Reduced lipoprotein lipase activity in postural skeletal muscle during aging

2001 ◽  
Vol 91 (2) ◽  
pp. 687-692 ◽  
Author(s):  
Lionel Bey ◽  
Enas Areiqat ◽  
Andrea Sano ◽  
Marc T. Hamilton
Keyword(s):  
Skeletal Muscle ◽  
Lipoprotein Lipase ◽  
Soleus Muscle ◽  
Tibialis Anterior ◽  
Weight Bearing ◽  
Fischer 344 Rats ◽  
Protein Mass ◽  
Fischer 344 ◽  
Mrna Concentration ◽  
Postural Muscle

Lipoprotein lipase (LPL) is a key enzyme for fatty acid and lipoprotein metabolism in muscle. However, the effect of aging on LPL regulation in skeletal muscle is unknown. We report the effect of aging on LPL regulation in the soleus (red oxidative postural) muscle and the tibialis anterior (white glycolytic non-weight-bearing) muscle in 4- and 24-mo-old Fischer 344 rats and 18- and 31-mo-old Fischer 344 × Brown-Norway F1 (F-344 × BN F1) rats. Total and heparin-releasable LPL (HR-LPL) activities were decreased 38% ( P< 0.01) and 52% ( P < 0.05), respectively, in the soleus muscle of the older Fischer 344 rats. There was a 32% reduction ( P < 0.05) of total LPL protein mass in the soleus muscle with aging. The results were confirmed in another strain. A decrease of total LPL activity (−50%, P < 0.05) was also found in the soleus muscle between 18- and 31-mo-old F-344 × BN F1 rats. LPL mRNA concentration in the soleus muscle was not different between ages. Total LPL protein mass was reduced by 46% ( P < 0.05) in the soleus muscle of the 31-mo-old F-344 × BN F1 rats. In the tibialis anterior muscle, neither LPL activity nor mRNA concentration was affected by age in either strain. In conclusion, LPL regulation in a non-weight-bearing muscle was not affected by aging. However, there was a pronounced reduction in LPL activity and LPL protein mass in postural muscle with aging.

Nerve-responsive troponin I slow promoter does not respond to unloading

1998 ◽  
Vol 84 (3) ◽  
pp. 1083-1087 ◽  
Author(s):  
David S. Criswell ◽  
Vanessa R. M. Hodgson ◽  
Edna C. Hardeman ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Body Mass ◽  
Soleus Muscle ◽  
Troponin I ◽  
Weight Bearing ◽  
Mouse Line ◽  
Base Pairs ◽  
Transgenic Mouse Line ◽  
Protein Isoform ◽  
Muscle Unloading

We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the −4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice (∼30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls ( n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (−6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (−25%) and soleus mass relative to body mass (−16%) were both lower ( P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease ( P < 0.05) in the abundance of endogenous TnIs mRNA (μg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference ( P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

1999 ◽  
Vol 277 (2) ◽  
pp. R601-R606 ◽  
Author(s):  
Christian J. Carlson ◽  
Frank W. Booth ◽  
Scott E. Gordon
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Soleus Muscle ◽  
Fiber Type ◽  
Weight Bearing ◽  
Mrna Abundance ◽  
Hindlimb Unloading ◽  
Negative Regulator ◽  
Type I ◽  
Mrna Levels

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S.-J. Lee. Nature 387: 83–90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation ( r = 0.725, P < 0.0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

scholarly journals Secondary hyperparathyroidism downregulates lipoprotein lipase expression in chronic renal failure

1997 ◽  
Vol 273 (6) ◽  
pp. F925-F930 ◽  
Author(s):  
N. D. Vaziri ◽  
X. Q. Wang ◽  
K. Liang
Keyword(s):  
Skeletal Muscle ◽  
Renal Failure ◽  
Catalytic Activity ◽  
Chronic Renal Failure ◽  
Secondary Hyperparathyroidism ◽  
Lipoprotein Lipase ◽  
Male Rats ◽  
Northern Analysis ◽  
Protein Mass ◽  
Lipase Expression

