Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

Koves, Timothy R.; Noland, Robert C.; Bates, Andrew L.; Henes, Sarah T.; Muoio, Deborah M.; Cortright, Ronald N.

doi:10.1152/ajpcell.00391.2004

Cited by 141 publications

(130 citation statements)

References 50 publications

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“…However, selectively greater increases in palmitate oxidation in SS mitochondria (ϩ100%) compared with IMF mitochondria (ϩ46%) have been observed previously in muscles of endurance trained rats (66), in which PGC-1␣ was undoubtedly also increased. All other reports (12)(13)(14), except one (15), have found that the mRNA abundance of skeletal muscle CPTI, whose protein product is a key regulator of fatty acid oxidation, was not altered by PGC-1␣ overexpression.…”

Section: Pgc-1␣-induced Fatty Acid Oxidation-mentioning

confidence: 45%

“…In one study from our laboratory (69) and in several others by Muoio and co-workers (2,66,70), the rates of fatty acid oxidation have been shown to be greater in mitochondria obtained from red muscle than in mitochondria obtained from white muscle. These studies suggest that there are intrinsic differences in the capacities to oxidize fatty acids by red and white muscle mitochondria.…”

Section: Pgc-1␣-induced Fatty Acid Oxidation-mentioning

confidence: 90%

“…Because previous reports have shown that SS mitochondria exhibit greater metabolic plasticity than IMF mitochondria (16,17,66), we examined proteins in SS and IMF mitochondria. In agreement with previous studies showing that PGC-1␣ induced the expression of COXIV and mTFA in C 2 C 12 skeletal muscle cells (44,65), PGC-1␣ also induced the expression of COXIV and mTFA proteins in skeletal muscle SS and IMF mitochondria.…”

Section: Pgc-1␣ Overexpression and Mitochondrial Proteins And Palmitatementioning

confidence: 99%

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Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Benton

Nickerson

Lally

et al. 2008

Journal of Biological Chemistry

196

232

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PGC-1␣ overexpression in skeletal muscle, in vivo, has yielded disappointing and unexpected effects, including disrupted cellular integrity and insulin resistance. These unanticipated results may stem from an excessive PGC-1␣ overexpression in transgenic animals. Therefore, we examined the effects of a modest PGC-1␣ overexpression in a single rat muscle, in vivo, on fuel-handling proteins and insulin sensitivity. We also examined whether modest PGC-1␣ overexpression selectively targeted subsarcolemmal (SS) mitochondrial proteins and fatty acid oxidation, because SS mitochondria are metabolically more plastic than intermyofibrillar (IMF) mitochondria. Among metabolically heterogeneous rat hindlimb muscles, PGC-1␣ was highly correlated with their oxidative fiber content and with substrate transport proteins (GLUT4, FABPpm, and FAT/ CD36) and mitochondrial proteins (COXIV and mTFA) but not with insulin-signaling proteins (phosphatidylinositol 3-kinase, IRS-1, and Akt2), nor with 5-AMP-activated protein kinase, ␣2 subunit, and HSL. Transfection of PGC-1␣ into the red (RTA) and white tibialis anterior (WTA) compartments of the tibialis anterior muscle increased PGC-1␣ protein by 23-25%. This also induced the up-regulation of transport proteins (FAT/CD36, 35-195%; GLUT4, 20 -32%) and 5-AMP-activated protein kinase, ␣2 subunit (37-48%), but not other proteins (FABPpm, IRS-1, phosphatidylinositol 3-kinase, Akt2, and HSL). SS and IMF mitochondrial proteins were also up-regulated, including COXIV (15-75%), FAT/CD36 (17-30%), and mTFA (15-85%). PGC-1␣ overexpression also increased palmitate oxidation in SS (RTA, ؉116%; WTA, ؉40%) but not in IMF mitochondria, and increased insulin-stimulated phosphorylation of AKT2 (28 -43%) and rates of glucose transport (RTA, ؉20%; WTA, ؉38%). Thus, in skeletal muscle in vivo, a modest PGC-1␣ overexpression up-regulated selected plasmalemmal and mitochondrial fuel-handling proteins, increased SS (not IMF) mitochondrial fatty acid oxidation, and improved insulin sensitivity.

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Section: Pgc-1␣-induced Fatty Acid Oxidation-mentioning

confidence: 45%

Section: Pgc-1␣-induced Fatty Acid Oxidation-mentioning

confidence: 90%

Section: Pgc-1␣ Overexpression and Mitochondrial Proteins And Palmitatementioning

confidence: 99%

See 1 more Smart Citation

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Benton

Nickerson

Lally

et al. 2008

Journal of Biological Chemistry

196

232

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“…Activation of PPAR␦ (38) and overexpression of PGC-1␣ (36) upregulate fatty acid oxidation. Endurance-type training has also been shown to increase fatty acid oxidation in the vastus lateralis muscle of obese women (13) and in red and white gastrocnemius muscle of rats run on a treadmill for 10 wk (30). Additional studies demonstrate that the capacity to oxidize palmitate in skeletal muscle is significantly reduced with human obesity and negatively associated with body mass index (28).…”

Section: Discussionmentioning

confidence: 98%

Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

Morris¹,

Laye²,

Lees³

et al. 2008

Journal of Applied Physiology

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Morris RT, Laye MJ, Lees SJ, Rector RS, Thyfault JP, Booth FW. Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat. J Appl Physiol 104: 708-715, 2008. First published December 13, 2007 doi:10.1152/japplphysiol.01034.2007.-The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 ϫ Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-␣ type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-␦ and peroxisome proliferator-activated receptor-␥ coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle. physical activity; oxidative stress; chronic disease THE INCIDENCE OF OVERWEIGHT in children and adolescents has tripled to 17.1% in 2004 from the late 1960s in the United States (40). Obesity is caused by a positive energy balance, with excess energy intake and insufficient physical activity being major causal factors. An understanding of the biological basis for energy partitioning from fat to skeletal muscle is imperative for prevention of fat gain as young subjects grow to adults.The Otsuka Long-Evans Tokushima fatty (OLETF) rat, which was selectively bred for null expression of the cholecystokinin (CCK)-1 receptor (27), is an animal model characterized by hyperphagia, obesity, decreased glucose infusion rate in a euglycemic clamp at 16 wk of age, and hyperinsulinemia at 24 wk of age in respons...

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“…Mitochondria are located either around the nuclei, this subgroup is called subsarcolemmal mitochondria, or nestled between myofibrils. These mitochondria are named intermyofibrillar and have distinct activity from subsarcolemmal ones (Koves et al, 2005;Mollica et al, 2006). Intermyofibrillar mitochondria are mainly dedicated to energy production for muscle fiber contraction.…”

Section: Basic Knowledge On Mitochondrial Functioningmentioning

confidence: 99%

Evaluation of Mitochondrial Functions and Dysfunctions in Muscle Biopsy Samples

Capel¹,

Barquissau²,

Richard³

et al. 2012

Muscle Biopsy

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Subsarcolemmal and intermyofibrillar mitochondria play distinct roles in regulating skeletal muscle fatty acid metabolism

Cited by 141 publications

References 50 publications

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Modest PGC-1α Overexpression in Muscle in Vivo Is Sufficient to Increase Insulin Sensitivity and Palmitate Oxidation in Subsarcolemmal, Not Intermyofibrillar, Mitochondria

Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

Evaluation of Mitochondrial Functions and Dysfunctions in Muscle Biopsy Samples

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