Lipid accumulation in non-adipose tissue and lipotoxicity
Abstract Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and...
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Veröffentlicht in: | Physiology & behavior 2008-05, Vol.94 (2), p.231-241 |
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description | Abstract Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. Initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart. |
doi_str_mv | 10.1016/j.physbeh.2007.11.049 |
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Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. Initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart.</description><identifier>ISSN: 0031-9384</identifier><identifier>EISSN: 1873-507X</identifier><identifier>DOI: 10.1016/j.physbeh.2007.11.049</identifier><identifier>PMID: 18222498</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Ectopic fat ; Humans ; Lipid accumulation ; Lipid Metabolism - physiology ; Lipids - toxicity ; Lipotoxicity ; Liver - metabolism ; Muscle, Skeletal - metabolism ; Myocardium - metabolism ; Non-adipose tissue ; Obesity - metabolism ; Obesity - physiopathology ; Pancreas - metabolism ; Psychiatry</subject><ispartof>Physiology & behavior, 2008-05, Vol.94 (2), p.231-241</ispartof><rights>Elsevier Inc.</rights><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-4116c29142b6897802aaecd6ff4633dbe08bb7458853bd98618dc258123199b83</citedby><cites>FETCH-LOGICAL-c562t-4116c29142b6897802aaecd6ff4633dbe08bb7458853bd98618dc258123199b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.physbeh.2007.11.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18222498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Herpen, N.A</creatorcontrib><creatorcontrib>Schrauwen-Hinderling, V.B</creatorcontrib><title>Lipid accumulation in non-adipose tissue and lipotoxicity</title><title>Physiology & behavior</title><addtitle>Physiol Behav</addtitle><description>Abstract Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. Initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart.</description><subject>Animals</subject><subject>Ectopic fat</subject><subject>Humans</subject><subject>Lipid accumulation</subject><subject>Lipid Metabolism - physiology</subject><subject>Lipids - toxicity</subject><subject>Lipotoxicity</subject><subject>Liver - metabolism</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Myocardium - metabolism</subject><subject>Non-adipose tissue</subject><subject>Obesity - metabolism</subject><subject>Obesity - physiopathology</subject><subject>Pancreas - metabolism</subject><subject>Psychiatry</subject><issn>0031-9384</issn><issn>1873-507X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUGLFDEQhYMo7rj6E5Q-eeu2Kkl3JxdFll0VBjy4C95COqlhM_YkbadbnH9vhhkQvFiXguLVe9RXjL1GaBCwe7dvpsdjHuix4QB9g9iA1E_YBlUv6hb670_ZBkBgrYWSV-xFznsoJaR4zq5Qcc6lVhumt2EKvrLOrYd1tEtIsQqxiinW1ocpZaqWkPNKlY2-GstkSb-DC8vxJXu2s2OmV5d-zR7ubu9vPtfbr5--3Hzc1q7t-FJLxM5xjZIPndK9Am4tOd_tdrITwg8Eahh62SrVisFr1aHyjrcKuUCtByWu2duz7zSnnyvlxRxCdjSONlJas8FyYIdtX4TtWejmlPNMOzPN4WDno0EwJ2Zmby7MzImZQTSFWdl7cwlYhwP5v1sXSEXw4SygcuavQLPJLlB05MNMbjE-hf9GvP_HwY0hBmfHH3SkvE_rHAtDgyZzA-bb6XGnv0EPIBW04g-XsJQC</recordid><startdate>20080523</startdate><enddate>20080523</enddate><creator>van Herpen, N.A</creator><creator>Schrauwen-Hinderling, V.B</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7TK</scope></search><sort><creationdate>20080523</creationdate><title>Lipid accumulation in non-adipose tissue and lipotoxicity</title><author>van Herpen, N.A ; Schrauwen-Hinderling, V.B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-4116c29142b6897802aaecd6ff4633dbe08bb7458853bd98618dc258123199b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Ectopic fat</topic><topic>Humans</topic><topic>Lipid accumulation</topic><topic>Lipid Metabolism - physiology</topic><topic>Lipids - toxicity</topic><topic>Lipotoxicity</topic><topic>Liver - metabolism</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Myocardium - metabolism</topic><topic>Non-adipose tissue</topic><topic>Obesity - metabolism</topic><topic>Obesity - physiopathology</topic><topic>Pancreas - metabolism</topic><topic>Psychiatry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Herpen, N.A</creatorcontrib><creatorcontrib>Schrauwen-Hinderling, V.B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Physiology & behavior</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Herpen, N.A</au><au>Schrauwen-Hinderling, V.B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipid accumulation in non-adipose tissue and lipotoxicity</atitle><jtitle>Physiology & behavior</jtitle><addtitle>Physiol Behav</addtitle><date>2008-05-23</date><risdate>2008</risdate><volume>94</volume><issue>2</issue><spage>231</spage><epage>241</epage><pages>231-241</pages><issn>0031-9384</issn><eissn>1873-507X</eissn><abstract>Abstract Obesity is a well-known risk factor for the development of type 2 diabetes mellitus and cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue, but also in non-adipose tissues. The latter is also known as ectopic lipid accumulation and may be a possible link between obesity and its comorbidities such as insulin resistance, type 2 diabetes mellitus and cardiovascular disease. In skeletal muscle and liver, lipid accumulation has been associated with the development of insulin resistance, an early hallmark of developing type 2 diabetes mellitus. More specifically, accumulation of intermediates of lipid metabolism, such as diacylglycerol (DAG) and Acyl-CoA have been shown to interfere with insulin signaling in these tissues. Initially, muscular and hepatic insulin resistance can be overcome by an increased insulin production by the pancreas, resulting in hyperinsulinemia. However, during the progression towards overt type 2 diabetes, pancreatic failure occurs resulting in reduced insulin production. Interestingly, also in the pancreas lipid accumulation has been shown to precede dysfunction. Finally, accumulation of fat in the heart has been associated with cardiac dysfunction and heart failure, which may be an explanation for diabetic cardiomyopathy. Taken together, we conclude that evidence for deleterious effects of lipid accumulation in non-adipose tissue (lipotoxicity) is strong. However, while ample human data is available for skeletal muscle and the liver, future research should focus on lipid accumulation in the pancreas and the heart.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18222498</pmid><doi>10.1016/j.physbeh.2007.11.049</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Ectopic fat Humans Lipid accumulation Lipid Metabolism - physiology Lipids - toxicity Lipotoxicity Liver - metabolism Muscle, Skeletal - metabolism Myocardium - metabolism Non-adipose tissue Obesity - metabolism Obesity - physiopathology Pancreas - metabolism Psychiatry |
title | Lipid accumulation in non-adipose tissue and lipotoxicity |
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