Plasma Triglyceride Metabolism in Humans and Rats during Aging and Physical Inactivity

2001 ◽  
Vol 11 (s1) ◽  
pp. S97-S102 ◽  
Author(s):  
Marc T. Hamilton ◽  
Enas Areiqat ◽  
Deborah G. Hamilton ◽  
Lionel Bey

Physical activity often declines with age because of a reduction in the spontaneous activities of daily living and because of less intense exercise. In controlled studies of young rats, it was shown that physical activities associated with walking and standing were especially important for maintaining a high level of lipoprotein lipase (LPL) activity in postural skeletal muscles (slowtwitch oxidative muscles). More intense contractions during run training were important for a high LPL activity in the fast-twitch glycolytic muscles. Aging also causes a fiber type–specific decrease of skeletal muscle LPL activity and LPL protein in weight-bearing skeletal muscles (and no aging effect in glycolytic muscles). Thus, contractile inactivity may be a significant factor causing sub-optimal triglyceride metabolism in skeletal muscles during both unloading in young animals and aging. Measurements of plasma LPL activity, plasma triglyceride (TG) clearance rates, postprandial hypertriglyceridemia after oral fat tolerance tests, and fasting TG levels were generally indicative of reduced plasma TG metabolism during middle or old age. In contrast, older endurance-trained individuals had a favorable blood lipid profile compared to age-matched or young controls, even when the controls were not overweight. Therefore, the poor TG metabolism that is frequently associated with aging may be caused by some of the same processes that lower skeletal muscle LPL activity of young sedentary individuals.

2018 ◽  
Vol 28 (1) ◽  
Author(s):  
Ugo Carraro

Myologists working in Padua (Italy) were able to continue a half-century tradition of studies of skeletal muscles, that started with a research on fever, specifically if and how skeletal muscle contribute to it by burning bacterial toxin. Beside main publications in high-impact-factor journals by Padua myologists, I hope to convince readers (and myself) of the relevance of the editing Basic and Applied Myology (BAM), retitled from 2010 European Journal of Translational Myology (EJTM), of the institution of the Interdepartmental Research Center of Myology of the University of Padova (CIR-Myo), and of a long series of International Conferences organized in Euganei Hills and Padova, that is, the PaduaMuscleDays. The 2018Spring PaduaMuscleDays (2018SpPMD), were held in Euganei Hills and Padua (Italy), in March 14-17, and were dedicated to Giovanni Salviati. The main event of the “Giovanni Salviati Memorial”, was held in the Aula Guariento, Accademia Galileiana di Scienze, Lettere ed Arti of Padua to honor a beloved friend and excellent scientist 20 years after his premature passing. Using the words of Prof. Nicola Rizzuto, we all share his believe that Giovanni “will be remembered not only for his talent and originality as a biochemist, but also for his unassuming and humanistic personality, a rare quality in highly successful people like Giovanni. The best way to remember such a person is to gather pupils and colleagues, who shared with him the same scientific interests and ask them to discuss recent advances in their own fields, just as Giovanni have liked to do”. Since Giovanni’s friends sent many abstracts still influenced by their previous collaboration with him, all the Sessions of the 2018SpPMD reflect both to the research aims of Giovanni Salviati and the traditional topics of the PaduaMuscleDays, that is, basics and applications of physical, molecular and cellular strategies to maintain or recover functions of skeletal muscles. The translational researches summarized in the 2018SpPMD Abstracts are at the appropriate high level to attract approval of Ethical Committees, the interest of International Granting Agencies and approval for publication in top quality, international journals. The abstracts of the March 16, 2018 Padua Muscle Day are listed in this chapter III. All 2018SpPMD Abstracts are indexed at the end of the Chapter IV.


1999 ◽  
Vol 277 (2) ◽  
pp. R601-R606 ◽  
Author(s):  
Christian J. Carlson ◽  
Frank W. Booth ◽  
Scott E. Gordon

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.


2002 ◽  
Vol 92 (3) ◽  
pp. 1145-1151 ◽  
Author(s):  
Cristine L. Heaps ◽  
Douglas K. Bowles

