Increased lipoprotein lipase activity of skeletal muscle in cold-acclimated rats

The activity of lipoprotein lipase (LPL) in the heart, diaphragm, and soleus muscles was markedly increased in cold-acclimated rats and it was even greater in rats treated with oxytetracycline (OTC) while exposed to cold. Other skeletal muscles studied had low and variable activities which were not significantly increased by cold acclimation or by cold plus OTC treatment. It appears therefore that, apart from the heart and the muscles involved in respiratory movements, LPL activity is primarily associated with those muscles which contain a predominance of slow-twitch oxidative fibers, and that the enzyme in muscle, heart, and diaphragm responds to cold acclimation and cold plus OTC treatment in a parallel fashion in these tissues.     

Time course of changes in lipoprotein lipase activity in rat skeletal muscles during denervation-reinnervation.

The effects of denervation-reinnervation after sciatic nerve crush on the activity of extracellular and intracellular lipoprotein lipase (LPL) were examined in the soleus and red portion of gastrocnemius muscles. The activity of both LPL fractions was decreased in the two muscles within 24 h after the nerve crush and remained reduced for up to 2 wk. During the reinnervation period, LPL activity was still reduced in the soleus and started to increase only on the 40th day. In the red gastrocnemius, LPL activity increased progressively with reinnervation, exceeding control values on the 30th day post-crush. The LPL activity in the soleus from the contralateral to denervated hindlimb was also affected, being increased on the postoperation day and then gradually decreased during the following days. In conclusion, the time course of changes in muscle LPL activity after nerve crush confirmed the predominant role of nerve conduction in controlling muscle potential to take up free fatty acids derived from the plasma triacylglycerols. However, other factors, such as muscle fiber composition and the fiber transformation, should also be considered in this aspect of the denervation-reinnervation process. Moreover, it was found that denervation of muscles from one hindlimb may influence LPL activity in muscles from the contralateral leg.     

Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity.

Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-alpha, inducible nitric oxide synthase, and NF-kappaB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was approximately 90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects.     

Developmental changes in the activity of lipoprotein lipase (clearing-factor lipase) in rat lung, cardiac muscle, skeletal muscle and brown adipose tissue.

The lipoprotein lipase activity of the lung, skeletal muscle, heart muscle and brown adipose tissue of the rat was studied during the period from late foetal to adult life. The enzyme activity in all four tissues emerged substantially during the first 24th after birth. Subsequently, heart and lung enzyme activity remained relatively constant per unit wet weight of tissue. The enzyme activity present in brown adipose tissue and skeletal muscle was elevated per unit weight of tissue during suckling compared with other periods of life. Delivery of near-term foetuses stimulated the emergence of enzyme activity in all four tissues with the same time course as that evoked by normal delivery. The significance of the presence of the enzyme in the tissues and the activity changes which occurred during development are discussed in relation to possible mechanisms of control.     

Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise.

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerols (IMTGs), but HSL regulation is poorly understood in skeletal muscle. The present study measured human skeletal muscle HSL activity at rest and during 120 min of cycling at 60% of peak O2 uptake. Several putative HSL regulators were also measured, including muscle long-chain fatty acyl-CoA (LCFA CoA) and free AMP contents and plasma epinephrine and insulin concentrations. HSL activity increased from resting levels by 10 min of exercise (from 2.09 +/- 0.19 to 2.56 +/- 0.22 mmol. min-1x kg dry mass-1, P < 0.05), increased further by 60 min (to 3.12 +/- 0.27 mmol x min-1x kg dry mass-1, P < 0.05), and decreased to near-resting rates after 120 min of cycling. Skeletal muscle LCFA CoA increased (P < 0.05) above rest by 60 min (from 15.9 +/- 3.0 to 50.4 +/- 7.9 micromol/kg dry mass) and increased further by 120 min. Estimated free AMP increased (P < 0.05) from rest to 60 min and was approximately 20-fold greater than that at rest by 120 min. Epinephrine was increased above rest (P < 0.05) at 60 (1.47 +/- 0.15 nM) and 120 min (4.87 +/- 0.76 nM) of exercise. Insulin concentrations decreased rapidly and were lower than resting levels by 10 min and continued to decrease throughout exercise. In summary, HSL activity was increased from resting levels by 10 min, increased further by 60 min, and decreased to near-resting values by 120 min. The increased HSL activity at 60 min was associated with the stimulating effect of increased epinephrine and decreased insulin levels. After 120 min, the decreased HSL activity was associated with the proposed inhibitory effects of increased free AMP. The accumulation of LCFA CoA in the 2nd h of exercise may also have reduced the flux through HSL and accounted for the reduction in IMTG utilization previously observed late in prolonged exercise.     

