{"title":"更新的ANGPTL3-4-8模型作为甘油三酯在脂肪和氧化组织之间分配的机制","authors":"Ren Zhang, Kezhong Zhang","doi":"10.1016/j.plipres.2021.101140","DOIUrl":null,"url":null,"abstract":"<div><p>In mammals, triglyceride<span><span> (TG), the main form of lipids for storing and providing energy, is stored in white adipose tissue (WAT) after food intake, while during fasting it is routed to oxidative tissues (heart and skeletal muscle) for energy production, a process referred to as TG partitioning. </span>Lipoprotein lipase<span><span> (LPL), a rate-limiting enzyme in this fundamental </span>physiological process<span><span>, hydrolyzes circulating TG to generate </span>free fatty acids that are taken up by peripheral tissues. The postprandial activity of LPL declines in oxidative tissues but rises in WAT, directing TG to WAT; the reverse is true during fasting. However, the molecular mechanism in regulating tissue-specific LPL activity during the fed-fast cycle has not been completely understood. Research on angiopoietin-like (ANGPTL) proteins (A3, A4, and A8) has resulted in an ANGPTL3-4-8 model to explain the TG partitioning between WAT and oxidative tissues. Food intake induces A8 expression in the liver and WAT. Liver A8 activates A3 by forming the A3-8 complex, which is then secreted into the circulation. The A3-8 complex acts in an endocrine manner to inhibit LPL in oxidative tissues. WAT A8 forms the A4-8 complex, which acts locally to block A4's LPL-inhibiting activity. Therefore, the postprandial activity of LPL is low in oxidative tissues but high in WAT, directing circulating TG to WAT. Conversely, during fasting, reduced A8 expression in the liver and WAT disables A3 from inhibiting oxidative-tissue LPL and restores WAT A4's LPL-inhibiting activity, respectively. Thus, the fasting LPL activity is high in oxidative tissues but low in WAT, directing TG to the former. According to the model, we hypothesize that A8 antagonism has the potential to simultaneously reduce TG and increase HDL-cholesterol plasma levels. Future research on A3, A4, and A8 can hopefully provide more insights into human health, disease, and therapeutics.</span></span></span></p></div>","PeriodicalId":20650,"journal":{"name":"Progress in lipid research","volume":"85 ","pages":"Article 101140"},"PeriodicalIF":14.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"30","resultStr":"{\"title\":\"An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues\",\"authors\":\"Ren Zhang, Kezhong Zhang\",\"doi\":\"10.1016/j.plipres.2021.101140\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In mammals, triglyceride<span><span> (TG), the main form of lipids for storing and providing energy, is stored in white adipose tissue (WAT) after food intake, while during fasting it is routed to oxidative tissues (heart and skeletal muscle) for energy production, a process referred to as TG partitioning. </span>Lipoprotein lipase<span><span> (LPL), a rate-limiting enzyme in this fundamental </span>physiological process<span><span>, hydrolyzes circulating TG to generate </span>free fatty acids that are taken up by peripheral tissues. The postprandial activity of LPL declines in oxidative tissues but rises in WAT, directing TG to WAT; the reverse is true during fasting. However, the molecular mechanism in regulating tissue-specific LPL activity during the fed-fast cycle has not been completely understood. Research on angiopoietin-like (ANGPTL) proteins (A3, A4, and A8) has resulted in an ANGPTL3-4-8 model to explain the TG partitioning between WAT and oxidative tissues. Food intake induces A8 expression in the liver and WAT. Liver A8 activates A3 by forming the A3-8 complex, which is then secreted into the circulation. The A3-8 complex acts in an endocrine manner to inhibit LPL in oxidative tissues. WAT A8 forms the A4-8 complex, which acts locally to block A4's LPL-inhibiting activity. Therefore, the postprandial activity of LPL is low in oxidative tissues but high in WAT, directing circulating TG to WAT. Conversely, during fasting, reduced A8 expression in the liver and WAT disables A3 from inhibiting oxidative-tissue LPL and restores WAT A4's LPL-inhibiting activity, respectively. Thus, the fasting LPL activity is high in oxidative tissues but low in WAT, directing TG to the former. According to the model, we hypothesize that A8 antagonism has the potential to simultaneously reduce TG and increase HDL-cholesterol plasma levels. Future research on A3, A4, and A8 can hopefully provide more insights into human health, disease, and therapeutics.</span></span></span></p></div>\",\"PeriodicalId\":20650,\"journal\":{\"name\":\"Progress in lipid research\",\"volume\":\"85 \",\"pages\":\"Article 101140\"},\"PeriodicalIF\":14.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"30\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in lipid research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0163782721000564\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in lipid research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163782721000564","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues
In mammals, triglyceride (TG), the main form of lipids for storing and providing energy, is stored in white adipose tissue (WAT) after food intake, while during fasting it is routed to oxidative tissues (heart and skeletal muscle) for energy production, a process referred to as TG partitioning. Lipoprotein lipase (LPL), a rate-limiting enzyme in this fundamental physiological process, hydrolyzes circulating TG to generate free fatty acids that are taken up by peripheral tissues. The postprandial activity of LPL declines in oxidative tissues but rises in WAT, directing TG to WAT; the reverse is true during fasting. However, the molecular mechanism in regulating tissue-specific LPL activity during the fed-fast cycle has not been completely understood. Research on angiopoietin-like (ANGPTL) proteins (A3, A4, and A8) has resulted in an ANGPTL3-4-8 model to explain the TG partitioning between WAT and oxidative tissues. Food intake induces A8 expression in the liver and WAT. Liver A8 activates A3 by forming the A3-8 complex, which is then secreted into the circulation. The A3-8 complex acts in an endocrine manner to inhibit LPL in oxidative tissues. WAT A8 forms the A4-8 complex, which acts locally to block A4's LPL-inhibiting activity. Therefore, the postprandial activity of LPL is low in oxidative tissues but high in WAT, directing circulating TG to WAT. Conversely, during fasting, reduced A8 expression in the liver and WAT disables A3 from inhibiting oxidative-tissue LPL and restores WAT A4's LPL-inhibiting activity, respectively. Thus, the fasting LPL activity is high in oxidative tissues but low in WAT, directing TG to the former. According to the model, we hypothesize that A8 antagonism has the potential to simultaneously reduce TG and increase HDL-cholesterol plasma levels. Future research on A3, A4, and A8 can hopefully provide more insights into human health, disease, and therapeutics.
期刊介绍:
The significance of lipids as a fundamental category of biological compounds has been widely acknowledged. The utilization of our understanding in the fields of biochemistry, chemistry, and physiology of lipids has continued to grow in biotechnology, the fats and oils industry, and medicine. Moreover, new aspects such as lipid biophysics, particularly related to membranes and lipoproteins, as well as basic research and applications of liposomes, have emerged. To keep up with these advancements, there is a need for a journal that can evaluate recent progress in specific areas and provide a historical perspective on current research. Progress in Lipid Research serves this purpose.