Hindlimb unweighting (HLU) has been shown to alter myogenic tone distinctly in arterioles isolated from skeletal muscles composed predominantly of fast-twitch (white gastrocnemius) compared with slow-twitch (soleus) fibers. Based on these findings, we hypothesized that HLU would alter myogenic tone differently in arterioles isolated from distinct fiber-type regions within a single skeletal muscle. We further hypothesized that alterations in myogenic tone would be associated with alterations in voltage-gated Ca2+ channel current (VGCC) density of arteriolar smooth muscle. After 14 days of HLU or weight bearing (control), first-order arterioles were isolated from both fast-twitch and mixed fiber-type regions of the gastrocnemius muscle, cannulated, and pressurized at 90 cmH2O. Mixed gastrocnemius arterioles of HLU rats demonstrated increased spontaneous tone [43 ± 5% (HLU) vs. 27 ± 4% (control) of possible constriction] and an approximately twofold enhanced myogenic response when exposed to step changes in intraluminal pressure (10–130 cmH2O) compared with control rats. In contrast, fast-twitch gastrocnemius arterioles of HLU rats demonstrated similar levels of spontaneous tone [6 ± 2% (HLU) vs. 6 ± 2% (control)] and myogenic reactivity to control rats. Neither KCl-induced contractile responses (10–50 mM KCl) nor VGCC density was significantly different between mixed gastrocnemius arterioles of HLU and control rats. These results suggest that HLU produces diverse adaptations in myogenic reactivity of arterioles isolated from different fiber-type regions of a single skeletal muscle. Furthermore, alterations in myogenic responses were not attributable to altered VGCC density.


2018 ◽  
Vol 28 (1) ◽  
Author(s):  
Ugo Carraro

Myologists working in Padua (Italy) were able to continue a half-century tradition of studies of skeletal muscles, that started with a research on fever, specifically if and how skeletal muscle contribute to it by burning bacterial toxin. Beside main publications in high-impact-factor journals by Padua myologists, I hope to convince readers (and myself) of the relevance of the editing Basic and Applied Myology (BAM), retitled from 2010 European Journal of Translational Myology (EJTM), of the institution of the Interdepartmental Research Center of Myology of the University of Padova (CIR-Myo), and of a long series of International Conferences organized in Euganei Hills and Padova, that is, the PaduaMuscleDays. The 2018Spring PaduaMuscleDays (2018SpPMD), were held in Euganei Hills and Padua (Italy), in March 14-17, and were dedicated to Giovanni Salviati. The main event of the “Giovanni Salviati Memorial”, was held in the Aula Guariento, Accademia Galileiana di Scienze, Lettere ed Arti of Padua to honor a beloved friend and excellent scientist 20 years after his premature passing. Using the words of Prof. Nicola Rizzuto, we all share his believe that Giovanni “will be remembered not only for his talent and originality as a biochemist, but also for his unassuming and humanistic personality, a rare quality in highly successful people like Giovanni. The best way to remember such a person is to gather pupils and colleagues, who shared with him the same scientific interests and ask them to discuss recent advances in their own fields, just as Giovanni have liked to do”. Since Giovanni’s friends sent many abstracts still influenced by their previous collaboration with him, all the Sessions of the 2018SpPMD reflect both to the research aims of Giovanni Salviati and the traditional topics of the PaduaMuscleDays, that is, basics and applications of physical, molecular and cellular strategies to maintain or recover functions of skeletal muscles. The translational researches summarized in the 2018SpPMD Abstracts are at the appropriate high level to attract approval of Ethical Committees, the interest of International Granting Agencies and approval for publication in top quality, international journals. In this chapter IV are included the abstracts of the presentations of the March 16, 2018 Padua Muscle Day, those of the remaining Posters and the complete Index of Authors.


1990 ◽  
Vol 259 (4) ◽  
pp. E517-E523 ◽  
Author(s):  
D. J. Koerker ◽  
I. R. Sweet ◽  
D. G. Baskin

Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding.


2020 ◽  
Vol 295 (15) ◽  
pp. 4937-4949 ◽  
Author(s):  
Mingle Dou ◽  
Ying Yao ◽  
Lu Ma ◽  
Xiaoyu Wang ◽  
Xin'e Shi ◽  
...  

Mammalian skeletal muscles comprise different types of muscle fibers, and this muscle fiber heterogeneity is generally characterized by the expression of myosin heavy chain (MyHC) isoforms. A switch in MyHC expression leads to muscle fiber–type transition under various physiological and pathological conditions, but the underlying regulator coordinating the switch of MyHC expression remains largely unknown. Experiments reported in this study revealed the presence of a skeletal muscle–specific antisense transcript generated from the intergenic region between porcine MyHC IIa and IIx and is referred to here as MyHC IIA/X-AS. We found that MyHC IIA/X-AS is identified as a long noncoding RNA (lncRNA) that is strictly expressed in skeletal muscles and is predominantly distributed in the cytoplasm. Genetic analysis disclosed that MyHC IIA/X-AS stimulates cell cycle exit of skeletal satellite cells and their fusion into myotubes. Moreover, we observed that MyHC IIA/X-AS is more enriched in fast-twitch muscle and represses slow-type gene expression and thereby maintains the fast phenotype. Furthermore, we found that MyHC IIA/X-AS acts as a competing endogenous RNA that sponges microRNA-130b (miR-130b) and thereby maintains MyHC IIx expression and the fast fiber type. We also noted that miR-130b was proved to down-regulate MyHC IIx by directly targeting its 3′-UTR. Together, the results of our study uncovered a novel pathway, which revealed that lncRNA derived from the skeletal MyHC cluster could modulate local MyHC expression in trans, highlighting the role of lncRNAs in muscle fiber–type switching.