In a recent study, we found marked downregulation of lipoprotein lipase (LPL) gene expression in fat, myocardium, and skeletal muscle of rats with chronic renal failure (CRF). Recently, hepatic lipase expression was shown to be depressed in CRF rats, and parathyroidectomy (PTX) was shown to reverse this abnormality. This study was undertaken to determine whether downregulation of LPL expression in CRF is due to secondary hyperparathyroidism. Accordingly, LPL mRNA (Northern analysis), protein mass (Western analysis using mouse anti-bovine LPL monoclonal antibody, 5D2), and catalytic activity of the fat pad and soleus muscle were compared in five-sixths-nephrectomized male rats (CRF), parathyroidectomized CRF rats, and sham-operated control animals. The CRF animals exhibited marked hypertriglyceridemia and significant reductions of fat and skeletal muscle LPL mRNA abundance, protein mass, and catalytic activity ( P < 0.05 vs. controls, for all parameters). PTX completely normalized the LPL mRNA, protein mass, and enzymatic activity and partially ameliorated the CRF hypertriglyceridemia ( P < 0.05 vs. CRF group, for all parameters). Thus secondary hyperparathyroidism is responsible for impaired LPL expression in experimental CRF. This abnormality is completely corrected by PTX.

Ontogenetic, gravity-dependent development of rat soleus muscle

2001 ◽  
Vol 280 (4) ◽  
pp. C1008-C1016 ◽  
Author(s):  
Yoshinobu Ohira ◽  
Takato Tanaka ◽  
Tomoo Yoshinaga ◽  
Fuminori Kawano ◽  
Takeshi Nomura ◽  
...  
Keyword(s):  
Soleus Muscle ◽  
Weight Bearing ◽  
Postnatal Period ◽  
Hindlimb Unloading ◽  
Full Weight Bearing ◽  
Type I ◽  
Myosin Isoforms ◽  
Normal Transition ◽  
Postural Muscle ◽  
Rat Soleus Muscle

We tested the hypothesis that rat soleus muscle fiber growth and changes in myosin phenotype during the postnatal, preweaning period would be largely independent of weight bearing. The hindlimbs of one group of pups were unloaded intermittently from postnatal day 4 to day 21: the pups were isolated from the dam for 5 h during unloading and returned for nursing for 1 h. Control pups were either maintained with the dam as normal or put on an alternating feeding schedule as described above. The enlargement of mass (∼3 times), increase in myonuclear number (∼1.6 times) and myonuclear domain (∼2.6 times), and transformation toward a slow fiber phenotype (from 56 to 70% fibers expressing type I myosin heavy chain) observed in controls were inhibited by hindlimb unloading. These properties were normalized to control levels or higher within 1 mo of reambulation beginning immediately after the unloading period. Therefore, chronic unloading essentially stopped the ontogenetic developmental processes of 1) net increase in DNA available for transcription, 2) increase in amount of cytoplasm sustained by that DNA pool, and 3) normal transition of myosin isoforms that occur in some fibers from birth to weaning. It is concluded that normal ontogenetic development of a postural muscle is highly dependent on the gravitational environment even during the early postnatal period, when full weight-bearing activity is not routine.

scholarly journals Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloading

2007 ◽  
Vol 292 (3) ◽  
pp. C1192-C1203 ◽  
Author(s):  
Zhi Bin Yu ◽  
Fang Gao ◽  
Han Zhong Feng ◽  
Jian-Ping Jin
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Troponin I ◽  
Troponin T ◽  
Weight Bearing ◽  
Regulatory Protein ◽  
Differential Regulation ◽  
Hindlimb Unloading ◽  
Protein Isoforms ◽  
Hindlimb Suspension

