scholarly journals Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased α-tocopherol levels in skeletal muscle

1996 ◽  
Vol 318 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Wolfgang SATTLER ◽  
Sanja LEVAK-FRANK ◽  
Herbert RADNER ◽  
Gerhard M. KOSTNER ◽  
Rudolf ZECHNER
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Cardiac Muscle ◽  
Lipoprotein Lipase ◽  
Excellent Correlation ◽  
Peripheral Tissues ◽  
Tissue Specific

Lipoprotein lipase (LPL) has been implicated in the delivery of chylomicron-located α-tocopherol (α-TocH) to peripheral tissues. To investigate the role of LPL in the cellular uptake of α-TocH in peripheral tissue in vivo, three lines of transgenic mice [mouse creatine kinase- (MCK) L, MCK-M and MCK-H] expressing various amounts of human LPL were compared with regard to α-TocH levels in plasma, skeletal muscle, cardiac muscle, adipose tissue and brain. Depending on the copy number of the transgene, LPL activity was increased 3- to 27-fold in skeletal muscle and 1.3- to 3.7-fold in cardiac muscle. The intracellular levels of α-TocH in skeletal muscle were significantly increased in MCK-M and MCK-H animals and correlated highly with the tissue-specific LPL activity (r = 0.998). The highest levels were observed in MCK-H (21.4 nmol/g) followed by MCK-M (13.3 nmol/g) and MCK-L (8.2 nmol/g) animals when compared with control mice (7.3 nmol/g). Excellent correlation was also observed between intracellular α-TocH and non-esterified fatty acid (NEFA) levels (r = 0.998). Although LPL activities in cardiac muscle were also increased in the transgenic mouse lines, α-TocH concentrations in the heart remained unchanged. Similarly, α-TocH levels in plasma, adipose tissue and brain were unaffected by the tissue specific overexpression of LPL in muscle. The transgenic model presented in this report provides evidence that the uptake of α-TocH in muscle is directly dependent on the level of LPL expression in vivo. Increased intracellular α-TocH concentrations with increased triglyceride lipolysis and NEFA uptake might protect the myocyte from oxidative damage during increased β-oxidation.

In vitro and in vivo analysis of murine lipoprotein lipase gene promoter: tissue-specific expression

1995 ◽  
Vol 268 (2) ◽  
pp. E213-E218 ◽  
Author(s):  
J. M. Gimble ◽  
X. Hua ◽  
F. Wanker ◽  
C. Morgan ◽  
C. Robinson ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Lipoprotein Lipase ◽  
Reporter Gene ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Specific Expression ◽  
Tissue Specific ◽  
Brown Adipose ◽  
Octamer Motif

Lipoprotein lipase, an enzyme of central importance to lipid metabolism, is most abundant in adipose tissues, cardiac and skeletal muscle, and portions of the brain. The current work examined the murine lipoprotein lipase promoter using transient transfection, gel-retention analyses, and transgenic mice. Maximum expression of the luciferase reporter gene in transfected cells was observed with -101 bp of the promoter. Nuclear extracts from tissues expressing lipoprotein lipase contained DNA binding proteins that recognize the CCAAT box (-64 bp) and an octamer motif (-46 bp); this combination of factors was absent in nonexpressing tissues. Transgenic mice from three of five founders prepared with -1,824-bp promoter constructs expressed the luciferase reporter gene at highest levels in brown adipose tissue and brain. These findings suggest that the -1,824-bp promoter region contains sequence elements responsible for the tissue-specific transcription of lipoprotein lipase in vivo.

scholarly journals CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction

2013 ◽  
Vol 305 (5) ◽  
pp. R522-R533 ◽  
Author(s):  
Jonathan M. Peterson ◽  
Zhikui Wei ◽  
Marcus M. Seldin ◽  
Mardi S. Byerly ◽  
Susan Aja ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
High Fat Diet ◽  
Fat Oxidation ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
High Fat ◽  
Diet Induced Obesity

CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin. The metabolic function of this adipose tissue-derived plasma protein remains largely unknown. Here, we show that the circulating levels of CTRP9 are downregulated in diet-induced obese mice and upregulated upon refeeding. Overexpressing CTRP9 resulted in lean mice that dramatically resisted weight gain induced by a high-fat diet, largely through decreased food intake and increased basal metabolism. Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation. Hepatic and skeletal muscle triglyceride levels were substantially decreased in transgenic mice. Consequently, CTRP9 transgenic mice had a greatly improved metabolic profile with markedly reduced fasting insulin and glucose levels. The high-fat diet-induced obesity, insulin resistance, and hepatic steatosis observed in wild-type mice were prevented in transgenic mice. Consistent with the in vivo data, recombinant protein significantly enhanced fat oxidation in L6 myotubes via AMPK activation and reduced lipid accumulation in H4IIE hepatocytes. Collectively, these data establish CTRP9 as a novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver.

Lipoprotein lipase: from gene to obesity

2009 ◽  
Vol 297 (2) ◽  
pp. E271-E288 ◽  
Author(s):  
Hong Wang ◽  
Robert H. Eckel
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Insulin Action ◽  
Specific Activity ◽  
Neutral Lipids ◽  
Specific Substrate ◽  
Tissue Specific

Lipoprotein lipase (LPL) is a multifunctional enzyme produced by many tissues, including adipose tissue, cardiac and skeletal muscle, islets, and macrophages. LPL is the rate-limiting enzyme for the hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins, chylomicrons, and very low-density lipoproteins (VLDL). LPL-catalyzed reaction products, fatty acids, and monoacylglycerol are in part taken up by the tissues locally and processed differentially; e.g., they are stored as neutral lipids in adipose tissue, oxidized, or stored in skeletal and cardiac muscle or as cholesteryl ester and TG in macrophages. LPL is regulated at transcriptional, posttranscriptional, and posttranslational levels in a tissue-specific manner. Nutrient states and hormonal levels all have divergent effects on the regulation of LPL, and a variety of proteins that interact with LPL to regulate its tissue-specific activity have also been identified. To examine this divergent regulation further, transgenic and knockout murine models of tissue-specific LPL expression have been developed. Mice with overexpression of LPL in skeletal muscle accumulate TG in muscle, develop insulin resistance, are protected from excessive weight gain, and increase their metabolic rate in the cold. Mice with LPL deletion in skeletal muscle have reduced TG accumulation and increased insulin action on glucose transport in muscle. Ultimately, this leads to increased lipid partitioning to other tissues, insulin resistance, and obesity. Mice with LPL deletion in the heart develop hypertriglyceridemia and cardiac dysfunction. The fact that the heart depends increasingly on glucose implies that free fatty acids are not a sufficient fuel for optimal cardiac function. Overall, LPL is a fascinating enzyme that contributes in a pronounced way to normal lipoprotein metabolism, tissue-specific substrate delivery and utilization, and the many aspects of obesity and other metabolic disorders that relate to energy balance, insulin action, and body weight regulation.

scholarly journals Tissue-specific changes in the ability of insulin and noradrenaline to activate pyruvate dehydrogenase in vivo during lactation in the rat

1987 ◽  
Vol 243 (1) ◽  
pp. 69-74 ◽  
Author(s):  
E Kilgour ◽  
R G Vernon
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Mammary Gland ◽  
White Adipose Tissue ◽  
Pyruvate Dehydrogenase ◽  
Active State ◽  
The Other ◽  
Tissue Specific ◽  
Preferential Utilization

Changes are described in the total pyruvate dehydrogenase (PDH) activity, the proportion of PDH in the active state and its control by insulin and noradrenaline in vivo, in white adipose tissue, liver, skeletal muscle and mammary gland with pregnancy, lactation and on weaning. Lactation resulted in a decrease in total PDH in white adipose tissue and an increase in the mammary gland, whereas the proportion in the active state decreased in muscle and increased in the mammary gland. The ability of insulin to activate PDH of white adipose tissue was lost during lactation, whereas it was retained by the other tissues. The ability of noradrenaline to activate PDH was decreased in white adipose tissue but increased in liver during lactation. These various adaptations should limit the use of glucose and lactate carbon by adipose tissue and skeletal muscle during lactation and thereby facilitate their preferential utilization by the mammary gland.

