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W C Miller

Publications and source records attributed to W C Miller.

At least 91 records · Page 5Linked to original sources
PubMed1989

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.

Animals↗
PubMed1988

Effect of colchicine on alkaline triglyceride lipase activity and triglyceride content in rat skeletal muscle.

One purpose of this study was to determine if colchicine increased intracellular alkaline triglyceride (TG) lipase activity above control levels in rat skeletal muscle. The second aim was to determine the effects of colchicine treatment on the concentration of TG in skeletal muscle. The results show that colchicine was a potent inducer of alkaline TG lipase activity, increasing enzyme activity approximately twofold in slow-twitch red, fast-twitch red, and fast-twitch white muscle types. It was found that in slow-twitch red soleus and fast-twitch red vastus, the two muscle groups with the highest levels of enzyme activity, 76% or more of enzyme activity resides in the intracellular compartment. These results provide evidence that colchicine blocks the export of alkaline TG lipase from skeletal muscle cells similar to that seen in the heart. The finding that TG were reduced at a time when enzyme activity was elevated suggests that intracellular alkaline TG lipase may be playing a role in the hydrolysis of the intramuscular TG droplet.

Animals↗
PubMed1988

Effect of fasting on myocardial substrates in male and female rats.

Adult male and female rats were fasted for 1, 2, or 3 days to determine its effect on circulating and endogenous fuels available to the heart. Liver glycogen was depleted within the first 24 h of food restriction. Plasma glucose decreased approximately 2.5 mM in both sexes during the 3 days. Fasting significantly increased plasma beta-hydroxybutyrate to approximately the same level in female and male rats. Plasma free fatty acid (FFA) increased approximately 0.2 mM in both groups during the first 24 h without food and remained elevated over the next 2 days. FFA concentrations were higher in fed female than in fed male rats and remained significantly higher in female rats throughout the experimental period. Myocardial glycogen increased 64% during the first 2 days of fasting in the male rats and stayed elevated on the third day of fasting. In contrast, heart glycogen of female rats remained unchanged from an initial value of 3.13 mg/g throughout the 3-day fasting period. Endogenous triglyceride (TG) of male rats decreased from 2.14 +/- 0.09 to 1.41 +/- 0.21 mumol/g during the first 24 h without food and remained at that level during the second and third days. Heart TG in female rats fell progressively from 2.36 +/- 0.19 to 1.02 +/- 0.12 mumol/g during the fasting period. Cardiac FFA were higher in female than in male animals throughout the entire experiment. These data indicate that quantitative and qualitative metabolic differences exist between male and female rats stressed by fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Fatty acid binding proteins in the three types of rat skeletal muscle.

By means of Sephadex G-50 column chromatography, a Mr 12,000 fatty acid binding protein (FABP) was found to be present in all three types of skeletal muscle. FABP concentrations in muscle cytosols (105,000g supernatant) were fiber type specific with binding levels (expressed as pmole [14C]oleate bound/mg protein) of 70 +/- 7 in fast-twitch white (FTW) (heart FABP = 469 +/- 33). Cytosols from all three fiber types cross-reacted with antibody to pure heart FABP on Ouchterlony immunodiffusion analysis. FABP content, determined by radial immunodiffusion, followed the same pattern in the muscle types as that in the binding assay. The values (in micrograms/mg protein) were 3.3 +/- 0.1 in FTW, 17.0 +/- 0.4 in FTR, and 31.7 +/- 1.4 in STR fibers (heart = 55). Disc gel electrophoresis revealed a protein band in each fiber type that had migration identical to that of pure heart FABP and was proportional to the amounts determined by Sephadex G-50 chromatography and immunoassay. In addition, Western blots of tissue cytosols, using antibody to heart FABP, detected single protein bands identical in size to pure heart FABP in all three types of skeletal muscle. These results show the presence of a FABP in all skeletal muscle types with an immunologic and electrophoretic characterization identical to that of heart FABP.

Animals↗
PubMed1988

Role of the alkaline TG lipase in regulating intramuscular TG content.

Three TG lipases have been identified in muscle (i.e., acid, neutral, and alkaline), but as yet we do not know which enzyme is responsible for tissue TG hydrolysis. Over the past 8 yr, work in our laboratory has focused on intracellular lipoprotein lipase (LPL). The results show that this lipase is regulated by the classical cAMP cascade and that the activity of this enzyme is inversely related to endogenous TG concentration. Using these results as a foundation we plan to examine molecular mechanisms involved in the synthesis, compartmentalization, and transport of the alkaline TG lipase. Further, the evidence suggests that this enzyme may be regulated by protein phosphorylation mediated by cyclic AMP-dependent protein kinase. We plan to test this possibility.

Animals↗
PubMed1987

Effect of cholera toxin on triacylglycerol lipase activity and triacylglycerol content of rat heart.

