Biomedical subjects

A Angel

Publications and source records attributed to A Angel.

At least 19 recordsLinked to original sources

PubMed1992

Obesity and its relation to cardiovascular disease risk factors in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe the distribution of weight and abdominal obesity among Canadian adults and to determine the association of obesity with other risk factors for cardiovascular disease. DESIGN: Population-based cross-sectional surveys. Survey nurses administered a standard questionnaire and recorded two blood pressure measurements during a home visit. At a subsequent visit to a survey clinic two further blood pressure readings were made, anthropometric measurements recorded and a blood specimen taken for plasma lipid determination. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registration files of each province. Anthropometry was performed on 17,858 subjects. OUTCOME MEASURES: Body mass index (BMI), ratio of waist to hip circumference (WHR), mean plasma lipid levels, prevalence of high blood pressure (diastolic greater than or equal to 90 mm Hg or patient on treatment) and self-reported diabetes mellitus. MAIN RESULTS: The prevalence of obesity (BMI greater than or equal to 27) increased with age and was greater in men (35%) than in women (27%). Abdominal obesity was likewise higher in men and increased with both age and BMI. The prevalence of high blood pressure was greater in those with higher BMI, especially in those with a high WHR. Although total plasma cholesterol levels increased only modestly with BMI, levels of low density lipoprotein (LDL) cholesterol and triglycerides and the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol increased steadily, while HDL-cholesterol decreased consistently with increasing BMI. High total cholesterol levels (greater than or equal to 5.2 mmol/L) were more prevalent among people with high BMI, especially those with a high WHR. The prevalence of diabetes increased with BMI among those 35 years or older, especially those with abdominal obesity. About half of men and two-thirds of women who were obese were trying to lose weight. CONCLUSION: Obesity remains common among Canadian adults. There is a need for broad-based programs that facilitate healthy eating and activity patterns for all age groups. Health professionals should incorporate measurement of BMI and WHR into their routine examinations of patients to enhance their evaluation of health risk.

Adult↗

PubMed1992

A comparison of the effects of propofol with other anaesthetic agents on the centripetal transmission of sensory information.

1. A range of anaesthetic agents affect the centripetal transmission of sensory transmission by activating cortico-thalamic inhibitory mechanisms. 2. This transmission of information through thalamic sensory relay nuclei is impeded and the sensory flow to the cerebral cortex is considerably reduced. 3. In addition cortical transfer of information is blocked since cells in layers III and V show an additional sensitivity to anaesthetic agents. 4. Diprivan (2,6-diisopropylphenol, propofol, ICI) appears to exert an action on sensory transmission mainly by acting on cortical cells in layers III and V. 5. Its action on thalamic sensory relay cells is to increase their latency of discharge and disrupt their pattern of firing.

Anesthetics↗

PubMed1991

Dietary fish oils modify adipocyte structure and function.

Dietary fish oils, enriched with omega-3 fatty acids (e.g., MaxEPA fish oil), inhibit lipogenesis and have a marked hypotriglyceridemic effect in man and experimental animals. Dietary omega-3 fatty acids also reduce adipose tissue trophic growth in rats. To understand the metabolic basis for this, we measured the effect of fish oil feeding upon rat plasma triglyceride concentration, fat pad mass, fat cell size, fat cell lipolysis, as well as lipoprotein binding to adipocyte plasma membranes. In adolescent (250 g) male Wistar rats fed 20% (w/w) fish oil supplemented diets for 3 weeks, plasma triglyceride levels and epididymal and perirenal fat pad mass were significantly (P less than 0.005) reduced compared to pair-fed controls given 20% lard diets. These differences in fat pad mass between the diets were greater than differences in whole animal mass or in the mass of livers, testes, kidneys, spleens, or hearts. Isoproterenol-stimulated lipolysis was significantly (P less than 0.005) higher in fish oil fed rats than in pair-fed controls. In young (100 g) rats plasma triglyceride levels were 10 times lower in the fish oil fed group after 5 weeks as compared to the lard-fed controls. This was accompanied by a reduction in epididymal and perirenal fat pad mass as well as a 2-3-fold decrease in adipocyte volumes; there was no significant difference between the two groups in fat cell number in each region. Plasma membranes of epididymal adipocytes from fish oil fed rats bound significantly (P less than 0.001) less HDL1 than the lard-fed rats, possibly as a result of a reduction in fat cell size and/or alteration of plasma membrane structure. Thus in both young and old rats, the reduction in plasma triglyceride concentration in conjunction with increased hormone-stimulated lipolysis may explain in part the selective reduction in adipose tissue trophic growth accompanying fish oil consumption.