Reduced plasma lipoprotein lipase activity in patients with malignancy-associated weight loss

Post-heparin plasma lipoprotein lipase activity was measured in 28 cancer patients with varying degrees of weight loss, and in 16 normal volunteers. Total lipoprotein lipase activity was decreased by 35.4% (P less than 0.001) in the cancer group. The component lipase activities, hepatic (HLPL), and peripheral (PLPL), were decreased by 40% (P less than 0.001) and 38% (P less than 0.005) respectively. In addition, the level of total peripheral lipoprotein lipase correlated well with the percent body weight lost by these patients (r = 0.6, P less than 0.01). Regardless of extent of disease, patients with lung cancer showed the lowest enzyme activity (mean 191 mU/ml +/- 30 SEM, P less than 0.001) and the greatest percent of weight loss (mean 16%), while patients with breast cancer had nearly normal lipase activity (mean 315 mU/ml +/- 50 SEM, normal 340 mU/ml +/- 22 SEM, P less than 0.10) and minimal weight loss (mean 8.4%). Fasting serum triglycerides were significantly elevated in the patient group (mean 120 mg/dl +/- 9.7 SEM) as compared to normal (mean 71 mg/dl +/- 7 SEM, P less than 0.001). The mean fasting insulin level was elevated in the patient group (13 mU/ml +/- 3.0 SEM), although in the majority of the patients it was found within the normal range (4-24 mU/ml). We conclude that the significant decrease in the total LPL activity may be responsible in part for the characteristic hypertriglyceridemia present in cancer patients.     

Regulation of lipoprotein lipase in muscle and adipose tissue during exercise.

Lipoprotein lipase (LPL) is regulated in a tissue-specific manner; exercise increases LPL activity in muscle at the same time it is reduced in adipose tissue. The purpose of this study was to determine the relationship between LPL activity and LPL mRNA in muscle and adipose tissue in rats exposed to one bout of exercise. Immediately after a 2-h swim, LPL activity [pmol free fatty acids (FFA).min-1.mg tissue-1] in the exercised animals was reduced 43% in adipose tissue (110 +/- 26 to 63 +/- 17) and increased almost twofold in the soleus muscle (203 +/- 26 to 383 +/- 59) compared with sedentary control animals. At the same time, LPL mRNA was reduced 42% in adipose tissue and increased 50 and 100% in the red vastus and white vastus muscles, respectively. Twenty-four hours after the swim, LPL activity had returned to control levels in adipose tissue and the soleus muscle. At hour 24 of recovery, LPL mRNA was still reduced 23% in the adipose tissue of exercised animals but was not significantly different between exercised and control animals in any of the muscle tissues analyzed. Changes in total RNA concentration could not account for the changes in relative LPL mRNA expression. The relationship between LPL enzyme activity and LPL mRNA in muscle and adipose tissue was +0.86 and +0.93 at 0 and 24 h postexercise, respectively. Thus the tissue-specific changes in enzyme activity induced by exercise could be mediated, in part, through pretranslational control.     

Exercise training has a heparin-like effect on lipoprotein lipase activity in muscle.

