Diet-induced obesity and acute hyperlipidemia reduce IκBα levels in rat skeletal muscle in a fiber-type dependent manner

2006 ◽  
Vol 290 (1) ◽  
pp. R233-R240 ◽  
Author(s):  
Bankim A. Bhatt ◽  
John J. Dube ◽  
Nikolas Dedousis ◽  
Jodie A. Reider ◽  
Robert M. O’Doherty
Keyword(s):  
Skeletal Muscle ◽  
P38 Mapk ◽  
Fiber Type ◽  
Dependent Manner ◽  
Rat Skeletal Muscle ◽  
Diet Induced Obesity ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Fat Feeding ◽  
Increased Activity

Increased activity of proinflammatory/stress pathways has been implicated in the pathogenesis of insulin resistance in obesity. However, the effects of obesity on the activity of these pathways in skeletal muscle, the major insulin-sensitive tissue by mass, are poorly understood. Furthermore, the mechanisms that activate proinflammatory/stress pathways in obesity are unknown. The present study addressed the effects of diet-induced obesity (DIO; 6 wk of high-fat feeding) and acute (6-h) hyperlipidemia (HL) in rats on activity of IKK/IκB/NF-κB c-Jun NH2-terminal kinase, and p38 MAPK in three skeletal muscles differing in fiber type [superficial vastus (Vas; fast twitch-glycolytic), soleus (Sol; slow twitch-oxidative), and gastrocnemius (Gas; mixed)]. DIO decreased the levels of the IκBα in Vas (24 ± 3%, P = 0.001, n = 8) but not in Sol or Gas compared with standard chow-fed controls. Similar to DIO, HL decreased IκBα levels in Vas (26 ± 5%, P = 0.006, n = 6) and in Gas (15 ± 4%, P = 0.01, n = 7) but not in Sol compared with saline-infused controls. Importantly, the fiber-type-dependent effects on IκBα levels could not be explained by differential accumulation of triglyceride in Sol and Vas. HL, but not DIO, decreased phospho-p38 MAPK levels in Vas (41 ± 7% P = 0.004, n = 6) but not in Sol or Gas. Finally, skeletal muscle c-Jun NH2-terminal kinase activity was unchanged by DIO or HL. We conclude that diet-induced obesity and acute HL reduce IκBα levels in rat skeletal muscle in a fiber-type-dependent manner.

Characterization of RyR1-slow, a ryanodine receptor specific to slow-twitch skeletal muscle

2000 ◽  
Vol 279 (5) ◽  
pp. R1889-R1898 ◽  
Author(s):  
Jeffery Morrissette ◽  
Le Xu ◽  
Alexandra Nelson ◽  
Gerhard Meissner ◽  
Barbara A. Block
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Fiber Type ◽  
Ryanodine Receptors ◽  
Open Probability ◽  
Dependent Inhibition ◽  
Single Channel Activity ◽  
Intracellular Ca ◽  
Slow Twitch ◽  
Fast Twitch

Two distinct skeletal muscle ryanodine receptors (RyR1s) are expressed in a fiber type–specific manner in fish skeletal muscle (11). In this study, we compare [3H]ryanodine binding and single channel activity of RyR1-slow from fish slow-twitch skeletal muscle with RyR1-fast and RyR3 isolated from fast-twitch skeletal muscle. Scatchard plots indicate that RyR1-slow has a lower affinity for [3H]ryanodine when compared with RyR1-fast. In single channel recordings, RyR1-slow and RyR1-fast had similar slope conductances. However, the maximum open probability (Po) of RyR1-slow was threefold less than the maximum Po of RyR1-fast. Single channel studies also revealed the presence of two populations of RyRs in tuna fast-twitch muscle (RyR1-fast and RyR3). RyR3 had the highest Po of all the RyR channels and displayed less inhibition at millimolar Ca2+. The addition of 5 mM Mg-ATP or 2.5 mM β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP) to the channels increased the Po and [3H]ryanodine binding of both RyR1s but also caused a shift in the Ca2+ dependency curve of RyR1-slow such that Ca2+-dependent inactivation was attenuated. [3H]ryanodine binding data also showed that Mg2+-dependent inhibition of RyR1-slow was reduced in the presence of AMP-PCP. These results indicate differences in the physiological properties of RyRs in fish slow- and fast-twitch skeletal muscle, which may contribute to differences in the way intracellular Ca2+ is regulated in these muscle types.

scholarly journals Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers

2001 ◽  
Vol 155 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Yewei Liu ◽  
Zoltán Cseresnyés ◽  
William R. Randall ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Nuclear Translocation ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers ◽  
Slow Twitch ◽  
Nuclear Foci ◽  
Fast Twitch

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.