Adipose Tissue↗

PubMed1991

Biogenic amine localization in cardiac ganglion intrinsic neurons: electron microscopic histochemistry of SIF cells.

The parasympathetic cardiac ganglion in the mudpuppy, N. maculosus, contains postganglionic nerve cells and intrinsic neurons, many of which are small intensely fluorescent (SIF) cells. Several bioactive substances have been localized in the intrinsic nerve cells which may have integrative effects at synapses within the ganglion. Ganglionic intrinsic neurons can be identified electron microscopically by the presence of numerous cytoplasmic granular vesicles 80-120 nm in diameter. Throughout the ganglion there are bundles of unmyelinated fibers some of which are filled with granular and agranular vesicles and axosomatic terminals with similar vesicles synapsing on principal parasympathetic nerve cells. To understand the aminergic contribution to ganglionic synaptic circuitry the chromaffin reaction was used. The intrinsic neurons (i.e., SIF cells) were readily identified by their characteristic intracellular granule population. All intrinsic nerve cells identified showed granules which were positively labelled by the chromaffin reaction. Granular vesicles in synaptic profiles on principal cells (P cells) were also labelled indicating a direct aminergic synaptic innervation to these cells. The cell bodies of intrinsic neurons, ensheathed with supportive glial-like cellular processes, rarely received synapses. Elemental microanalysis was used to verify the chromium content of the electron dense product within the granular vesicles. These studies demonstrated direct aminergic synaptic input to at least a subpopulation of principal parasympathetic cells in the cardiac ganglion of mudpuppy.

Animals↗

PubMed1991

The G. L. Brown lecture. Adventures in anaesthesia.

The results presented in this lecture show that anaesthetic agents impede the transfer of information from the periphery to the cerebral cortex. This is shown both as a reduction in the amplitudes of the initial positive and negative waves of the cerebral cortical response evoked by simulation of the periphery and as an increase in the latency of this response. This effect is most probably a prime effect of anaesthesia since (a) it is common to all the anaesthetics used, (b) the potency of the anaesthetics is directly proportional to their lipid solubility, and (c) the effect is reversed by high ambient pressures. The major site at which information transfer is most susceptible to the action of anaesthetics is at the level of the ventrobasal thalamus, although the cells in cortical layer V also appear to have an enhanced susceptibility to anaesthetic action. This latter observation is seen both in whole animal and cortical slice preparations. None the less, the first site of synaptic transfer at which anaesthetics exert a profound effect is upon the monosynaptically generated responses of ventrobasal thalamic neurones to cuneothalamic input. A possible mechanism of action for anaesthetic agents acting at this site would be upon a hypothetical cortico-thalamic-reticular-thalamic loop with the theoretical ability to control the responsiveness of the ventrobasal thalamic cells. This action was proposed both from the activity of neurones in response to anaesthetic agents and the anatomical arrangement seen in the thalamus. The thalamic reticular nucleus is a curved sheath of cells situated between the internal capsule and the external medullary lamina, capping and bounding laterally the specific nuclei of the dorsal thalamus. There is both anatomical and physiological evidence that the thalamic reticular nucleus comprises part of the thalamic reticular formation: its cellular structure also resembles that of the brain stem regions of the reticular formation (Ramon-Moliner, 1975). Early degeneration and Golgi studies showed that ascending fibres from the medial parts of the pontine and mesencephalic components of the brain stem reticular formation innervated the thalamic reticular nucleus ventrally, by penetrating the zona incerta, and dorsally, via the intralaminar and dorsal thalamic nuclei (Scheibel & Scheibel, 1958). These observations have been confirmed and extended more recently and it appears that the major innervation of the thalamic reticular nucleus occurs via the ventral route which follows the entire course of the reticular nucleus. No fibres ascending from the dorsal column lemniscal system, the spino-cervico-lemniscal system or the spinothalamic tract have been observed to terminate within the thalamic reticular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗

PubMed1990

Spontaneous single cell discharge in rat somatosensory cortical slices and its relationship to discharge in the urethane-anaesthetized rat.

