Impaired expression of NADH dehydrogenase subunit 1 and PPARγ coactivator-1 in skeletal muscle of ZDF rats

Jové, Mireia; Salla, Joel; Planavila, Anna; Cabrero, Ágatha; Michalik, Liliane; Wahli, Walter; Laguna, Juan C.; Vázquez‐Carrera, Manuel

doi:10.1194/jlr.m300208-jlr200

Cited by 58 publications

(38 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other studies in insulin-resistant rodents have reported reduced expression of PGC-1␣ and other markers of mitochondrial metabolism in muscle (21)(22)(23)(24). The reason for the disparity in results is unclear but may be related to methodological factors such as diet composition, the length of high-fat feeding, or the particular muscle groups examined (i.e., quadriceps versus gastrocnemius bundle).…”

Section: Discussionmentioning

confidence: 57%

See 1 more Smart Citation

Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle

et al. 2007

View full text Add to dashboard Cite

A reduced capacity for mitochondrial fatty acid oxidation in skeletal muscle has been proposed as a major factor leading to the accumulation of intramuscular lipids and their subsequent deleterious effects on insulin action. Here, we examine markers of mitochondrial fatty acid oxidative capacity in rodent models of insulin resistance associated with an oversupply of lipids. C57BL/6J mice were fed a high-fat diet for either 5 or 20 weeks. Several markers of muscle mitochondrial fatty acid oxidative capacity were measured, including 14 C-palmitate oxidation, palmitoyl-CoA oxidation in isolated mitochondria, oxidative enzyme activity (citrate synthase, ␤-hydroxyacyl CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, and carnitine palmitoyl-transferase 1), and expression of proteins involved in mitochondrial metabolism. Enzyme activity and mitochondrial protein expression were also examined in muscle from other rodent models of insulin resistance. Compared with standard diet-fed controls, muscle from fat-fed mice displayed elevated palmitate oxidation rate (5 weeks ؉23%, P < 0.05, and 20 weeks ؉29%, P < 0.05) and increased palmitoyl-CoA oxidation in isolated mitochondria (20 weeks ؉49%, P < 0.01). Furthermore, oxidative enzyme activity and protein expression of peroxisome proliferator-activated receptor ␥ coactivator (PGC)-1␣, uncoupling protein (UCP) 3, and mitochondrial respiratory chain subunits were significantly elevated in fat-fed animals. A similar pattern was present in muscle of fat-fed rats, obese Zucker rats, and db/db mice, with increases observed for oxidative enzyme activity and expression of PGC-1␣, UCP3, and subunits of the mitochondrial respiratory chain. These findings suggest that high lipid availability does not lead to intramuscular lipid accumulation and insulin resistance in rodents by decreasing muscle mitochondrial fatty acid oxidative capacity.

show abstract

Section: Discussionmentioning

confidence: 57%

“…Studies (3,16 -20) have shown mitochondrial fatty acid oxidation and the activity of oxidative enzymes are elevated in muscle of fat-fed rats and obese Zucker rats. Equally, however, several recent studies (21)(22)(23)(24) in rodent models of insulin resistance have reported deficits in a variety of markers of mitochondrial metabolism in muscle.…”

mentioning

confidence: 99%

Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Diabetes is a strong risk factor for PAD, and PGC-1␣ is repressed in diabetic skeletal muscle in both rodents and humans (45)(46)(47), suggesting that PGC-1␣ insufficiency may predispose to, or worsen PAD. The data presented here, combined with our previous studies (26), suggest that the benefits of exercise in PAD may also in part be mediated by PGC-1␣.…”

Section: Discussionmentioning

confidence: 99%

The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscle

Chinsomboon

Ruas

Gupta

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

347

369

View full text Add to dashboard Cite

Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPAR␥ coactivator (PGC)-1␣ is a potent transcriptional coactivator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1␣ mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1␣ in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1␣ from an alternate promoter. The induction of PGC-1␣ depended on ␤-adrenergic signaling. ␤-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1␣. The orphan nuclear receptor ERR␣ mediated the induction of VEGF by PGC-1␣, and mice lacking ERR␣ also failed to increase vascular density after exercise. These data demonstrate that ␤-adrenergic stimulation of a PGC-1␣/ERR␣/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle.VEGF ͉ ERR␣ ͉ ␤-adrenergic

show abstract

“…We (10) and other researchers (11)(12)(13) have reported that insulin-resistant states are characterized by a reduction in skeletal muscle of peroxisome proliferator-activated receptor (PPAR)␥ coactivator-1 (PGC-1), the transcriptional coactivator driving the expression of many genes coding for proteins in mitochondria. PGC-1 was initially identified as a protein that interacted with PPAR␥ (14).…”

mentioning

confidence: 99%

Palmitate-Mediated Downregulation of Peroxisome Proliferator–Activated Receptor-γ Coactivator 1α in Skeletal Muscle Cells Involves MEK1/2 and Nuclear Factor-κB Activation

et al. 2006

View full text Add to dashboard Cite

The mechanisms by which elevated levels of free fatty acids cause insulin resistance are not well understood. Previous studies have reported that insulin-resistant states are characterized by a reduction in the expression of peroxisome proliferator-activated receptor-␥ coactivator (PGC)-1, a transcriptional activator that promotes oxidative capacity in skeletal muscle cells. However, little is known about the factors responsible for reduced PGC-1 expression. The expression of PGC-1 mRNA levels was assessed in C2C12 skeletal muscle cells exposed to palmitate either in the presence or in the absence of several inhibitors to study the biochemical pathways involved. We report that exposure of C2C12 skeletal muscle cells to 0.75 mmol/l palmitate, but not oleate, reduced PGC-1␣ mRNA levels (66%; P < 0.001), whereas PGC-1␤ expression was not affected. Palmitate led to mitogen-activated protein kinase (MAPK)-extracellular signal-related kinase (ERK) 1/2 (MEK1/2) activation. In addition, pharmacological inhibition of this pathway by coincubation of the palmitate-exposed cells with the MEK1/2 inhibitors PD98059 and U0126 prevented the downregulation of PGC-1␣. Furthermore, nuclear factor-B (NF-B) activation was also involved in palmitatemediated PGC-1␣ downregulation, since the NF-B inhibitor parthenolide prevented a decrease in PGC-1␣ expression. These findings indicate that palmitate reduces PGC-1␣ expression in skeletal muscle cells through a mechanism involving MAPK-ERK and NF-B activation.

show abstract

Impaired expression of NADH dehydrogenase subunit 1 and PPARγ coactivator-1 in skeletal muscle of ZDF rats

Cited by 58 publications

References 44 publications

Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle

Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle

The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscle

Palmitate-Mediated Downregulation of Peroxisome Proliferator–Activated Receptor-γ Coactivator 1α in Skeletal Muscle Cells Involves MEK1/2 and Nuclear Factor-κB Activation

Contact Info

Product

Resources

About