Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria; Laboratory of Metabolomics, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria.
Department of Plant Cell Biotechnology, Center of Plant Systems Biology and Biotechnology, 4000 Plovdiv, Bulgaria; Laboratory of Metabolomics, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd., 4000 Plovdiv, Bulgaria; Department of Plant Physiology and Molecular Biology, University of Plovdiv, 24 Tzar Assen Str., 4000 Plovdiv, Bulgaria.
Biomed Pharmacother. 2022 Dec;156:113862. doi: 10.1016/j.biopha.2022.113862. Epub 2022 Oct 12.
Obesity is an ingrained health problem with а multifactorial origin and а long history, thereby innovations in the treatment strategies are of great importance. In the search of a remedy for excessive weight gain, we have directed our investigations to phytochemicals as valuable bioactive compounds. Betulinic acid (BA), among the other triterpenoids, is known for its anti-inflammatory and anti-neoplastic properties. In addition, a previous study of ours has demonstrated а potent anti-adipogenic effect of BA in human adipocytes. Therefore, we aimed here to further verify the anti-obesogenic effect of BA in vivo in Caenorhabditis elegans. Induction of lipid accumulation in the nematodes was modelled with glucose-supplemented media, followed by treatment with BA (10-50 μM) or orlistat (12 μM) as a control anti-obesity medication. Oil red O and Nile red staining were applied to provide quantification of accumulated lipids. Analysis of the relative expression of genes, related to lipid metabolism suggested molecular mechanism of lipid-reducing action of BA in C. elegans. Treatment of nematodes with BA significantly decreased the lipid accumulation, downregulated desaturases involved in lipogenesis (fat-5, fat-6 and fat-7), modulated key transcription factors (nhr-49 and hlh-11) and microRNAs (miR-60, lin-4, let-7 and miR-786) associated with the lipid metabolism. Collectively, the current research provides additional insight on the molecular mechanism of the BA's anti-obesogenic effect in vivo. Furthermore, it validates the potential of BA as a candidate compound in obesity management by reducing lipid accumulation.
肥胖是一种根深蒂固的健康问题，具有多因素起源和悠久的历史，因此治疗策略的创新非常重要。在寻找治疗体重过度增加的方法时，我们将研究方向转向了植物化学物质，这些物质是有价值的生物活性化合物。白桦脂酸 (BA) 是三萜类化合物之一，以其抗炎和抗肿瘤特性而闻名。此外，我们之前的一项研究表明 BA 对人脂肪细胞具有强烈的抗脂肪生成作用。因此，我们旨在进一步验证 BA 在秀丽隐杆线虫体内的抗肥胖作用。通过添加葡萄糖的培养基诱导线虫中的脂质积累，然后用 BA（10-50 μM）或奥利司他（12 μM）处理，作为对照抗肥胖药物。应用油红 O 和尼罗红染色来定量积累的脂质。分析与脂质代谢相关的基因的相对表达，提示了 BA 在 C. elegans 中减少脂质的分子机制。BA 处理线虫可显著减少脂质积累，下调参与脂肪生成的去饱和酶（fat-5、fat-6 和 fat-7），调节关键转录因子（nhr-49 和 hlh-11）和与脂质代谢相关的 microRNAs（miR-60、lin-4、let-7 和 miR-786）。总的来说，目前的研究为 BA 在体内的抗肥胖作用的分子机制提供了更多的见解。此外，它验证了 BA 作为候选化合物通过减少脂质积累来管理肥胖症的潜力。
