The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance
Background/Aims: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particul...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-12-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/453174 |
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| author | Agnieszka U. Blachnio-Zabielska Marta Chacinska Mikkel H. Vendelbo Piotr Zabielski |
| author_facet | Agnieszka U. Blachnio-Zabielska Marta Chacinska Mikkel H. Vendelbo Piotr Zabielski |
| author_sort | Agnieszka U. Blachnio-Zabielska |
| collection | DOAJ |
| description | Background/Aims: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR. Methods: The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U13C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Results: HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG. Conclusion: The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats. |
| first_indexed | 2024-12-23T10:02:47Z |
| format | Article |
| id | doaj.art-5ee37a8f2edc4653996b0425adfb412a |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-23T10:02:47Z |
| publishDate | 2016-12-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-5ee37a8f2edc4653996b0425adfb412a2022-12-21T17:51:09ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-12-014051207122010.1159/000453174453174The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin ResistanceAgnieszka U. Blachnio-ZabielskaMarta ChacinskaMikkel H. VendelboPiotr ZabielskiBackground/Aims: Muscle bioactive lipids accumulation leads to several disorder states. The most common are insulin resistance (IR) and type 2 diabetes. There is an ongoing debate which of the lipid species plays the major role in induction of muscle IR. Our aim was to elucidate the role of particular lipid group in induction of muscle IR. Methods: The analyses were performed on muscle from the following groups of rats: 1. Control, fed standard diet, 2 HFD, fed high fat diet, 3. HFD/Myr, fed HFD and treated with myriocin (Myr), an inhibitor of ceramide de novo synthesis. We utilized [U13C] palmitate isotope tracer infusion and mass spectrometry to measure content and synthesis rate of muscle long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramide (Cer). Results: HFD led to intramuscular accumulation of LCACoA, DAG and Cer and skeletal muscle IR. Myr-treatment caused decrease in Cer (most noticeable for stearoyl-Cer and oleoyl-Cer) and accumulation of DAG, possibly due to re-channeling of excess of intramuscular LCACoA towards DAG synthesis. An improvement in insulin sensitivity at both systemic and muscular level coincided with decrease in ceramide, despite elevated intramuscular DAG. Conclusion: The improved insulin sensitivity was associated with decreased muscle stearoyl- and oleoyl-ceramide content. The results indicate that accumulation of those ceramide species has the greatest impact on skeletal muscle insulin sensitivity in rats.http://www.karger.com/Article/FullText/453174CeramideInsulin resistanceSkeletal muscle |
| spellingShingle | Agnieszka U. Blachnio-Zabielska Marta Chacinska Mikkel H. Vendelbo Piotr Zabielski The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance Cellular Physiology and Biochemistry Ceramide Insulin resistance Skeletal muscle |
| title | The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance |
| title_full | The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance |
| title_fullStr | The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance |
| title_full_unstemmed | The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance |
| title_short | The Crucial Role of C18-Cer in Fat-Induced Skeletal Muscle Insulin Resistance |
| title_sort | crucial role of c18 cer in fat induced skeletal muscle insulin resistance |
| topic | Ceramide Insulin resistance Skeletal muscle |
| url | http://www.karger.com/Article/FullText/453174 |
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