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.

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.

The 1990 Borden Award Lecture Dietary regulation of fatty acid and triglyceride metabolism

1991 ◽  
Vol 69 (11) ◽  
pp. 1637-1647 ◽  
Author(s):  
Gene R. Herzberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipoprotein Lipase ◽  
Fatty Acid Synthesis ◽  
Dietary Fat ◽  
Acid Synthesis ◽  
Fish Oils ◽  
Dietary Fish

The level of circulating triacylglycerols is determined by the balance between their delivery into the plasma and their removal from it. Plasma triacylglycerols are derived either from dietary fat as chylomicrons or from endogenous hepatic synthesis as very low density lipoproteins. Their removal occurs through the action of lipoprotein lipase after which the fatty acids are either stored in adipose tissue or oxidized, primarily in skeletal muscle and heart. The composition of the diet has been shown to influence many of these processes. Hepatic fatty acid synthesis and triacylglycerol secretion are affected by the quantity and composition of dietary fat, carbohydrate, and protein. Polyunsaturated but not saturated fats reduce hepatic fatty acid synthesis by decreasing the amount of the lipogenic enzymes needed for de novo fatty acid synthesis. Dietary fish oils are particularly effective at reducing both fatty acid synthesis and triacylglycerol secretion and as a result are hypotriacylglycerolemic, particularly in hypertriacylglycerolemic individuals. In addition, dietary fish oils can increase the oxidation of fatty acids and lead to increased activity of lipoprotein lipase in skeletal muscle and heart. It appears that the hypotriacylglycerolemic effect of dietary fish oils is mediated by effects on both synthesis and removal of circulating triacylglycerols.Key words: lipid, fish oil, fructose, liver, adipose tissue, oxidation.

scholarly journals The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150272 ◽  
Author(s):  
Ren Zhang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
White Adipose Tissue ◽  
Skeletal Muscles ◽  
General Framework ◽  
Peripheral Tissues ◽  
Specific Regulation ◽  
Rate Limiting

Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed–fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8–Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated.

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.

2008 Robert Levy Memorial Lecture—Tissue-Specific Regulation of Lipoprotein Lipase and Energy Balance: The Story Gets Even More Interesting

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Robert Eckel
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Regulation ◽  
Body Weight Regulation ◽  
Tissue Specific ◽  
Specific Manner ◽  
The Brain

Lipoprotein lipase (LPL) is a multifunctional enzyme produced by and studied in many tissues, including adipose tissue, cardiac and skeletal muscle, islets, and macrophages. After synthesis by parenchymal cells, the lipase is transported to the capillary endothelium, where it is rate-limiting for the hydrolysis of the triglyceride (TG) core of the circulating TG-rich lipoproteins, chylomicrons, and very low density lipoproteins (VLDL). The reaction products, fatty acids and monoacylglycerol, are in part taken up by the tissues locally, where they are processed in a tissue-specific manner, e.g., stored as neutral lipids (TG > cholesteryl esters[CE]) in adipose tissue, oxidized or stored in muscle, or as CE/TG in foam cells in macrophages. LPL is regulated in a tissue-specific manner. In adipose tissue, LPL is increased by insulin and meals but decreased by fasting, whereas muscle LPL is decreased by insulin and increased by fasting. In obesity, adipose tissue LPL is increased; however, the insulin dose-response curve is shifted to the right. After weight reduction and stabilization of the reduced obese state, adipose tissue LPL is increased, as is the response of the enzyme to insulin and meals. In skeletal muscle, insulin does not stimulate LPL nor is the enzyme activity changed in obesity; however, after weight reduction, LPL in skeletal muscle is decreased by 70%. These tissue-specific changes in LPL set the stage for lipid partitioning to help explain the recidivism of obesity. 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 develop TG accumulation in muscle, develop insulin resistance, are protected from excessive weight gain, and increase their metabolic rate in the cold. When placed onto the LPL knockout and leptin deficient background, overexpression of LPL using an MCK promoter reduces obesity. Alternatively, a deletion of LPL in skeletal muscle reduces TG accumulation and increases insulin-mediated glucose transport into muscle but leads to lipid partitioning to other tissues, insulin resistance, and obesity. In the heart, loss of LPL is associated with hypertriglyceridemia and a greater utilization of glucose, implying that free fatty acids are not a sufficient fuel for optimal cardiac function. LPL is also produced in the brain, and that’s where the “story gets even more interesting.” We have just created mice with a neuron-specific deletion of LPL (NEXLPL−/−) using cre recombinase driven by the helix-loop-helix nuclear transcription factor NEX promoter. By 6 months of age, NEXLPL−/− mice weigh 50% more than their litter mates. This phenotype provides convincing evidence that lipoprotein sensing occurs in the brain and is important to energy balance and body weight regulation. Overall, LPL is a fascinating enzyme that contributes in a pronounced way to normal lipoprotein metabolism, tissue-specific substrate delivery and utilization, and to the many aspects of metabolism that relate to cardiovascular disease, including energy metabolism, insulin action, body weight regulation, and atherosclerosis.

