro-inflammatory gene expression (, , ), while simultaneously promoting thermogenic functionality in interscapular brown adipose tissue and perivascular adipose tissue. Furthermore, applying conditioned media from brown adipose cells whose thermogenic capacity was activated by the phenolic acids to foam cells substantially inhibited the NLRP3-IL-1β inflammatory pathway and suppressed foam cell formation. These studies reveal that ferulic acid and protocatechuic acid can inhibit AS, at least in part, by upregulating UCP1 in adipose tissue, thereby suppressing the NLRP3-IL-1β inflammatory pathway and inhibiting foam cell formation in AS plaques. This validates the potential therapeutic function of phenolic acid compounds selected using UCP1 as a target for treating AS. Our work provides a theoretical basis for the precise utilization of food resources rich in phenolic acid compounds.
膳食酚酸可以通过增强脂肪组织的产热功能来对抗肥胖和非酒精性脂肪肝等代谢性疾病。解偶联蛋白1（UCP1）是一种关键的产热蛋白，与动脉粥样硬化（AS）的发展有关。膳食酚酸是否通过增强产热功能来抑制AS尚不清楚。本研究旨在鉴定能够增强脂肪产热能力的酚酸，并研究它们在减轻AS中的作用和机制。在这里，我们利用C3H10T1/2细胞和UCP1-荧光素酶基因敲入小鼠筛选膳食酚酸，即阿魏酸和原儿茶酸，它们可以增强机体的产热能力。用这些酚酸处理载脂蛋白E小鼠可减少主动脉斑块并抑制促炎基因表达（……），同时促进肩胛间棕色脂肪组织和血管周围脂肪组织的产热功能。此外，将由酚酸激活产热能力的棕色脂肪细胞的条件培养基应用于泡沫细胞，可显著抑制NLRP3-IL-1β炎症通路并抑制泡沫细胞形成。这些研究表明，阿魏酸和原儿茶酸可以至少部分地通过上调脂肪组织中的UCP1来抑制AS，从而抑制NLRP3-IL-1β炎症通路并抑制AS斑块中泡沫细胞的形成。这验证了以UCP1为靶点筛选的酚酸化合物在治疗AS方面的潜在治疗功能。我们的工作为精确利用富含酚酸化合物的食物资源提供了理论依据。