A slice preparation of rat somatosensory cortex has been used to observe the nature of spontaneous single cell discharge in layer V. On the basis of their discharge pattern, cells recorded using extracellular microelectrodes fell in to one of two categories: 70% of cells discharged single action potentials separated by relatively constant time intervals, while the remainder discharged in bursts of 2-7 action potentials. The firing patterns and the range of discharge frequencies observed were similar to those recorded in the same region and layer of the cortex in urethane-anaesthetized rats. However, unlike cells recorded in vivo, the majority of cells in slices never changed their discharge pattern. This suggests that while these layer V cells in cortical slices have the basic ability to discharge spontaneously, the potential for switching between discharge patterns requires circuitry absent from this isolated preparation. Urethane, over the dose range 6-24 mM, caused a dose-dependent decrease in the discharge frequency of cells with a regular firing pattern but did not affect their basic pattern of discharge.

Anesthesia, General↗

PubMed1990

Preparing and analyzing fractured archaeological fibers.

A technique was developed to prepare archaeological fiber cross sections for electron microscopic examination and x-ray analysis. Use of this new method allows chemical and morphological information to be obtained from the interior of a single fiber or yarn. Fibers are fractured while frozen and then freeze dried. Following mounting and carbon coating, fibers are examined by scanning and backscatter electron microscopy and then analyzed by using energy-dispersive spectrometry. Elemental distribution is mapped by using image-processing software. In this report, the described technique is employed in the examination of ancient fibers from three different long-term storage environments (moist buried, dry buried, museum stored). Data obtained by examining the interior of fibers such as these provide insight into the conditions of a fiber's growth, the treatments applied during the fiber's processing and use, and the conditions in which the fiber was stored.

Archaeology↗

PubMed1990

Dietary fish oils limit adipose tissue hypertrophy in rats.

Total body mass, fat pad mass, and fat cell size were examined after feeding rats diets containing 20% triglycerides from fish oil or lard. Although food consumption, weight gain, and fat balance on the two diets were similar, lard-fed rats had 77% more fat in perirenal fat pads and 51% more fat in epididymal fat pads compared with fish oil-fed rats. There was no difference between the two groups in fat cell number in each region; however, adipocytes were significantly smaller in fish oil-fed rats. Thus dietary fish oil appears to limit triglyceride accumulation in adipose tissue and thereby limit fat cell trophic growth.

Adipose Tissue↗

PubMed1990

Changes in dietary lipid saturation modify fatty acid composition and high-density-lipoprotein binding of adipocyte plasma membrane.

Binding of rat high-density lipoprotein (HDL) to adipocyte plasma membranes appears to be mediated by specific protein-recognition sites, but membrane lipids may also affect these interactions. To study the effect of dietary fatty acid composition on adipocyte-membrane phospholipid composition and HDL binding, male Wistar rats (250 +/- 10 g) were fed diets high in polyunsaturated (20% wt:wt sunflowerseed oil) or saturated and monounsaturated fatty acids (20% lard, by weight). Sunflower-oil vs lard feeding significantly increased the polyunsaturated fatty acid content of membrane diacylglycerophospholipids and the (22:0 and 24:0) content of long-chain fatty acids of sphingomyelin (p less than 0.05) from epididymal and perirenal adipocyte plasma membranes. Concomitant with these changes in membrane phospholipid composition, sunflower-oil vs lard treatment significantly increased the maximum binding capacity (Bmax) of 125I-labeled HDL2 (p less than 0.05). These results show that feeding polyunsaturated fatty acids enhanced HDL2 Bmax of adipocyte plasma membranes, possibly as a consequence of altering the fatty acid composition of membrane phospholipids.