Lipoprotein lipase (LPL) is anchored with high affinity to heparan sulphate proteoglycans on the luminal surface of the capillary endothelium. The levels of pre-heparin perfusate LPL activity increased from 16 +/- 1 to 145 +/- 6 U/hindlimb (nine-fold increase) in hindlimb muscle of exercise-trained rats measured immediately after the last bout of work. At the same time, post-heparin perfusate LPL activity decreased from 63 +/- 2 to 13 +/- 1 U/hindlimb (p less than 0.001). These results provide evidence that exercise-training has a heparin-like effect on capillary-bound LPL. The total amount of LPL (i.e., pre-heparin perfusate plus post-heparin perfusate) was twofold greater in the hindlimb of the trained animals versus the controls. The effect of exercise on muscle LPL activity appears to last for as long as 5 days after cessation of exercise. Serum triglycerides were reduced 38% and plasma free fatty acids increased fourfold. These results provide evidence that training increases the capacity to remove triglycerides from circulation.     

The lipoprotein lipase (clearing-factor lipase) activity of cells isolated from rat cardiac muscle.

The total lipoprotein lipase activity recovered in suspension of cells prepared from adult rat hearts was unaffected by the nutritional state of the animals used. The enzyme activity present in the cell suspensions was almost exclusively associated with the cardiac muscle cells present as the major cell type.     

The significance of lipoprotein lipase in rat skeletal muscles.

Lipoprotein lipase was assayed in extracts of acetone-ether powders of rat skeletal muscles. Enzyme activity in soleus had typical characteristics of lipoprotein lipase in other tissues: inhibition by molar NaCl and protamine sulfate and activation by the human apolipoprotein, R-glutamic acid. Activity in muscles with predominantly red fibers (soleus, diaphragm, lateral head of gastrocnemius and anterior band of semitendinosus) was higher than in those with predominantly white fibers (body of gastrocnemius and posterior band of semitendinosus). No effect of a 24 hour fast upon enzyme activity was observed in ten skeletal muscles, but activity decreased substantially in four adipose tissue depots and increased slightly in heart muscle with fasting. Four minutes after intravenous injection of labeled lymph chylomicrons, skeletal muscles with predominantly red fibers incorporated several times more chylomicron triglyceride fatty acids than thos with predominantly white fibers. Estimated lipoprotein lipase activity in total skeletal muscle was about two-thirds that in total adipose tissue of rats fed ad libitum. After a 24 hour fast, total activity in skeletal muscle was about twice that in adipose tissue. These data suggest that a substantial fraction of lipoprotein lipase is in skeletal muscle of rats and that this tissue, especially its red fibers, is an important site of removal of triglycerides from the blood.     

Regenerative potential of human skeletal muscle during aging

In this study, we have investigated the consequences of aging on the regenerative capacity of human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate the in vivo turn-over and (ii) the proportion of satellite cells calculated as compared to the total number of nuclei in a muscle fibre. Two skeletal muscles which have different types of innervation were analysed: the biceps brachii, a limb muscle, and the masseter, a masticatory muscle. The biopsies were obtained from two groups: young adults (23 +/- 1.15 years old) and aged adults (74 +/- 4.25 years old). Our results showed that during adult life, minimum telomere lengths and mean telomere lengths remained stable in the two muscles. The mean number of myonuclei per fibre was lower in the biceps brachii than in the masseter but no significant change was observed in either muscle with increasing age. However, the number of satellite cells, expressed as a proportion of myonuclei, decreased with age in both muscles. Therefore, normal aging of skeletal muscle in vivo is reflected by the number of satellite cells available for regeneration, but not by the mean number of myonuclei per fibre or by telomere lengths. We conclude that a decrease in regenerative capacity with age may be partially explained by a reduced availability of satellite cells.     

Effect of capsaicin on skeletal muscle lipoprotein lipase in rats fed high fat diet

A synthetic analogue of capsaicin (0.2 mg%) fed to female Wistar rats along with a high fat diet for 11 weeks, lowered adipose tissue weight and also liver and serum triglycerides. The compound elevated total post heparin plasma lipase and skeletal muscle lipase activities. The increase in the latter indicates the possible mechanism by which capsaicin enhances serum triglyceride uptake by muscle tissue and in turn lowers triglyceride levels. A single dose of capsaicin even at a much higher level failed to lower serum triglycerides emphasizing the necessity of continuous ingestion of capsaicin for exerting its hypolipidemic effect.     