Weight-bearing skeletal muscles change phenotype in response to unloading. Using the hindlimb suspension rat model, we investigated the regulation of myofilament protein isoforms in correlation to contractility. Four weeks of continuous hindlimb unloading produced progressive atrophy and contractility changes in soleus but not extensor digitorum longus muscle. The unloaded soleus muscle also had decreased fatigue resistance. Along with the decrease of myosin heavy chain isoform I and IIa and increase of IIb and IIx, coordinated regulation of thin filament regulatory protein isoforms were observed: γ- and β-tropomyosin decreased and α-tropomyosin increased, resulting in an α/β ratio similar to that in normal fast twitch skeletal muscle; troponin I and troponin T (TnT) both showed decrease in the slow isoform and increases in the fast isoform. The TnT isoform switching began after 7 days of unloading and TnI isoform showed detectable changes at 14 days while other protein isoform changes were not significant until 28 days of treatment. Correlating to the early changes in contractility, especially the resistance to fatigue, the early response of TnT isoform regulation may play a unique role in the adaptation of skeletal muscle to unloading. When the fast TnT gene expression was upregulated in the unloaded soleus muscle, alternative RNA splicing switched to produce more high molecular weight acidic isoforms, reflecting a potential compensation for the decrease of slow TnT that is critical to skeletal muscle function. The results demonstrate that differential regulation of TnT isoforms is a sensitive mechanism in muscle adaptation to functional demands.

Exercise induces human lipoprotein lipase gene expression in skeletal muscle but not adipose tissue

1995 ◽  
Vol 268 (2) ◽  
pp. E229-E236 ◽  
Author(s):  
R. L. Seip ◽  
T. J. Angelopoulos ◽  
C. F. Semenkovich
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Molecular Mechanisms ◽  
Plasma Lipids ◽  
Mrna Level ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Protein Mass ◽  
Supervised Exercise

Lipoprotein lipase (LPL) is regulated by exercise in humans, but the effects of exercise on LPL expression in different tissues and the molecular mechanisms involved are unclear. We assessed the effects of 5-13 consecutive days of supervised exercise on tissue LPL expression as well as fasting plasma lipids and lipoproteins in 32 sedentary, weight-stable adult men. In skeletal muscle, exercise training increased the mean LPL mRNA level by 117% (P = 0.037), LPL protein mass by 53% (P = 0.038), and total LPL enzyme activity by 35% (P = 0.025). In adipose tissue, mean LPL mRNA, protein mass, and activity did not change. Exercise decreased triglycerides [from 172 +/- 4.3 to 127 +/- 3.2 (SE) mg/dl, P = 0.002], total cholesterol (from 188 +/- 1.2 to 181 +/- 1.0 mg/dl, P = 0.011), and very low-density lipoprotein-cholesterol (from 30.1 +/- 0.9 to 22.0 +/- 0.8, P = 0.004) and increased high-density lipoprotein cholesterol (HDL-C; from 43.4 +/- 0.35 to 45.0 +/- 0.37, P = 0.030) and HDL2-C (from 6.6 +/- 0.21 to 7.7 +/- 0.19, P = 0.021). Changes in muscle but not adipose tissue heparin-releasable LPL activity were inversely correlated (r = -0.435, P < 0.034) with changes in triglycerides. These data suggest the existence of an exercise stimulus intrinsic to skeletal muscle, which raises LPL activity in part by pretranslational mechanisms, a process that contributes to the improvement in circulating lipids seen with physical activity.

Organ blood flow in Fischer-344 rats bearing MCA-induced sarcoma

1991 ◽  
Vol 71 (5) ◽  
pp. 1674-1678 ◽  
Author(s):  
P. A. Van Leeuwen ◽  
J. R. Bading ◽  
N. A. Vydelingum ◽  
R. N. Younes ◽  
P. de Rooij ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Organ Blood Flow ◽  
Fischer 344 Rats ◽  
Venous Flow ◽  
Fischer 344 ◽  
Abdominal Organs ◽  
Hindlimb Muscle ◽  
Distribution Of Cardiac Output ◽  
Host Tissues

Although blood flow is central to systemic metabolism, little is known about the effect of tumor on the perfusion of host tissues. This study evaluated the effects of a methylcholanthrene-induced sarcoma on blood flow to intra-abdominal organs and skeletal muscle of Fischer-344 rats anesthetized with pentobarbital sodium. Animals were studied by aortic injection of radiolabeled microspheres when the tumors reached 20% of body weight. Total-organ arterial flows in spleen, liver, small intestine, and pancreas were each increased to 50–150% in tumor bearers relative to controls (P less than 0.05). Portal venous flow and flow per gram to hindlimb muscle were 60 +/- 20 and 300 +/- 100% greater, respectively, in tumor-bearing animals (P less than 0.005). This study shows that tumor growth can be associated with large changes in organ flow and distribution of cardiac output. The increase in skeletal muscle flow in the tumor bearers, which lost normal tissue weight relative to pair-fed controls (P less than 0.05), is in marked contrast to decreased muscle flow previously observed in simple starvation.