Diazepam reveals different rate-limiting processes in rat skeletal muscle contraction

1987 ◽  
Vol 65 (2) ◽  
pp. 272-273 ◽  
Author(s):  
Michael Chua ◽  
Angela F. Dulhunty
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Calcium Binding ◽  
Extensor Digitorum Longus ◽  
Calcium Uptake ◽  
Rat Skeletal Muscle ◽  
Skeletal Muscle Contraction ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Rate Limiting

The action of the tranquilizer diazepam on rat skeletal muscle showed that relaxation of isometric twitches is controlled by different processes in extensor digitorum longus (fast-twitch) and soleus (slow-twitch) muscles. Diazepam caused an increase in the amplitude of twitches in fibres from both muscles but increased the twitch duration only in soleus. The amplitude of fused tetani were reduced in both muscles and the rate of relaxation after the tetanus slowed by as much as 34% when the amplitude of the tetanus was reduced by only 11%. The slower tetanic relaxation indicated that calcium uptake by the sarcoplasmic reticulum was slower than normal in slow- and fast-twitch fibres. We conclude therefore that calcium uptake by the sarcoplasmic reticulum is rate limiting for twitch relaxation in slow-twitch but not fast-twitch fibres and suggest that calcium binding to parvalbumin controls relaxation in the fast fibres.

scholarly journals IL-6 and epinephrine have divergent fiber type effects on intramuscular lipolysis

2013 ◽  
Vol 115 (10) ◽  
pp. 1457-1463 ◽  
Author(s):  
Tara L. MacDonald ◽  
Zhongxiao Wan ◽  
Scott Frendo-Cumbo ◽  
David J. Dyck ◽  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Ex Vivo ◽  
Fiber Type ◽  
Dependent Manner ◽  
Glycerol Release ◽  
Slow Twitch Muscle ◽  
Murine Skeletal Muscle ◽  
Amp Activated Protein Kinase ◽  
Fast Twitch

IL-6 is an exercise-regulated myokine that has been suggested to increase lipolysis in fast-twitch skeletal muscle. However, it is not known if a similar effect is present in slow-twitch muscle. Furthermore, epinephrine increases IL-6 secretion from skeletal muscle, suggesting that IL-6 could play a role in mediating the lipolytic effects of catecholamines. The purpose of this study was to determine whether IL-6 stimulates skeletal muscle lipolysis in a fiber type dependent manner and is required for epinephrine-stimulated lipolysis in murine skeletal muscle. Soleus and extensor digitorum longus (EDL) muscles from male C57BL/6J wild-type and IL-6−/− mice were incubated with 1 μM (183 ng/ml) epinephrine or 75 ng/ml recombinant IL-6 (rIL-6) for 60 min. IL-6 treatment increased 5′-AMP-activated protein kinase and signal transducer and activator of transcription 3 phosphorylation and glycerol release in isolated EDL but not soleus muscles from C57BL/6J mice. Conversely, epinephrine increased glycerol release in soleus but not EDL muscles from C57BL/6J mice. Basal lipolysis was elevated in soleus muscle from IL-6−/− mice, and this was associated with increases in adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58). The increase in ATGL content does not appear to be due to a loss of IL-6's direct effects, because ex vivo treatment with IL-6 failed to alter the expression of ATGL mRNA in soleus muscle. In summary, IL-6 stimulates lipolysis in glycolytic but not oxidative muscle, whereas the opposite fiber type effect is seen with epinephrine. The absence of IL-6 indirectly upregulates lipolysis, and this is associated with increases in ATGL and its coactivator CGI-58.

Duality of G protein-coupled mechanisms for β-adrenergic activation of NKCC activity in skeletal muscle

2002 ◽  
Vol 283 (4) ◽  
pp. C1025-C1032 ◽  
Author(s):  
Aidar R. Gosmanov ◽  
Jennifer A. Wong ◽  
Donald B. Thomason
Keyword(s):  
Skeletal Muscle ◽  
G Protein ◽  
Mapk Pathway ◽  
Dependent Manner ◽  
Mapk Phosphorylation ◽  
Akt Activation ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Erk Activity ◽  
G Protein Coupled

Skeletal muscle Na+-K+-2Cl− cotransporter (NKCC) activity provides a potential mechanism for regulated K+uptake. β-Adrenergic receptor (β-AR) activation stimulates skeletal muscle NKCC activity in a MAPK pathway-dependent manner. We examined potential G protein-coupled pathways for β-AR-stimulated NKCC activity. Inhibition of Gs-coupled PKA blocked isoproterenol-stimulated NKCC activity in both the slow-twitch soleus muscle and the fast-twitch plantaris muscle. However, the PKA-activating agents cholera toxin, forskolin, and 8-bromo-cAMP (8-BrcAMP) were not sufficient to activate NKCC in the plantaris and partially stimulated NKCC activity in the soleus. Isoproterenol-stimulated NKCC activity in the soleus was abolished by pretreatment with pertussis toxin (PTX), indicating a Gi-coupled mechanism. PTX did not affect the 8-BrcAMP-stimulated NKCC activity. PTX treatment also precluded the isoproterenol-mediated ERK1/2 MAPK phosphorylation in the soleus, consistent with NKCC's MAPK dependency. Inhibition of isoproterenol-stimulated ERK activity by PTX treatment was associated with an increase in Akt activation and phosphorylation of Raf-1 on the inhibitory residue Ser259. These results demonstrate a novel, muscle phenotype-dependent mechanism for β-AR-mediated NKCC activation that involves both Gs and Giprotein-coupled mechanisms.

