Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
Front Cell Infect Microbiol. 2024 Jan 8;13:1285584. doi: 10.3389/fcimb.2023.1285584. eCollection 2023.
Obesity is an inducible factor for the cause of chronic diseases and is described by an increase in the size and number of adipocytes that differentiate from precursor cells (preadipocytes). Parasitic helminths are the strongest natural trigger of type 2 immune system, and several studies have showed that helminth infections are inversely correlated with metabolic syndromes.
METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether helminth-derived molecules have therapeutic effects on high-fat diet (HFD)-induced obesity, we isolated total lysates from muscle larvae. We then checked the anti-obesity effect after intraperitoneal administration and intraoral administration of total lysate from muscle larvae in a diet-induced obesity model. total lysates protect against obesity by inhibiting the proinflammatory response and/or enhancing M2 macrophages. In addition, we determined the effects of total lysates from muscle larvae on anti-obesity activities in 3T3-L1 preadipocytes by investigating the expression levels of key adipogenic regulators, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding protein alpha (C/EBPα) and adipocyte protein 2 (aP2). Oil Red O staining showed that the total lysates from muscle larvae decreased the differentiation of 3T3-L1 preadipocytes by decreasing the number of lipid droplets. In addition, the production levels of proinflammatory cytokines IL-1β, IL-6, IFN-γ and TNF-α were examined by enzyme-linked immunosorbent assay (ELISA). total lysates decreased intracellular lipid accumulation and suppressed the expression levels of PPARγ, C/EBPα and aP2.
CONCLUSION/SIGNIFICANCE: These results show that total lysate significantly suppresses the symptoms of obesity in a diet- induced obesity model and 3T3-L1 cell differentiation and suggest that it has potential for novel anti-obesity therapeutics.
肥胖是导致慢性病的一个诱发性因素，其特征是脂肪细胞的大小和数量增加，这些脂肪细胞是由前体细胞（前脂肪细胞）分化而来的。寄生虫蠕虫是最强的 2 型免疫系统天然触发物，有几项研究表明，蠕虫感染与代谢综合征呈负相关。
方法/主要发现：为了研究蠕虫来源的分子是否对高脂肪饮食（HFD）诱导的肥胖具有治疗作用，我们从肌肉幼虫中分离了总裂解物。然后，我们检查了肌肉幼虫总裂解物经腹腔内给药和口服给药后在饮食诱导肥胖模型中的抗肥胖作用。肌肉幼虫的总裂解物通过抑制促炎反应和/或增强 M2 巨噬细胞来预防肥胖。此外，我们通过研究关键脂肪生成调节剂（包括过氧化物酶体增殖物激活受体γ（PPARγ）、CCAAT 增强子结合蛋白α（C/EBPα）和脂肪细胞蛋白 2（aP2））的表达水平，确定了肌肉幼虫总裂解物对 3T3-L1 前脂肪细胞抗肥胖活性的影响。油红 O 染色显示，肌肉幼虫的总裂解物通过减少脂滴数量来减少 3T3-L1 前脂肪细胞的分化。此外，通过酶联免疫吸附试验（ELISA）检测促炎细胞因子 IL-1β、IL-6、IFN-γ和 TNF-α的产生水平。肌肉幼虫的总裂解物减少了细胞内脂质积累，并抑制了 PPARγ、C/EBPα和 aP2 的表达水平。
结论/意义：这些结果表明，肌肉幼虫的总裂解物显著抑制了饮食诱导肥胖模型中的肥胖症状和 3T3-L1 细胞分化，并表明其具有作为新型抗肥胖治疗药物的潜力。