scholarly journals Adrenergic stimulated skeletal muscle glycogenolysis in perfused hindlimbs of young and old male Fischer 344 rats

1994 ◽  
Vol 266 (3) ◽  
pp. R749-R755
Author(s):  
L. M. Larkin ◽  
B. A. Horwitz ◽  
K. C. Eiffert ◽  
R. B. McDonald
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Hindlimb Muscle ◽  
Glycogen Utilization ◽  
Sciatic Nerve Stimulation ◽  
Glycogen Stores ◽  
F344 Rats ◽  
Krebs Henseleit Buffer

Epinephrine (Epi)- and forskolin (FSK)-stimulated glycogenolysis of skeletal muscle was evaluated in perfused hindlimb isolated from male Fischer 344 (F344) rats, ages 6, 12, and 26 mo. Muscle glycogen stores were reduced by sciatic nerve stimulation and replenished by infusing 10 mM glucose, 500 microU insulin, and 5 microCi [14C]glucose via a left carotid artery cannula. Then the hindlimb was perfused with a modified Krebs-Henseleit buffer (pH 7.4). At minute 20 of the perfusion, Epi [0.0 (perfusate), 0.25, 0.50, or 0.75 microM] or 40 microM FSK were infused for 10 min. Radioactivity (14C) in the effluent perfusate was collected every 60 s during a 20-min preinfusion, a 10-min Epi infusion, and a 20-min postinfusion period and was used to determine the rate of muscle glycogen utilization. Total 14C release increased with Epi and 40 microM FSK. However, the pattern of release did not differ significantly with age. In general, the fraction of the perfusate released as 14CO2 increased in the presence of FSK and Epi but did not significantly differ with age. [14C]lactate released in response to Epi increased in the 6-mo-old group, remained unchanged in the 12-mo-old group, and decreased in the 26-mo-old group compared with 0.0 Epi (perfusate) values. It appears that stimulation of skeletal muscle glycogenolysis via adrenergic receptor or postreceptor/adenosine 3',5'-cyclic monophosphate-mediated mechanisms is unaffected by age. However, the utilization of carbohydrate by isolated hindlimb muscle is altered in the aging rat, resulting in a more oxidative metabolism.

Selected Contribution: Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries

2003 ◽  
Vol 95 (5) ◽  
pp. 2164-2170 ◽  
Author(s):  
Christopher R. Woodman ◽  
Elmer M. Price ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Soleus Muscle ◽  
No Synthase ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Dependent Flow ◽  
Feed Arteries

We tested the hypothesis that endothelium-dependent dilation in soleus muscle feed arteries (SFA) is impaired by aging due to attenuated nitric oxide (NO)-mediated vasodilation. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two glass micropipettes for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. Flow- and ACh-induced dilation was significantly attenuated by age, whereas dilation to SNP was not compromised. To determine the mechanism(s) by which aging affected dilator responses to flow and ACh, dilation was assessed in the presence of Nω-nitro-l-arginine (l-NNA; to inhibit NO synthase), indomethacin (Indo; to inhibit cyclooxygenase), and l-NNA + Indo. In the presence of l-NNA, Indo, or l-NNA + Indo, flow-induced dilation was inhibited in young SFA, resulting in a response to flow that was no longer greater than old SFA. In the presence of l-NNA or Indo, ACh-induced dilation was not significantly inhibited in young or old SFA; however, double blockade with l-NNA + Indo inhibited ACh-induced dilation in young SFA such that the response to ACh was no longer greater than old SFA. Collectively, these data indicate that aging impairs vasodilator responses in SFA by attenuating NO- and prostacyclin-mediated, endothelium-dependent, dilation.

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