Department of Earth, Environmental, and Life Sciences (DISTAV), University of Genoa, Corso Europa 26, 16132 Genoa, Italy.
Inter-University Center for the Promotion of the 3Rs Principles in Teaching & Research (Centro 3R), 56122 Pisa, Italy.
Molecules. 2022 Nov 1;27(21):7417. doi: 10.3390/molecules27217417.
Many different amphibian skin peptides have been characterized and proven to exert various biological actions, such as wound-healing, immunomodulatory, anti-oxidant, anti-inflammatory and anti-diabetic effects. In this work, the possible anti-steatotic effect of macrotympanain A1 (MA1) (FLPGLECVW), a skin peptide isolated from the Chinese odorous frog , was investigated. We used a well-established in vitro model of hepatic steatosis, consisting of lipid-loaded rat hepatoma FaO cells. In this model, a 24 h treatment with 10 µg/mL MA1 exerted a significant anti-steatotic action, being able to reduce intracellular triglyceride content. Accordingly, the number and diameter of cytosolic lipid droplets (LDs) were reduced by peptide treatment. The expression of key genes of hepatic lipid metabolism, such as PPARs and PLINs, was measured by real-time qPCR. MA1 counteracted the fatty acid-induced upregulation of PPARγ expression and increased PLIN3 expression, suggesting a role in promoting lipophagy. The present data demonstrate for the first time a direct anti-steatotic effect of a peptide from amphibian skin secretion and pave the way to further studies on the use of amphibian peptides for beneficial actions against metabolic diseases.
许多不同的两栖动物皮肤肽已被鉴定并证明具有多种生物学作用,如伤口愈合、免疫调节、抗氧化、抗炎和抗糖尿病作用。在这项工作中,研究了从中国臭蛙中分离出来的皮肤肽宏蛋白 A1(MA1)(FLPGLECVW)的可能抗脂肪变性作用。我们使用了由负载脂质的大鼠肝癌 FaO 细胞组成的成熟体外肝脂肪变性模型。在该模型中,10μg/ml MA1 处理 24 小时可发挥显著的抗脂肪变性作用,能够降低细胞内甘油三酯含量。因此,肽处理减少了细胞质脂滴(LDs)的数量和直径。通过实时 qPCR 测量肝脂质代谢的关键基因,如 PPARs 和 PLINs 的表达。MA1 拮抗脂肪酸诱导的 PPARγ 表达上调,并增加 PLIN3 的表达,提示其在促进脂自噬中的作用。本研究首次证明了来自两栖动物皮肤分泌物的肽具有直接的抗脂肪变性作用,为进一步研究利用两栖动物肽对抗代谢疾病的有益作用铺平了道路。