This study was performed to reexamine the effect of cholera toxin on total and intracellular alkaline lipoprotein lipase (LPL) activity in rat heart. In addition, the relationship between intracellular triacylglycerol (TG)lipase activity and TG content of cardiac tissue was determined in cholera toxin treated rats. One intravenous injection of cholera toxin increased total LPL activity significantly above control activity 4 h following treatment. After 16 h, total enzyme activity in hearts of cholera toxin treated rats was 2.4-fold above control levels and remained significantly above the control activity up to the 24-h time point. Intracellular alkaline TG lipase activity was increased 24%, 59%, 2.1-fold, and 2.1-fold above control levels measured 0.5, 8, 16, and 24 h following cholera toxin treatment, respectively. Heart TG content fell significantly following cholera toxin treatment, with a maximal reduction seen 8 h following agent injection. At that time, TG was 0.61 mumol/g, a reduction of 63% below the control concentration of 1.8 mumol/g. A negative relationship between myocardial intracellular TG lipase activity and TG concentration of r = -0.83 was highly significant (P less than 0.001). These findings indicate that cholera toxin injection can increase total cardiac LPL activity and show that 70% of this increased activity is in the intracellular fraction. The highly significant relationship between enzyme activity and TG content support our working hypothesis that the intracellular TG lipase (LPL) is playing a role in regulating cardiac TG content.

Animals↗
PubMed1987

Characterization of the triacylglycerol lipase activity in three types of rat skeletal muscle.

The purpose of this study was to characterize the lipolytic activity of the alkaline triglyceride lipase in homogenates of three types of skeletal muscle obtained from heparin-perfused rat hindlimb. Specifically, the red portion of the vastus lateralis, the white portion of the vastus lateralis, and the soleus muscles were examined. To remove capillary-bound lipoprotein lipase from the capillary beds, muscle was perfused with an erythrocyte-free buffer containing 4% albumin, 5 units of heparin/mL, and 7.5 microM adenosine. Adenosine reduced perfusion pressure from 117 +/- 5 to 86 +/- 6 mmHg (1 mmHg = 133.32 Pa), providing evidence for an effective vasodilation. This vasodilation increased the amount of lipoprotein lipase removed from the capillary beds. By the end of the experiment, perfusates were lipoprotein lipase-free. Oxygen supply to the perfused hindlimb appeared adequate as evidenced by similar high energy phosphate values for perfused and contralateral control tissues. For example, in soleus muscle, ATP content was 4.5 +/- 0.6 vs. 4.2 +/- 0.3 mumol/g, ADP concentration was 1.0 +/- 0.2 vs. 1.4 +/- 0.2 mumol/g, and creatine phosphate level was 12.9 +/- 0.7 vs. 11.0 +/- 0.6 mumol/g for perfused and contralateral control soleus, respectively. In addition, K+ output by the hindlimb was negligible, while glycolytic flux of perfused muscle was similar to that measured in control tissue. The findings that triglyceride levels of soleus and red vastus lateralis were decreased suggest that endogenous triglyceride was providing energy for the hindlimb during perfusion. Skeletal muscle triglyceride lipase activity was stimulated by serum and heparin, inhibited by NaCl and protamine, and had a pH optimum of 8.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1987

Effects of dietary sugar and of dietary fat on food intake and body fat content in rats.

The long term ingestion of a sugar-rich diet (low fat) caused severe obesity in adult rats. In a separate experiment, the habitual consumption of a fat-rich diet (40% kcal from fat) also caused severe obesity. Severe obesity developed in both groups of animals even though they did not overeat. Voluntary food intake for the sugar-fed rats averaged 28,314 +/- 756 calories/rat per 55 wks which was similar to the value of 28,884 +/- 953 calories/rat per 55 wks for the fat-fed rats. However, both values were lower than that of 32,869 +/- 588 for the control rats eating Purina chow. Despite a lower caloric intake, carcass fat averaged 45 +/- 1% for rats eating the sugar-rich diet and 46 +/- 2% for rats eating the fat-rich diet, but only 33 +/- 2% for rats eating a diet of Purina chow. These results provide evidence that severe obesity can develop in the absence of hyperphagia in animals eating a sugar-rich or fat-rich diet. Finally, a rat model for severe obesity is presented in which carcass fat ranged from 18% (lean) to 61% (severe obesity) using dietary intervention alone at critical stages of the animal's life.

Adipose Tissue↗
PubMed1986

Anatomical lung shunting in pulmonary fibrosis.

Eleven patients with cryptogenic fibrosing alveolitis were evaluated for the presence of pulmonary shunting by injection of radiolabelled particles of macroaggregated albumin larger than 10 micron in diameter and by body scanning with a gamma camera. The mean shunt of 9% (SD 2%) in the patients was not significantly different from the mean shunt of 7% (2%) measured in 10 normal controls. These findings suggest that shunting is not an important part of the gas exchange abnormalities noted in such patients.

Humans↗
PubMed1986

Response of enlarged alveolar vessels to acute hypoxia.

Because the postulated mechanism of high altitude pulmonary edema is inhomogeneous vaconstriction and hyperperfusion of unconstricted vessels, pulmonary blood flow through vessels larger than 10 micron was determined at baseline and during acute hypoxia sufficient to reduce arterial oxygen saturation to 65%. Women demonstrated a uniform response of decreasing such flow, whereas responses in men were highly variable. Hyperperfusion of enlarged vessels during hypoxia is not an acute phenomenon in the majority of subjects and is therefore either unique to some individuals or a sub-acute occurrence.

