High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism
Peroxisome Proliferator Activated Receptor (PPAR)-δ agonists may serve for treating metabolic diseases. However, the effects of PPAR-δ agonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways a...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/509502 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850175284594081792 |
|---|---|
| author | Elisa Benetti Raffaella Mastrocola Mara Rogazzo Fausto Chiazza Manuela Aragno Roberto Fantozzi Massimo Collino Marco A. Minetto |
| author_facet | Elisa Benetti Raffaella Mastrocola Mara Rogazzo Fausto Chiazza Manuela Aragno Roberto Fantozzi Massimo Collino Marco A. Minetto |
| author_sort | Elisa Benetti |
| collection | DOAJ |
| description | Peroxisome Proliferator Activated Receptor (PPAR)-δ agonists may serve for treating metabolic diseases. However, the effects of PPAR-δ agonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δ agonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δ upregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δ activation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades. |
| format | Article |
| id | doaj-art-ce99c4e2dade413284250b8288ecbbb2 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-ce99c4e2dade413284250b8288ecbbb22025-08-20T02:19:30ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/509502509502High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ AgonismElisa Benetti0Raffaella Mastrocola1Mara Rogazzo2Fausto Chiazza3Manuela Aragno4Roberto Fantozzi5Massimo Collino6Marco A. Minetto7Department of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125 Torino, ItalyDepartment of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, ItalyDepartment of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10125 Torino, ItalyDepartment of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, ItalyDepartment of Drug Science and Technology, University of Turin, Via Giuria 9, 10125 Torino, ItalyDivision of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, ItalyPeroxisome Proliferator Activated Receptor (PPAR)-δ agonists may serve for treating metabolic diseases. However, the effects of PPAR-δ agonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δ agonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δ upregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δ activation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.http://dx.doi.org/10.1155/2013/509502 |
| spellingShingle | Elisa Benetti Raffaella Mastrocola Mara Rogazzo Fausto Chiazza Manuela Aragno Roberto Fantozzi Massimo Collino Marco A. Minetto High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism Mediators of Inflammation |
| title | High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism |
| title_full | High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism |
| title_fullStr | High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism |
| title_full_unstemmed | High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism |
| title_short | High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism |
| title_sort | high sugar intake and development of skeletal muscle insulin resistance and inflammation in mice a protective role for ppar δ agonism |
| url | http://dx.doi.org/10.1155/2013/509502 |
| work_keys_str_mv | AT elisabenetti highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT raffaellamastrocola highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT mararogazzo highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT faustochiazza highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT manuelaaragno highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT robertofantozzi highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT massimocollino highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism AT marcoaminetto highsugarintakeanddevelopmentofskeletalmuscleinsulinresistanceandinflammationinmiceaprotectiveroleforppardagonism |