Enhanced technique to measure proteins in single segments of human skeletal muscle fibers: fiber-type dependence of AMPK-α1 and -β1

2011 ◽  
Vol 110 (3) ◽  
pp. 820-825 ◽  
Author(s):  
Robyn M. Murphy
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Significant Advance ◽  
Vastus Lateralis Muscle ◽  
Fiber Types ◽  
Freeze Dried ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Muscle Biopsies

Human physiological studies typically use skeletal muscle biopsies from the heterogeneous vastus lateralis muscle comprised of both fast-twitch and slow-twitch fiber types. It is likely that potential changes of physiological importance are overlooked because fiber-type specific responses may not be apparent in the whole muscle preparation. A technological advance in Western blotting is presented where proteins are analyzed in just one small segment (<2 mm) of individual fibers dissected from freeze-dried muscle samples using standard laboratory equipment. A significant advance is being able to classify every fiber at the level of both contractile (myosin heavy chain and tropomyosin) and sarcoplasmic reticulum [sarco(endo)plasmic reticulum Ca2+-ATPase type 1] properties and then being able to measure specific proteins in the very same segments. This removes the need to fiber type segments before further analyses and, as such, dramatically reduces the time required for sample collection. Compared with slow-twitch fibers, there was less AMP-activated protein kinase (AMPK)-α1 (∼25%) and AMPK-β1 (∼60%) in fast-twitch fibers from human skeletal muscle biopsies.

scholarly journals Localization of sarcoplasmic reticulum proteins in rat skeletal muscle by immunofluorescence.

1979 ◽  
Vol 80 (2) ◽  
pp. 372-384 ◽  
Author(s):  
A O Jorgensen ◽  
V Kalnins ◽  
D H MacLennan
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Immunofluorescent Staining ◽  
Mammalian Skeletal Muscle ◽  
Rat Skeletal Muscle ◽  
Ultrastructural Studies ◽  
Band Region ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Cryostat Sections

Ca++-Mg++-dependent ATPase and calsequestrin, the major intrinsic and extrinsic proteins, respectively, of the sarcoplasmic reticulum, were localized in cryostat sections of adult rat skeletal muscle by immunofluorescent staining and phase-contrast microscopy. Relatively high concentrations of both the ATPase and calsequestrin were found in fast-twitch myofibers while a very low concentration of the ATPase and a moderate concentration of calsequestrin were found in slow-twitch myofibers. These findings are consistent with previous biochemical studies of the isolated sarcoplasmic reticulum of slow-twitch and fast-twitch mammalian muscles. The distribution of the ATPase in muscle fibers is distinctly different from that of calsequestrin. While calsequestrin is present only near the interface between the I- and A-band regions of the sarcomere, the ATPase is found throughout the I-band region as well as in the center of the A-band region. In comparing these results with in situ ultrastructural studies of the distribution of sarcoplasmic reticulum in fast-twitch muscle, it appears that the ATPase is rather uniformly distributed throughout the sarcoplasmic reticulum while calsequestrin is almost exclusively confined to those regions of the membrane system which correspond to terminal cisternae. Fluorescent staining with these antisera was not observed in vascular smooth muscle cells present in the cryostat sections of the mammalian skeletal muscle used in this study.

Effect of colchicine on alkaline triglyceride lipase activity and triglyceride content in rat skeletal muscle

1988 ◽  
Vol 66 (12) ◽  
pp. 1555-1559 ◽  
Author(s):  
J. Gorski ◽  
W. C. Miller ◽  
W. K. Palmer ◽  
L. B. Oscai
Keyword(s):  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Lipase Activity ◽  
Colchicine Treatment ◽  
Rat Skeletal Muscle ◽  
Potent Inducer ◽  
Triglyceride Content ◽  
Slow Twitch ◽  
Muscle Groups ◽  
Fast Twitch

One purpose of this study was to determine if colchicine increased intracellular alkaline triglyceride (TG) lipase activity above control levels in rat skeletal muscle. The second aim was to determine the effects of colchicine treatment on the concentration of TG in skeletal muscle. The results show that colchicine was a potent inducer of alkaline TG lipase activity, increasing enzyme activity approximately twofold in slow-twitch red, fast-twitch red, and fast-twitch white muscle types. It was found that in slow-twitch red soleus and fast-twitch red vastus, the two muscle groups with the highest levels of enzyme activity, 76% or more of enzyme activity resides in the intracellular compartment. These results provide evidence that colchicine blocks the export of alkaline TG lipase from skeletal muscle cells similar to that seen in the heart. The finding that TG were reduced at a time when enzyme activity was elevated suggests that intracellular alkaline TG lipase may be playing a role in the hydrolysis of the intramuscular TG droplet.

Sign in / Sign up

Export Citation Format

Share Document