Epinephrine-activation of heparin-nonreleasable lipoprotein lipase in 3 skeletal muscle fiber types of the rat

Epinephrine was used to activate the heparin non-releasable lipoprotein lipase (LPL) in the 3 skeletal muscle fiber types of the perfused rat hindlimb. Following a 9 min washout of the capillary-bound lipoprotein lipase, the hindquarter of the rat was perfused with a buffer containing 10 nM of epinephrine. Activity of the residual LPL in soleus, red vastus lateralis, and white vastus lateralis muscles increased 75%, 96%, and 102% respectively, following epinephrine perfusion. These results suggest that skeletal muscle LPL is under hormonal control possibly through protein phosphorylation by cyclic AMP dependent protein kinase.     

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 +/- 2.4, GLU, 35.3 +/- 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 +/- 2.5, GLU, 2.1 +/- 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed (P < 0.05) HSLa relative to CON (120 min: CON, 1.71 +/- 0.18, GLU, 1.27 +/- 0.16 mmol.min-1.kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 +/- 0.06, GLU, 0.82 +/- 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 +/- 0.59, GLU, 1.37 +/- 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.     

Effects of reduced free fatty acid availability on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise.

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerol (IMTG); however, its regulation in skeletal muscle is poorly understood. To examine the effects of reduced free fatty acid (FFA) availability on HSL activity in skeletal muscle during aerobic exercise, 11 trained men exercised at 55% maximal O2 uptake for 40 min after the ingestion of nicotinic acid (NA) or nothing (control). Muscle biopsies were taken at rest and 5, 20, and 40 min of exercise. Plasma FFA were suppressed (P < 0.05) in NA during exercise ( approximately 0.40 +/- 0.04 vs. approximately 0.07 +/- 0.01 mM). The respiratory exchange ratio (RER) was increased throughout exercise (0.020 + 0.008) after NA ingestion. However, the provision of energy from fat oxidation only decreased from 33% of the total in the control trial to 26% in the NA trial, suggesting increased IMTG oxidation in the NA trial. Mean HSL activity was 2.25 + 0.15 mmol x kg dry mass(-1) x min(-1) at rest and increased (P < 0.05) to 2.94 +/- 0.20 mmol x kg dry mass(-1) x min(-1) at 5 min in control. Contrary to the hypothesis, mean HSL was not activated to a greater extent in the NA trial during exercise (2.20 + 0.28 at rest to 2.88 + 0.21 mmol x kg dry mass(-1) x min(-1) at 5 min). No further HSL increases were observed at 20 or 40 min in both trials. There was variability in the response to NA ingestion, as some subjects experienced a large increase in RER and decrease in fat oxidation, whereas other subjects experienced no shift in RER and maintained fat oxidation despite the reduced FFA availability in the NA trial. However, even in these subjects, HSL activity was not further increased during the NA trial. In conclusion, reduced plasma FFA availability accompanied by increased epinephrine concentration did not further activate HSL beyond exercise alone.     

CL-proteins and the regulation of lipoprotein lipase activity in locust flight muscle

Lipoprotein lipases in the flight muscles of Locusta migratoria show a marked substrate specificity: diacylglycerols associated with the adipokinetic hormone (AKH)-induced lipoprotein, A+, are hydrolysed at 4 to 5 times the rate of those associated with the lipoprotein in resting (non-hormone-stimulated) locusts, Ayellow. To determine the basis for this discrimination, the effect on the activity of flight muscle lipoprotein lipase of CL-proteins, a major constituent of lipoprotein A+, but not of Ayellow, has been investigated; they inhibit the flight muscle enzyme in a competitive manner whether activity is measured with a natural lipoprotein substrate, a lipid emulsion or a water soluble substrate. Experiments in vivo suggest that the flight muscle enzyme is normally inhibited in resting (non-AKH-stimulated) locusts but, interestingly, injection of synthetic AKH-I relieves the inhibition and increases the activity by 30 to 40%. This is not a direct effect of the hormone on the enzyme, but appears to be related to the hormone-induced formation of lipoprotein A+, so that the majority of CL-proteins in the haemolymph become bound to this lipoprotein and the concentration of free CL-proteins is markedly reduced. We suggest that CL-proteins play a major role in the regulation of lipoprotein lipase in locust flight muscle.