{"title":"脂肪毒性:肥胖和耐力训练的悖论。","authors":"A P Russell","doi":"10.1038/sj.ijo.0802859","DOIUrl":null,"url":null,"abstract":"<p><p>The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IkappaB kinase (IKK)/NFkappaB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFalpha, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFalpha/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0802859","citationCount":"73","resultStr":"{\"title\":\"Lipotoxicity: the obese and endurance-trained paradox.\",\"authors\":\"A P Russell\",\"doi\":\"10.1038/sj.ijo.0802859\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IkappaB kinase (IKK)/NFkappaB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFalpha, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFalpha/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.</p>\",\"PeriodicalId\":14227,\"journal\":{\"name\":\"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2004-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1038/sj.ijo.0802859\",\"citationCount\":\"73\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/sj.ijo.0802859\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/sj.ijo.0802859","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Lipotoxicity: the obese and endurance-trained paradox.
The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IkappaB kinase (IKK)/NFkappaB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNFalpha, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNFalpha/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.