Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle.
<h4>Background</h4>The involvement of muscle triacylglycerol (TAG) storage in the onset of insulin resistance is questioned and the attention has shifted towards inhibition of insulin signalling by the lipid intermediate diacylglycerol (DAG). The enzyme 1,2-acylCoA:diacylglyceroltransfer...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/ad75f3a726a74f138354472eda7e5d3b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:ad75f3a726a74f138354472eda7e5d3b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:ad75f3a726a74f138354472eda7e5d3b2021-11-18T07:00:25ZParadoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle.1932-620310.1371/journal.pone.0014503https://doaj.org/article/ad75f3a726a74f138354472eda7e5d3b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21264296/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The involvement of muscle triacylglycerol (TAG) storage in the onset of insulin resistance is questioned and the attention has shifted towards inhibition of insulin signalling by the lipid intermediate diacylglycerol (DAG). The enzyme 1,2-acylCoA:diacylglyceroltransferase-1 (DGAT1) esterifies a fatty acyl-CoA on DAG to form TAG. Therefore, the aim of the present study was to investigate if unilateral overexpression of DGAT1 in adult rat Tibialis anterior (TA) muscle will increase conversion of the lipid intermediate DAG into TAG, thereby improving muscle insulin sensitivity.<h4>Methodology/principal findings</h4>The DGAT1 gene construct was injected in the left TA muscle of male rats on chow or high-fat (45% kcal) diet for three weeks, followed by application of one 800 V/cm and four 80 V/cm pulses, using the contralateral leg as sham-electroporated control. Seven days after electroporation, muscle specific insulin sensitivity was assessed with a hyperinsulinemic euglycemic clamp using 2-deoxy-[3H]glucose. Here, we provide evidence that unilateral overexpression of DGAT1 in TA muscle of male rats is associated with an increased rather than decreased DAG content. Strikingly, this increase in DAG content was accompanied by improved muscle insulin sensitivity. Interestingly, markers of muscle lipolysis and mitochondrial function were also increased in DGAT1 overexpressing muscle.<h4>Conclusions/significance</h4>We conclude that unilateral DGAT1 overexpression can rescue insulin sensitivity, possibly by increasing DAG and TAG turnover in skeletal muscle. In case of a proper balance between the supply and oxidation of fatty acids in skeletal muscle, the lipid intermediate DAG may not exert harmful effects on insulin signalling.Silvie TimmersJohan de Vogel-van den BoschMatthijs K C HesselinkDenis van BeurdenGert SchaartMaria Joao FerrazMario LosenPilar Martinez-MartinezMarc H De BaetsJohannes M F G AertsPatrick SchrauwenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e14503 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Silvie Timmers Johan de Vogel-van den Bosch Matthijs K C Hesselink Denis van Beurden Gert Schaart Maria Joao Ferraz Mario Losen Pilar Martinez-Martinez Marc H De Baets Johannes M F G Aerts Patrick Schrauwen Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| description |
<h4>Background</h4>The involvement of muscle triacylglycerol (TAG) storage in the onset of insulin resistance is questioned and the attention has shifted towards inhibition of insulin signalling by the lipid intermediate diacylglycerol (DAG). The enzyme 1,2-acylCoA:diacylglyceroltransferase-1 (DGAT1) esterifies a fatty acyl-CoA on DAG to form TAG. Therefore, the aim of the present study was to investigate if unilateral overexpression of DGAT1 in adult rat Tibialis anterior (TA) muscle will increase conversion of the lipid intermediate DAG into TAG, thereby improving muscle insulin sensitivity.<h4>Methodology/principal findings</h4>The DGAT1 gene construct was injected in the left TA muscle of male rats on chow or high-fat (45% kcal) diet for three weeks, followed by application of one 800 V/cm and four 80 V/cm pulses, using the contralateral leg as sham-electroporated control. Seven days after electroporation, muscle specific insulin sensitivity was assessed with a hyperinsulinemic euglycemic clamp using 2-deoxy-[3H]glucose. Here, we provide evidence that unilateral overexpression of DGAT1 in TA muscle of male rats is associated with an increased rather than decreased DAG content. Strikingly, this increase in DAG content was accompanied by improved muscle insulin sensitivity. Interestingly, markers of muscle lipolysis and mitochondrial function were also increased in DGAT1 overexpressing muscle.<h4>Conclusions/significance</h4>We conclude that unilateral DGAT1 overexpression can rescue insulin sensitivity, possibly by increasing DAG and TAG turnover in skeletal muscle. In case of a proper balance between the supply and oxidation of fatty acids in skeletal muscle, the lipid intermediate DAG may not exert harmful effects on insulin signalling. |
| format |
article |
| author |
Silvie Timmers Johan de Vogel-van den Bosch Matthijs K C Hesselink Denis van Beurden Gert Schaart Maria Joao Ferraz Mario Losen Pilar Martinez-Martinez Marc H De Baets Johannes M F G Aerts Patrick Schrauwen |
| author_facet |
Silvie Timmers Johan de Vogel-van den Bosch Matthijs K C Hesselink Denis van Beurden Gert Schaart Maria Joao Ferraz Mario Losen Pilar Martinez-Martinez Marc H De Baets Johannes M F G Aerts Patrick Schrauwen |
| author_sort |
Silvie Timmers |
| title |
Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| title_short |
Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| title_full |
Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| title_fullStr |
Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| title_full_unstemmed |
Paradoxical increase in TAG and DAG content parallel the insulin sensitizing effect of unilateral DGAT1 overexpression in rat skeletal muscle. |
| title_sort |
paradoxical increase in tag and dag content parallel the insulin sensitizing effect of unilateral dgat1 overexpression in rat skeletal muscle. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/ad75f3a726a74f138354472eda7e5d3b |
| work_keys_str_mv |
AT silvietimmers paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT johandevogelvandenbosch paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT matthijskchesselink paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT denisvanbeurden paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT gertschaart paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT mariajoaoferraz paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT mariolosen paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT pilarmartinezmartinez paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT marchdebaets paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT johannesmfgaerts paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle AT patrickschrauwen paradoxicalincreaseintaganddagcontentparalleltheinsulinsensitizingeffectofunilateraldgat1overexpressioninratskeletalmuscle |
| _version_ |
1718424063603376128 |