副干酪乳酪杆菌CCFM1224后生元通过调节脂质代谢缓解皮脂代谢紊乱

Lacticaseibacillus paracasei CCFM1224 postbiotics alleviate sebum metabolism disorders by regulating lipid metabolism

摘要:

目的 皮脂代谢紊乱是多种皮肤疾病的重要诱因，后生元作为一种新兴的微生态制剂显示出调控代谢的潜力。本研究旨在探究副干酪乳酪杆菌CCFM1224后生元对皮脂代谢紊乱的改善作用及其机制，并进一步探索后生元起效组分。方法 通过构建油酸诱导的小鼠皮脂代谢紊乱模型，从表观指标、激素指标、皮肤脂质含量水平综合评价CCFM1224后生元对皮脂紊乱的改善效果，并检测皮肤脂质代谢相关基因表达变化。利用游离脂肪酸诱导的HepG2细胞脂质堆积模型对后生元功效组分进行筛选。结果 CCFM1224后生元能显著缓解小鼠皮脂代谢紊乱导致的体重异常增长与睾丸系数增大，减轻皮肤组织病理损伤，降低炎症因子IL-6、IL-1β和TNF-α水平，并下调皮肤组织中甘油三酯(triglyceride, TG)及游离脂肪酸(non-esterified fatty acid, NEFA)含量。机制研究表明，CCFM1224后生元通过抑制脂质合成基因(FASN、PPAR-γ、SREBP-1c)的表达，促进脂质分解基因(PPAR-α、HSL、ATGL)的表达，从而调节皮脂代谢。细胞实验表明，CCFM1224后生元灭活菌体成分能够显著减轻细胞脂质积累及相关损伤，说明其为CCFM1224后生元发挥功效的主要活性组分。结论 副干酪乳酪杆菌CCFM1224能够通过调节激素分泌以及脂质代谢途径缓解皮脂代谢紊乱，其关键功效物质为灭活菌体组分而非发酵上清液。本研究为后生元在脂质代谢紊乱调控中的应用提供了理论依据，也为相关功能性微生物制剂的开发奠定了研究基础。

Abstract:

Objective Sebum metabolism disorders are a key contributing factor to various dermatological conditions. As an emerging class of microbial agents, postbiotics show potential in regulating metabolic processes. This study aimed to investigate the efficacy and mechanisms of Lacticaseibacillus paracasei CCFM1224 postbiotics in alleviating sebum metabolism disorders and explore the active components responsible for the effects.Methods Using a mouse model of oleic acid-induced sebum metabolism disorders, we comprehensively evaluated the efficacy of CCFM1224 postbiotics in ameliorating sebum imbalance. This evaluation encompassed phenotypic measurements, hormonal parameters, and skin lipid content. Changes in the expression of genes related to skin lipid metabolism were measured via real-time quantitative PCR. Subsequently, a free fatty acid-induced lipid accumulation model in HepG2 cells was utilized to screen the active components of postbiotics.Results CCFM1224 postbiotics significantly ameliorated sebum metabolism disorders in mice. This was evidenced by mitigated abnormal weight gain, a reduced testicle index, alleviated histopathological skin damage, and decreased levels of inflammatory cytokines (IL-6, IL-1β, and TNF-α) as well as triglyceride (TG) and non-esterified fatty acid (NEFA) in the skin tissue. CCFM1224 postbiotics modulated sebum metabolism by downregulating the expression of lipogenesis-related genes (FASN, PPAR-γ, and SREBP-1c) and upregulating the expression of lipolysis-related genes (PPAR-α, HSL, and ATGL). Further cellular validation identified the inactivated bacterial cell component as the key functional fraction, which effectively alleviated intracellular lipid accumulation and associated damage, thereby clarifying the material basis for the effects of CCFM1224 postbiotics.Conclusion L. paracasei CCFM1224 ameliorate sebum metabolism disorders by modulating hormone secretion and lipid metabolic pathways. The key bioactive components were identified as the inactivated bacterial cells, rather than the fermentation supernatant. This finding provides a theoretical foundation for the application of postbiotics in regulating lipid metabolism disorders and establishes a basis for developing related functional microbial preparations.