2004 ◽  
Vol 5 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Alissa Guildner Gehrke ◽  
Margaret Sheie Krull ◽  
Robin Shotwell McDonald ◽  
Tracy Sparby ◽  
Jessica Thoele ◽  
...  

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.


2020 ◽  
Vol 21 (18) ◽  
pp. 6480 ◽  
Author(s):  
Eyal Bengal ◽  
Sharon Aviram ◽  
Tony Hayek

Skeletal muscles respond to environmental and physiological changes by varying their size, fiber type, and metabolic properties. P38 mitogen-activated protein kinase (MAPK) is one of several signaling pathways that drive the metabolic adaptation of skeletal muscle to exercise. p38 MAPK also participates in the development of pathological traits resulting from excessive caloric intake and obesity that cause metabolic syndrome and type 2 diabetes (T2D). Whereas p38 MAPK increases insulin-independent glucose uptake and oxidative metabolism in muscles during exercise, it contrastingly mediates insulin resistance and glucose intolerance during metabolic syndrome development. This article provides an overview of the apparent contradicting roles of p38 MAPK in the adaptation of skeletal muscles to exercise and to pathological conditions leading to glucose intolerance and T2D. Here, we focus on the involvement of p38 MAPK in glucose metabolism of skeletal muscle, and discuss the possibility of targeting this pathway to prevent the development of T2D.


2006 ◽  
Vol 291 (2) ◽  
pp. C203-C217 ◽  
Author(s):  
Aaron G. Smith ◽  
George E. O. Muscat

Nuclear hormone receptors (NRs) are ligand-dependent transcription factors that bind DNA and translate physiological signals into gene regulation. The therapeutic utility of NRs is underscored by the diversity of drugs created to manage dysfunctional hormone signaling in the context of reproductive biology, inflammation, dermatology, cancer, and metabolic disease. For example, drugs that target nuclear receptors generate over $10 billion in annual sales. Almost two decades ago, gene products were identified that belonged to the NR superfamily on the basis of DNA and protein sequence identity. However, the endogenous and synthetic small molecules that modulate their action were not known, and they were denoted orphan NRs. Many of the remaining orphan NRs are highly enriched in energy-demanding major mass tissues, including skeletal muscle, brown and white adipose, brain, liver, and kidney. This review focuses on recently adopted and orphan NR function in skeletal muscle, a tissue that accounts for ∼35% of the total body mass and energy expenditure, and is a major site of fatty acid and glucose utilization. Moreover, this lean tissue is involved in cholesterol efflux and secretes that control energy expenditure and adiposity. Consequently, muscle has a significant role in insulin sensitivity, the blood lipid profile, and energy balance. Accordingly, skeletal muscle plays a considerable role in the progression of dyslipidemia, diabetes, and obesity. These are risk factors for cardiovascular disease, which is the the foremost cause of global mortality (>16.7 million deaths in 2003). Therefore, it is not surprising that orphan NRs and skeletal muscle are emerging as therapeutic candidates in the battle against dyslipidemia, diabetes, obesity, and cardiovascular disease.


1992 ◽  
Vol 119 (4) ◽  
pp. 811-821 ◽  
Author(s):  
D Houzelstein ◽  
G E Lyons ◽  
J Chamberlain ◽  
M E Buckingham

The spatial and temporal expression of the dystrophin gene has been examined during mouse embryogenesis, using in situ hybridization on tissue sections with a probe from the 5' end of the dystrophin coding sequence. In striated muscle, dystrophin transcripts are detectable from about 9 d in the heart and slightly later in skeletal muscle. However, there is an important difference between the two types of muscle: the heart is already functional as a contractile organ before the appearance of dystrophin transcripts, whereas this is not the case in skeletal muscle, where dystrophin and myosin heavy chain transcripts are first detectable at the same time. In the heart, dystrophin transcripts accumulate initially in the outflow tract and, at later stages, in both the atria and ventricles. In skeletal muscle, the gene is expressed in all myocytes irrespective of fiber type. In smooth muscle dystrophin transcripts are first detectable from 11 d post coitum in blood vessels, and subsequently in lung bronchi and in the digestive tract. The other major tissue where the dystrophin gene is expressed is the brain, where transcripts are clearly detectable in the cerebellum from 13 d. High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context. The findings are discussed in the context of the pathology of Duchenne muscular dystrophy.


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