Difference between revisions of "Hoeks 2012 J Cell Physiol"
| (13 intermediate revisions by 5 users not shown) | |||
| Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P ( | |title=Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) Enhanced lipid -but not carbohydrate- supported mitochondrial respiration in skeletal muscle of PGC-1α overexpressing mice. J Cell Physiol 227:1026-33. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/21520076 PMID:21520076] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/21520076 PMID: 21520076] | ||
|authors=Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P | |authors=Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P | ||
|year= | |year=2012 | ||
|journal=J Cell Physiol | |journal=J Cell Physiol | ||
|abstract=Skeletal muscle mitochondrial dysfunction has been linked to several disease states as well as the process of aging. A possible factor involved is the peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α (PGC-1α), a major player in the regulation of skeletal muscle mitochondrial metabolism. However, it is currently unknown whether PGC-1α, besides stimulating mitochondrial proliferation, also affects the functional capacity per mitochondrion. Therefore, we here tested whether PGC-1α overexpression, besides increasing mitochondrial content, also leads to intrinsic mitochondrial adaptations. Skeletal muscle mitochondria from 10 male, muscle-specific PGC-1α overexpressing mice (PGC-1αTg) and 8 wild-type (WT) mice were isolated. Equal mitochondrial quantities were then analyzed for their oxidative capacity by high-resolution respirometry, fuelled by a carbohydrate-derived (pyruvate) and a lipid (palmitoyl-CoA plus carnitine) substrate. Additionally, mitochondria were tested for reactive oxygen species (superoxide) production and fatty acid (FA)-induced uncoupling. PGC-1αTg mitochondria were characterized by an improved intrinsic mitochondrial fat oxidative capacity as evidenced by pronounced increase in ADP-stimulated respiration ( | |abstract=Skeletal muscle mitochondrial dysfunction has been linked to several disease states as well as the process of aging. A possible factor involved is the peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α [[PGC-1alpha|(PGC-1α)]], a major player in the regulation of skeletal muscle mitochondrial metabolism. However, it is currently unknown whether [[PGC-1α]], besides stimulating mitochondrial proliferation, also affects the functional capacity per mitochondrion. Therefore, we here tested whether [[PGC-1α]] overexpression, besides increasing mitochondrial content, also leads to intrinsic mitochondrial adaptations. Skeletal muscle mitochondria from 10 male, muscle-specific [[PGC-1α]] overexpressing mice (PGC-1αTg) and 8 wild-type (WT) mice were isolated. Equal mitochondrial quantities were then analyzed for their oxidative capacity by high-resolution respirometry, fuelled by a carbohydrate-derived (pyruvate) and a lipid (palmitoyl-CoA plus carnitine) substrate. Additionally, mitochondria were tested for reactive oxygen species (superoxide) production and fatty acid (FA)-induced uncoupling. PGC-1αTg mitochondria were characterized by an improved intrinsic mitochondrial fat oxidative capacity as evidenced by pronounced increase in ADP-stimulated respiration (''p'' < 0.001) and maximal uncoupled respiration (''p'' < 0.001) upon palmitoyl-CoA plus carnitine. Interestingly, intrinsic mitochondrial capacity on a carbohydrate-derived substrate tended to be reduced. Furthermore, the sensitivity to FA-induced uncoupling was diminished in PGC-1αTg mitochondria (''p'' = 0.02) and this was accompanied by a blunted reduction in mitochondrial ROS production upon fatty acids in PGC-1αTg vs. WT mitochondria (''p'' = 0.04). Uncoupling protein 3 (UCP3) levels were markedly reduced in PGC-1αTg mitochondria (''p'' < 0.001). Taken together, in addition to stimulating mitochondrial proliferation in skeletal muscle, we show here that overexpression of [[PGC-1α]] leads to intrinsic mitochondrial adaptations that seem restricted to fat metabolism. | ||
|keywords= | |keywords=Skeletal muscle, Mitochondria, Fat metabolism, ROS, Mitochondrial uncoupling | ||
|mipnetlab= | |mipnetlab=NL Maastricht Schrauwen P | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |||
|injuries=Oxidative stress;RONS | |||
|organism=Mouse | |||
|tissues=Skeletal muscle | |||
|preparations=Isolated mitochondria | |||
|couplingstates=LEAK, OXPHOS, ET | |||
|pathways=F, N | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 14:38, 13 November 2017
| Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) Enhanced lipid -but not carbohydrate- supported mitochondrial respiration in skeletal muscle of PGC-1α overexpressing mice. J Cell Physiol 227:1026-33. |
Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) J Cell Physiol
Abstract: Skeletal muscle mitochondrial dysfunction has been linked to several disease states as well as the process of aging. A possible factor involved is the peroxisome proliferator-activated receptor (PPAR) γ co-activator 1α (PGC-1α), a major player in the regulation of skeletal muscle mitochondrial metabolism. However, it is currently unknown whether PGC-1α, besides stimulating mitochondrial proliferation, also affects the functional capacity per mitochondrion. Therefore, we here tested whether PGC-1α overexpression, besides increasing mitochondrial content, also leads to intrinsic mitochondrial adaptations. Skeletal muscle mitochondria from 10 male, muscle-specific PGC-1α overexpressing mice (PGC-1αTg) and 8 wild-type (WT) mice were isolated. Equal mitochondrial quantities were then analyzed for their oxidative capacity by high-resolution respirometry, fuelled by a carbohydrate-derived (pyruvate) and a lipid (palmitoyl-CoA plus carnitine) substrate. Additionally, mitochondria were tested for reactive oxygen species (superoxide) production and fatty acid (FA)-induced uncoupling. PGC-1αTg mitochondria were characterized by an improved intrinsic mitochondrial fat oxidative capacity as evidenced by pronounced increase in ADP-stimulated respiration (p < 0.001) and maximal uncoupled respiration (p < 0.001) upon palmitoyl-CoA plus carnitine. Interestingly, intrinsic mitochondrial capacity on a carbohydrate-derived substrate tended to be reduced. Furthermore, the sensitivity to FA-induced uncoupling was diminished in PGC-1αTg mitochondria (p = 0.02) and this was accompanied by a blunted reduction in mitochondrial ROS production upon fatty acids in PGC-1αTg vs. WT mitochondria (p = 0.04). Uncoupling protein 3 (UCP3) levels were markedly reduced in PGC-1αTg mitochondria (p < 0.001). Taken together, in addition to stimulating mitochondrial proliferation in skeletal muscle, we show here that overexpression of PGC-1α leads to intrinsic mitochondrial adaptations that seem restricted to fat metabolism. • Keywords: Skeletal muscle, Mitochondria, Fat metabolism, ROS, Mitochondrial uncoupling
• O2k-Network Lab: NL Maastricht Schrauwen P
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: F, N
HRR: Oxygraph-2k
