{"title":"以衰老小鼠的炎症解析信号为目标,通过饮食逆转肥胖饮食后的肝脏动态和微生物组的整合,进行靶向和非靶向脂质组学研究。","authors":"Gunjan Upadhyay , Siddabasave Gowda B. Gowda , Sidharth P. Mishra , Lipsa Rani Nath , Adewale James , Alisha Kulkarni , Yuktee Srikant , Rohitram Upendram , MathanKumar Marimuthu , Shu-Ping Hui , Shalini Jain , Kain Vasundhara , Hariom Yadav , Ganesh V. Halade","doi":"10.1016/j.bbalip.2024.159542","DOIUrl":null,"url":null,"abstract":"<div><p>Obesity, a global epidemic linked to around 4 million deaths yearly, arises from lifestyle imbalances impacting inflammation-related conditions like non-alcoholic fatty liver disease and gut dysbiosis. But the long-term effects of inflammation caused by lifestyle-related dietary changes remain unexplained. In this study, we used young male C57Bl/6 mice which were fed either an obesogenic diet (OBD) or a control diet (CON) for six months. Later, a group of mice from the OBD group were intervened to the CON diet (OBD-R) for four months, while another OBD group remained on the OBD diet. The OBD induced distinct changes in gut microbial, notably elevating Firmicutes and Actinobacteria, while reducing Bacteroidetes and Tenericutes. OBD-R restored microbial abundance like CON. Analyzing liver, plasma, and fecal samples revealed OBD-induced alterations in various structural and bioactive lipids, which were normalized to CON in the OBD-R, showcasing lipid metabolism flexibility and adaptability to dietary shifts. OBD increased omega 6 fatty acid, Arachidonic Acid (AA) and decreased omega 3-derived lipid mediators in the OBD mimicking non-alcoholic fatty liver disease thus impacting inflammation-resolution pathways. OBD also induced hepatic inflammation via increasing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and proinflammatory markers CCR2, TNF-α, and IL-1β in liver. Transitioning from OBD to CON mitigated inflammatory gene expression and restored lipid and cholesterol networks. This study underscores the intricate interplay between lifestyle-driven dietary changes, gut microbiota, lipid metabolism, and liver health. Notably, it suggests that shift from an OBD (omega-6 enriched) to CON partially alleviates signs of chronic inflammation during aging. Understanding these microbial, lipidomic, and hepatic inflammatory dynamics reveals potential therapeutic avenues for metabolic disorders induced by diet, emphasizing the pivotal role of diet in sustaining metabolic health.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. 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Analyzing liver, plasma, and fecal samples revealed OBD-induced alterations in various structural and bioactive lipids, which were normalized to CON in the OBD-R, showcasing lipid metabolism flexibility and adaptability to dietary shifts. OBD increased omega 6 fatty acid, Arachidonic Acid (AA) and decreased omega 3-derived lipid mediators in the OBD mimicking non-alcoholic fatty liver disease thus impacting inflammation-resolution pathways. OBD also induced hepatic inflammation via increasing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and proinflammatory markers CCR2, TNF-α, and IL-1β in liver. Transitioning from OBD to CON mitigated inflammatory gene expression and restored lipid and cholesterol networks. This study underscores the intricate interplay between lifestyle-driven dietary changes, gut microbiota, lipid metabolism, and liver health. 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引用次数: 0
摘要
肥胖症是一种全球性流行病,每年导致约 400 万人死亡,其原因是生活方式失衡影响了与炎症相关的疾病,如非酒精性脂肪肝和肠道菌群失调。但是,与生活方式相关的饮食变化所引起的炎症的长期影响仍未得到解释。在这项研究中,我们用年轻的雄性 C57Bl/6 小鼠喂食致肥饮食(OBD)或对照饮食(CON)六个月。之后,一组 OBD 组小鼠改用 CON 组饮食(OBD-R)四个月,另一组 OBD 组小鼠则继续食用 OBD 组饮食。OBD引起了肠道微生物的明显变化,尤其是增加了固着菌和放线菌,同时减少了类杆菌和韧皮部菌。OBD-R恢复了与CON相同的微生物丰度。对肝脏、血浆和粪便样本的分析表明,OBD 引起了各种结构脂质和生物活性脂质的改变,而在 OBD-R 中,这些改变与 CON 相同,这显示了脂质代谢的灵活性和对饮食变化的适应性。OBD增加了欧米伽6脂肪酸和花生四烯酸(AA),减少了欧米伽3衍生脂质介质,从而影响了炎症解决途径。OBD还通过增加丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)水平以及肝脏中的促炎症标志物CCR2、TNF-α和IL-1β诱导肝脏炎症。从 OBD 过渡到 CON 可减轻炎症基因的表达,并恢复脂质和胆固醇网络。这项研究强调了生活方式驱动的饮食变化、肠道微生物群、脂质代谢和肝脏健康之间错综复杂的相互作用。值得注意的是,它表明从 OBD(富含欧米茄-6)到 CON 的转变部分缓解了衰老过程中的慢性炎症迹象。了解这些微生物、脂质组和肝脏炎症的动态变化,可为饮食引起的代谢紊乱提供潜在的治疗途径,从而强调饮食在维持代谢健康中的关键作用。
Targeted and untargeted lipidomics with integration of liver dynamics and microbiome after dietary reversal of obesogenic diet targeting inflammation-resolution signaling in aging mice
Obesity, a global epidemic linked to around 4 million deaths yearly, arises from lifestyle imbalances impacting inflammation-related conditions like non-alcoholic fatty liver disease and gut dysbiosis. But the long-term effects of inflammation caused by lifestyle-related dietary changes remain unexplained. In this study, we used young male C57Bl/6 mice which were fed either an obesogenic diet (OBD) or a control diet (CON) for six months. Later, a group of mice from the OBD group were intervened to the CON diet (OBD-R) for four months, while another OBD group remained on the OBD diet. The OBD induced distinct changes in gut microbial, notably elevating Firmicutes and Actinobacteria, while reducing Bacteroidetes and Tenericutes. OBD-R restored microbial abundance like CON. Analyzing liver, plasma, and fecal samples revealed OBD-induced alterations in various structural and bioactive lipids, which were normalized to CON in the OBD-R, showcasing lipid metabolism flexibility and adaptability to dietary shifts. OBD increased omega 6 fatty acid, Arachidonic Acid (AA) and decreased omega 3-derived lipid mediators in the OBD mimicking non-alcoholic fatty liver disease thus impacting inflammation-resolution pathways. OBD also induced hepatic inflammation via increasing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and proinflammatory markers CCR2, TNF-α, and IL-1β in liver. Transitioning from OBD to CON mitigated inflammatory gene expression and restored lipid and cholesterol networks. This study underscores the intricate interplay between lifestyle-driven dietary changes, gut microbiota, lipid metabolism, and liver health. Notably, it suggests that shift from an OBD (omega-6 enriched) to CON partially alleviates signs of chronic inflammation during aging. Understanding these microbial, lipidomic, and hepatic inflammatory dynamics reveals potential therapeutic avenues for metabolic disorders induced by diet, emphasizing the pivotal role of diet in sustaining metabolic health.
期刊介绍:
BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.