PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression
Background. Type 2 diabetes is characterized by reduced insulin sensitivity, elevated blood metabolites, and reduced mitochondrial metabolism with reduced expression of genes governing metabolism such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α regulates...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2023/4779199 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832547348692074496 |
|---|---|
| author | Caroline N. Rivera Jason S. Hinkle Rachel M. Watne Trent C. Macgowan Andrew J. Wommack Roger A. Vaughan |
| author_facet | Caroline N. Rivera Jason S. Hinkle Rachel M. Watne Trent C. Macgowan Andrew J. Wommack Roger A. Vaughan |
| author_sort | Caroline N. Rivera |
| collection | DOAJ |
| description | Background. Type 2 diabetes is characterized by reduced insulin sensitivity, elevated blood metabolites, and reduced mitochondrial metabolism with reduced expression of genes governing metabolism such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α regulates the expression of branched-chain amino acid (BCAA) metabolism, and thus, increased circulating BCAA in diabetics may be partially explained by reduced PGC-1α expression. PGC-1α functions in-part through interactions with peroxisome proliferator-activated receptor β/δ (PPARβ/δ). The present report examined the effects of the PPARβ/δ agonism on cell metabolism and related gene/protein expression of cultured myotubes, with a primary emphasis on determining the effects of GW on BCAA disposal and catabolic enzyme expression. Methods. C2C12 myotubes were treated with GW501516 (GW) for up to 24 hours. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Metabolic gene and protein expression were assessed via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Media BCAA content was assessed via liquid chromatography–mass spectrometry (LC/MS). Results. GW significantly increased PGC-1α protein expression, mitochondrial content, and mitochondrial function. GW also significantly reduced BCAA content within culture media following 24-hour treatment; however, expression of BCAA catabolic enzymes/transporter was unchanged. Conclusion. These data confirm the ability of GW to increase muscle PGC-1α content and decrease BCAA media content without affecting BCAA catabolic enzymes/transporter. These findings suggest heightened BCAA uptake (and possibly metabolism) may occur without substantial changes in the protein levels of related cell machinery. |
| format | Article |
| id | doaj-art-3e669f0f6ce446588f716d863f1f8c5d |
| institution | Kabale University |
| issn | 1687-4765 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-3e669f0f6ce446588f716d863f1f8c5d2025-02-03T06:45:02ZengWileyPPAR Research1687-47652023-01-01202310.1155/2023/4779199PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme ExpressionCaroline N. Rivera0Jason S. Hinkle1Rachel M. Watne2Trent C. Macgowan3Andrew J. Wommack4Roger A. Vaughan5Department of Exercise ScienceDepartment of Exercise ScienceDepartment of ChemistryDepartment of ChemistryDepartment of ChemistryDepartment of Exercise ScienceBackground. Type 2 diabetes is characterized by reduced insulin sensitivity, elevated blood metabolites, and reduced mitochondrial metabolism with reduced expression of genes governing metabolism such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α regulates the expression of branched-chain amino acid (BCAA) metabolism, and thus, increased circulating BCAA in diabetics may be partially explained by reduced PGC-1α expression. PGC-1α functions in-part through interactions with peroxisome proliferator-activated receptor β/δ (PPARβ/δ). The present report examined the effects of the PPARβ/δ agonism on cell metabolism and related gene/protein expression of cultured myotubes, with a primary emphasis on determining the effects of GW on BCAA disposal and catabolic enzyme expression. Methods. C2C12 myotubes were treated with GW501516 (GW) for up to 24 hours. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Metabolic gene and protein expression were assessed via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Media BCAA content was assessed via liquid chromatography–mass spectrometry (LC/MS). Results. GW significantly increased PGC-1α protein expression, mitochondrial content, and mitochondrial function. GW also significantly reduced BCAA content within culture media following 24-hour treatment; however, expression of BCAA catabolic enzymes/transporter was unchanged. Conclusion. These data confirm the ability of GW to increase muscle PGC-1α content and decrease BCAA media content without affecting BCAA catabolic enzymes/transporter. These findings suggest heightened BCAA uptake (and possibly metabolism) may occur without substantial changes in the protein levels of related cell machinery.http://dx.doi.org/10.1155/2023/4779199 |
| spellingShingle | Caroline N. Rivera Jason S. Hinkle Rachel M. Watne Trent C. Macgowan Andrew J. Wommack Roger A. Vaughan PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression PPAR Research |
| title | PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression |
| title_full | PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression |
| title_fullStr | PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression |
| title_full_unstemmed | PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression |
| title_short | PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression |
| title_sort | pparβ δ agonism with gw501516 increases myotube pgc 1α content and reduces bcaa media content independent of changes in bcaa catabolic enzyme expression |
| url | http://dx.doi.org/10.1155/2023/4779199 |
| work_keys_str_mv | AT carolinenrivera pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression AT jasonshinkle pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression AT rachelmwatne pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression AT trentcmacgowan pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression AT andrewjwommack pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression AT rogeravaughan pparbdagonismwithgw501516increasesmyotubepgc1acontentandreducesbcaamediacontentindependentofchangesinbcaacatabolicenzymeexpression |