Acute Disease↗
PubMed1986

Dietary-induced severe obesity: exercise implications.

A rat model for severe obesity has been developed by feeding the animals a fat-rich, sugar-rich diet. The concentration of fat in the diet was similar to what most Americans consume (about 40% kcal from fat). Calories from sugar was calculated to be 40.6%. As adults, body fat content in these animals averaged 61 or 51%, depending on whether the fat-rich, sugar-rich diet caused hyperphagia. The rate of body fat accretion in these severely obese rats raised in litters of four was estimated to be 1.78 +/- 0.12 (SE) g X d-1 (61% body fat) or 0.9 +/- 0.03 g X d-1 (51% body fat). In contrast, lean rats eating a diet of Purina chow deposited fat at a rate of 0.20 +/- 0.02 g X d-1, resulting in a carcass fat content of 18%. Preliminary evidence based on adult body weights of sugar-fed rats suggests that sucrose alone can cause severe obesity similar to that seen with dietary fat alone. Currently, an attempt is being made to determine how dietary fat and/or dietary sugar work to produce severe obesity. One possibility is that dietary fat in the form of a chylomicron and dietary sugar in the form of a very low density lipoprotein may modify adipose tissue lipoprotein lipase activity. This enzyme acts as a gatekeeper for circulating triglycerides entering the adipocyte. It is our belief that the results obtained will help to lay the groundwork for determination of the role of exercise in weight control.

Adipose Tissue↗
PubMed1984

Relationship between type L hormone-sensitive lipase activity and endogenous triacylglycerol in the hearts of colchicine-treated rats.

Colchicine injection was used as a tool to potentiate the increase in intracellular lipoprotein lipase (type L hormone-sensitive lipase) activity normally seen with fasting to determine if elevation of enzyme activity by this method produced a reduction in endogenous triacylglycerol (TG) in rat heart. Both fasting and fasting+colchicine treatment increased total lipoprotein lipase (LPL) activity from a control value of 80 units/g to approx. 144 units/g. The initial control value was obtained at 08:00 h after overnight feeding and the final values were obtained at 17:00 h, after 9 h of fasting. Fasting alone increased activity in both the capillary-bound LPL and type L hormone-sensitive lipase (HSL) fractions of cardiac muscle. In contrast, colchicine treatment, by blocking the export of enzyme from the cell as a result of microtubular disruption, restricted the increase in enzyme activity to the intracellular fraction of the heart. There was a highly significant (P less than 0.001) negative relationship (r = -0.73) between type L HSL activity and TG content in hearts of fasting and fasting+colchicine-treated rats. At a time when type L HSL activity was increased and TG content decreased, the cyclic AMP concentration of heart remained unchanged, ruling out the possibility that cyclic AMP might be activating any one of the identified cardiac TG lipases. These data provided indirect evidence that type L HSL is 'seeing the intracellular TG droplet' and that this enzyme may play a role in the regulation of myocardial lipolysis.

Animals↗
PubMed1984

High affinity binding sites for [3H]-nitrendipine in rabbit uterine smooth muscle.

The binding properties of the high affinity binding site for [3H]-nitrendipine on rabbit uteri membranes were investigated. The specific component had a dissociation constant of 0.46 +/- .07 nM and a maximal binding of 175 +/- 11 pmol/mg. A variety of other calcium channel blockers inhibited the binding of [3H]nitrendipine with varying potencies. Flunarizine demonstrated a high potency (IC50 = 0.30 microM) in inhibiting binding while verapamil and bepridil were less potent with IC50's of approximately 0.6-1.5 microM. Diltiazem did not displace nitrendipine even at very high concentrations. Verapamil displayed negative cooperative inhibition suggesting that a second site exists on uterine membranes for the binding of other calcium channel blockers.

Animals↗
PubMed1984

Relationship between type L hormone-sensitive lipase and endogenous triacylglycerol in rat heart.

The purpose of this study was to determine whether, under physiological conditions, intracellular lipoprotein lipase [type L hormone-sensitive lipase (HSL)] activity varied inversely with triacylglycerol (TG) content of the heart. The results show that fasting from 7:30 A.M. to 7:30 P.M. increased type L HSL activity from 72 +/- 1 to 96 +/- 1 U/g wet wt tissue (P less than 0.001) in the myocardium. At the same time, cardiac TG stores decreased from 1.83 +/- 0.03 to 1.37 +/- 0.01 mumol/g tissue (P less than 0.001). In a separate experiment, one night of eating a fat-rich diet (60% of calories from fat) caused a 42% increase in type L HSL activity, which was accompanied by a 42% reduction in the TG content of the heart. Likewise cold exposure (overnight) activated type L HSL (73%) and, at the same time, decreased cardiac TG stores (44%). When data from the fasting, fat-feeding, and cold-exposure experiments were combined, a significant correlation coefficient of -0.81 was obtained between type L HSL activity and TG content of the heart (P less than 0.001). These data provide evidence for a physiological relationship between intracellular lipoprotein lipase activity and cardiac TG content.

Animals↗