Table_2_Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype.xlsx

IntroductionObesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism.MethodsIn the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation.ResultsAllicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in the mean aspect ratio of mitochondria in allicin-treated cells indicate a shift in mitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1).DiscussionTranscriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings.

肥胖是一种重大的健康问题，因其与心血管疾病、糖尿病、高血压以及某些癌症的高发风险相关。预防或减少肥胖的策略主要集中于可能诱导棕色脂肪细胞表型，使其能够以热能形式释放能量的天然化合物的作用。大蒜的生物活性成分蒜素，以其多种药理功能而闻名，已知能刺激能量代谢。本研究通过量化脂滴（LDs）和线粒体动态，以及分化六天后转录组的变化，探讨了蒜素对人类辛普森-高拉比-贝赫尔综合征（SGBS）细胞的影响。结果表明，蒜素显著促进了脂滴表面积和尺寸的减少，导致多室脂肪细胞的形成，这一结果通过上调与脂肪分解相关的基因得到证实。蒜素处理细胞中线粒体数量增加和平均长宽比降低表明线粒体动力学向分裂方向转变。结构结果通过转录组分析得到证实，显示与棕色脂肪细胞相关的基因表达显著排列，特别是T-box转录因子1（TBX1）、解偶联蛋白1（UCP1）、PPARG共激活剂1α（PPARGC1A）、过氧化物酶体增殖物激活受体α（PPARA）和氧化磷酸化相关基因的表达增加。最有希望的目标是核基因，如视黄酸X受体α（RXRA）、视黄酸X受体γ（RXRG）、核受体超家族1组H成员3（NR1H3）、核受体超家族1组H成员4（NR1H4）、PPARA和雌性受体1（ESR1）。转录组数据和基于网络药理学的分析方法揭示了蒜素的基因和潜在靶点涉及配体激活转录因子活性、细胞内受体信号传导、调节寒冷诱导产热以及脂质代谢的正向调节。本研究突出了蒜素通过影响脂滴动态、线粒体形态和棕色标记基因的表达，触发人类SGBS细胞棕色化的潜在作用。通过理解蒜素促进这种作用的潜在靶点，可能揭示潜在的信号通路并支持这些发现。