scholarly journals Lmo7 is dispensable for skeletal muscle and cardiac function

2015 ◽  
Vol 309 (7) ◽  
pp. C470-C479 ◽  
Author(s):  
Dieu Hung Lao ◽  
Mary C. Esparza ◽  
Shannon N. Bremner ◽  
Indroneal Banerjee ◽  
Jianlin Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Cardiac Function ◽  
Cardiac Muscle ◽  
Mapk Pathway ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Mouse Line

Emery-Dreifuss muscular dystrophy (EDMD) is a degenerative disease primarily affecting skeletal muscles in early childhood as well as cardiac muscle at later stages. EDMD is caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Emerin, Lamin A/C, and Nesprin). Recently, a novel protein, Lim-domain only 7 ( lmo7) has been reported to play a role in the molecular pathogenesis of EDMD. Prior in vitro and in vivo studies suggested the intriguing possibility that Lmo7 plays a role in skeletal or cardiac muscle pathophysiology. To further understand the in vivo role of Lmo7 in striated muscles, we generated a novel Lmo7-null ( lmo7−/−) mouse line. Using this mouse line, we examined skeletal and cardiac muscle physiology, as well as the role of Lmo7 in a model of muscular dystrophy and regeneration using the dystrophin-deficient mdx mouse model. Our results demonstrated that lmo7−/− mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. Cardiac function was also unaffected. Moreover, we found that ablation of lmo7 in mdx mice had no effect on the observed myopathy and muscular regeneration exhibited by mdx mice. Molecular analyses also showed no changes in dystrophin complex factors, MAPK pathway components, and Emerin levels in lmo7 knockout mice. Taken together, we conclude that Lmo7 is dispensable for skeletal muscle and cardiac physiology and pathophysiology.

scholarly journals Microdialysis: use in human exercise studies

1999 ◽  
Vol 58 (4) ◽  
pp. 913-917 ◽  
Author(s):  
Peter Arner
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Brain Function ◽  
Water Soluble ◽  
Tissue Blood Flow ◽  
Microdialysis Probe ◽  
Peripheral Tissues

Microdialysis has been used for 25 years to study brain function in vivo. Recently, it has been developed for investigations on peripheral tissues. A microdialysis catheter is an artificial blood vessel system which can be placed in the extracellular space of various tissues such as adipose tissue and skeletal muscle in order to examine these tissues in situ. Molecules are collected from the tissue by the device and their true interstitial concentration can be estimated. Metabolically-active molecules can be delivered to the interstitial space through the microdialysis probe and their action on the tissue can be investigated locally without producing generalized effects. It is also possible to study local tissue blood flow with microdialysis by adding a flow marker (usually ethanol) to the microdialysis solvent. The microdialysis technique is particularly useful for studies of small and water-soluble molecules. A number of important observations on the in vivo regulation of lipolysis, carbohydrate metabolism and blood flow in human skeletal muscle and adipose tissue have been made recently using microdialysis.

Periprandial systemic and regional lipase activity in normal humans

1996 ◽  
Vol 270 (4) ◽  
pp. E718-E722 ◽  
Author(s):  
S. W. Coppack ◽  
T. J. Yost ◽  
R. M. Fisher ◽  
R. H. Eckel ◽  
J. M. Miles
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Tissue Level ◽  
Normal Male ◽  
Arterial Plasma ◽  
Subcutaneous Abdominal Adipose Tissue ◽  
Subcutaneous Adipose

An assay for plasma lipoprotein lipase activity was used without prior injection of heparin to study arteriovenous differences of lipases across skeletal muscle and adipose tissue of normal male volunteers. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and triglyceride?concentrations were measured in arterial plasma and in venous effluent plasma from forearm skeletal muscle and subcutaneous abdominal adipose tissue, in the postabsorptive state and after a mixed meal. Triglyceride clearance by the tissues was greater across adipose tissue than across muscle. There were no arteriovenous differences for HTGL activity. In the postabsorptive state skeletal muscle released LPL activity, but adipose tissue did not. Postprandially the arterial LPL and HTGL activities did not change. LPL activity in adipose tissue venous effluent rose, whereas that in muscle venous effluent decreased. These results show that the release of LPL from subcutaneous adipose and forearm tissues is regulated differently, reflecting in vivo differences in LPL regulation at the tissue level.