Prevention of diet-induced obesity in transgenic mice overexpressing skeletal muscle lipoprotein lipase

1997 ◽  
Vol 273 (2) ◽  
pp. R683-R689 ◽  
Author(s):  
D. R. Jensen ◽  
I. R. Schlaepfer ◽  
C. L. Morin ◽  
D. S. Pennington ◽  
T. Marcell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Lipid Content ◽  
High Fat ◽  
Muscle Creatine Kinase ◽  
Plasma Triglycerides ◽  
Diet Induced Obesity ◽  
Fat Feeding

Transgenic (Tg) FVB/N mice were produced that overexpress human lipoprotein lipase (LPL) in skeletal muscle using the muscle creatine kinase promoter and enhancers. It was hypothesized that, by overexpressing LPL in muscle, high fat feeding-induced obesity would be prevented by diverting lipoprotein-derived triglyceride fatty acids away from storage in adipose tissue to oxidation in muscle. Mice were examined both at 6 wk of age before high fat (HF) feeding and at 19 wk of age after 13 wk of HF (46.1% fat) or high carbohydrate (HC) feeding (11.5% fat). At 6 wk in heterozygous Tg mice, LPL was increased 11-fold in white muscle and 2.5-fold in red muscle, but not in cardiac muscle or spleen, brain, lung, kidney, or adipose tissue. Plasma triglycerides (mg/dl) were lower in Tg mice (87 +/- 7 vs. 117 +/- 7, P < 0.0001), and glucose increased (201 +/- 9 vs. 167 +/- 8 mg/dl, P = 0.029). There were no differences in body weight between Tg and nontransgenic (nTg) mice; however, carcass lipid content (% body wt) was significantly decreased in male Tg mice at 6 wk (7.5 +/- 1.0 vs. 9.0 +/- 1.0%, P = 0.035). Body composition was not different in female Tg mice at 6 wk. Overall, when Tg mice were fed either a HC or HF diet for 13 wk, plasma triglycerides (P < 0.001) and free fatty acids (P < 0.001) were decreased, whereas plasma glucose (P = 0.01) and insulin (P = 0.05) were increased compared with nTg mice. HF feeding increased carcass lipid content twofold in both male (10.3 +/- 1.1 vs. 21.4 +/- 2.6%, HC vs. HF, P < 0.001) and female nTg mice (6.7 +/- 0.9 vs. 12.9 +/- 1.8%, P = 0.01). However, the targeted overexpression of LPL in skeletal muscle prevented HF diet-induced lipid accumulation in both Tg male (10.2 +/- 0.7 vs. 13.5 +/- 2.2%, HC vs. HF, P = NS) and female Tg mice (6.8 +/- 0.6 vs. 10.1 +/- 1.4%, P = NS). The potential to increase LPL activity in muscle by gene or drug delivery may prove to be an effective tool in preventing and/or treating obesity in humans.

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

Adipose tissue in experimental nephrotic syndrome

1963 ◽  
Vol 205 (4) ◽  
pp. 702-706 ◽  
Author(s):  
Alisa Gutman ◽  
Eleazar Shafrir
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Nephrotic Syndrome ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Lipoprotein Lipase ◽  
Epididymal Adipose Tissue ◽  
Adequate Nutrition ◽  
Defective Metabolism ◽  
Inadequate Food Intake

Epididymal adipose tissue of aminonucleoside-treated rats, investigated 3 to 6 days after induction of the nephrotic syndrome, had low glycogen levels and showed impaired esterification of free fatty acids and assimilation of lipoprotein triglyceride and markedly reduced liberation of lipoprotein lipase. These results were found to be influenced by the inadequate food intake of the acutely nephrotic animals and comparable to the values of control rats fasted for 2 days. On return to adequate nutrition, which occurred 12–20 days after aminonucleoside treatment, adipose tissue glycogen and free fatty acid assimilation returned toward normal levels but lipoprotein-lipase liberation remained below normal. In rats rendered nephrotic by antikidney serum, the assimilation of free fatty acids and lipoprotein-triglyceride by adipose tissue was impaired in spite of only minor reduction in food consumption. The results indicate that the defective metabolism of adipose tissue in nephrotic animals may be contributory to the nephrotic hypertriglyceridemia.

Serum Activation of Lipoprotein Lipase from Sheep Adipose Tissue

1985 ◽  
Vol 38 (1) ◽  
pp. 131
Author(s):  
RK Tume ◽  
RF Thornton
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Lipoprotein Lipase Activity ◽  
Nutritional Restriction ◽  
Adipose Tissue Lipoprotein Lipase ◽  
Increased Activity ◽  
Substrate Concentrations

The effects of species and plane of nutrition on serum activation of sheep adipose tissue lipoprotein lipase were studied over a range of substrate (triolein) concentrations. Serum, either from two species or from the same species on a different plane of nutrition, had differing effects on adipose tissue lipoprotein lipase activity. Serum from fed sheep was more effective than serum from fed rats in activating sheep adipose tissue lipoprotein lipase at low substrate concentrations. Serum taken from sheep on a restricted plane of nutrition, stimulated adipose tissue lipoprotein lipase activity at physiological substrate concentrations. The increased activity promoted by the factor(s) present in serum would ensure that those tissues (e.g. cardiac and skeletal muscle) which continue to synthesize lipoprotein lipase during fasting or nutritional restriction, are able to assimilate the relatively low amounts of circulating triacylglycerol.

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