Tissue-specific regulation of lipoprotein lipase by isoproterenol in normal-weight humans

1996 ◽  
Vol 271 (5) ◽  
pp. R1280-R1286 ◽  
Author(s):  
R. H. Eckel ◽  
D. R. Jensen ◽  
I. R. Schlaepfer ◽  
T. J. Yost
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Plasma Norepinephrine ◽  
Vastus Lateralis Muscle ◽  
Specific Response ◽  
Tissue Specific ◽  
Percent Change ◽  
Specific Regulation

Lipoprotein lipase (LPL) is a hydrolytic enzyme, involved in lipoprotein metabolism and nutrient partitioning, that is subject to tissue-specific regulation. Evidence for divergent regulation of the lipase by insulin has been demonstrated, but alterations in the tissue-specific response of LPL to catecholamines has not been studied in humans. The regulation of LPL in gluteal adipose tissue and vastus lateralis muscle by isoproterenol (epinephrine isopropyl homologue) in humans was examined over 2 h in subjects infused with 0 (saline) or 8 or 24 ng.kg-1.min-1 isoproterenol. The infusion of normal saline into control subjects failed to alter adipose tissue or skeletal muscle LPL activity. However, in the saline-infused subjects there was a positive correlation between the percent change in plasma norepinephrine concentrations and the percent change in muscle LPL activity (r = 0.826, P < 0.05). Isoproterenol infusion did not change LPL in either adipose tissue or muscle compared with saline-infused controls, but plasma insulin levels in addition to plasma glucose, free fatty acids, and glycerol were increased. To prevent the isoproterenol-induced hyperinsulinemia, a pancreatic clamp technique was utilized. An increase in muscle LPL was demonstrated (P = 0.037) with no change in adipose tissue LPL. The change in muscle LPL activity after the 2-h infusion correlated with the change in muscle mRNA (P = 0.021). Overall, these studies indicate that in humans the response of LPL to catecholamines is tissue specific with no effect in adipose tissue but a stimulation in skeletal muscle. Endogenous regulation of LPL in muscle by catecholamines could be important in muscle fuel metabolism and could relate to effects of adenosine 3',5'-cyclic monophosphate and/or fatty acids at the level of the LPL gene.

Effect of a β3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro

1993 ◽  
Vol 139 (3) ◽  
pp. 479-486 ◽  
Author(s):  
H. Abe ◽  
Y. Minokoshi ◽  
T. Shimazu
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Plasma Concentration ◽  
Glucose Uptake ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Brown Adipose ◽  
Dose Dependent

ABSTRACT The effects of the β3-agonist, BRL35135A, on glucose uptake in the peripheral tissues of the rat, including skeletal muscle, were studied using the 2-[3H]deoxyglucose method in anaesthetized adult animals. Intravenous infusion of the β3-agonist dose-dependently increased the rate constant of glucose uptake in three types of skeletal muscle, brown adipose tissue, white adipose tissue, heart and diaphragm, but not in the brain, spleen or lung. Although infusion of the β3-agonist did not change the plasma concentration of glucose appreciably, it caused an increase in the plasma concentration of insulin when given at more than 25 μg/kg per h. To ascertain whether the effect of the β3-agonist on glucose uptake in skeletal muscle is mediated by insulin, glucose uptake into soleus muscle isolated from young rats was also measured in vitro using different concentrations of the β3-agonist. The β3-agonist BRL37344 (an active metabolite of BRL35135A) significantly increased glucose transport in a dose-dependent manner, with maximum stimulation at 100 pmol/l. These results demonstrate that glucose uptake in skeletal muscle can be enhanced independently of the action of insulin, probably through the mediation of β3-adrenoceptors present in the tissue. Journal of Endocrinology (1993) 139, 479–486

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