Adipose Tissue↗

PubMed1990

Dietary polyunsaturated fatty acids enhance the uptake of high-density lipoprotein cholesterol ester by rat adipocytes.

Compared with diets high in saturated and monounsaturated fatty acids (20% lard by weight), diets high in polyunsaturated fatty acids (20% sunflower oil) alter the fatty acid composition of rat adipocyte plasma membranes and enhance HDL2 binding. We examined the effect of these two diets on HDL1 and HDL2 apolipoprotein and cholesterol uptake by adipocytes isolated from perirenal and epididymal adipose tissue of male Wistar rats. Consistent with selective cellular uptake. HDL esterified cholesterol uptake was 3-10-fold higher than predicted from HDL apolipoproteins associated with adipocytes. Dietary polyunsaturated fatty acids significantly enhanced apolipoprotein and esterified-cholesterol uptakes from HDL2 by perirenal adipocytes. This effect of dietary fat composition was adipose-region (perirenal greater than epididymal) and HDL-subfraction (HDL2 greater than HDL1) specific. Thus, diet-induced changes known to alter membrane phospholipid composition and increase HDL2 binding are also associated with enhanced HDL2-esterified-cholesterol uptake by adipocytes.

Adipose Tissue↗

PubMed1990

Alterations of "sleeping time" in the rat induced by drugs which modulate central monoaminergic systems.

The effects of adrenoceptor agonists and antagonists have been determined on "sleeping time" in the rat--that is, with the animal immobile and adopting a sleeping posture. Alterations in their gross behaviour patterns were assessed also. The specific alpha 2-adrenoceptor agonists (yohimbine, WY 26393, RX 781094 and RS 21361) decreased sleeping time, as did the beta-adrenoceptor agonist clenbuterol. The specific alpha 2-adrenoceptor agonist clonidine gave a large increase in sleeping time at doses in excess of 25 micrograms kg-1. The same effect was seen with the beta-antagonist propranolol and the specific beta 2-antagonist ICI 118551.

Adrenergic alpha-Agonists↗

PubMed1990

Selective uptake of cholesteryl ester from high density lipoproteins by plasma membranes of adipose tissue.

The interaction between high density lipoproteins (HDL) and adipose tissue is an important pathway for cholesterol and cholesteryl ester flux. In intact fat cells, a disproportionately greater net uptake of cholesteryl ester occurs subsequent to lipoprotein binding than would have been predicted from a consideration of holoparticle uptake alone. To characterize the early events in this process, cholesteryl hexadecyl ether, a nonmetabolizable, accumulative marker of cholesteryl ester, was incorporated into canine HDL2, and its uptake by omental adipocyte plasma membranes was measured in relation to the binding of HDL2, which in this animal species is enriched in apolipoprotein A-I and free of apolipoprotein E. The dose-response profile for HDL2 binding was consistent with a single lipoprotein binding site at all concentrations of HDL2, whereas uptake of cholesteryl ester from HDL2 was biphasic, suggesting a high affinity site at low HDL2 concentrations and a low affinity site at high lipoprotein concentrations. Pronase treatment stimulated binding twofold and this was accompanied by a parallel twofold stimulation of cholesteryl ester uptake. EDTA, on the other hand, reduced binding and uptake of cholesteryl ester by 20%, indicating partial dependence upon divalent cations. The proportion of HDL2 cholesteryl ester accumulated by plasma membranes relative to HDL2 protein bound was not altered by either pronase or EDTA, despite the fact that these agents had opposite effects upon binding. In dissociation studies, a portion of membrane-associated HDL2 did not equilibrate with exogenous HDL2 and a greater proportion of the cholesteryl ester failed to dissociate. A stepwise mechanism for cholesteryl ester uptake, involving (i) saturable, high affinity HDL2 binding to cell surface sites, (ii) vectoral, HDL2 concentration-dependent delivery of cholesteryl ester to the membrane, and (iii) cholesteryl ester sequestration into a nonexchangeable membrane compartment, appears to be independent of metabolic energy or cell processing.

Adipose Tissue↗

PubMed1990

Enhanced binding of phospholipase-A2-modified low density lipoprotein by human adipocytes.

Recognition of low density lipoprotein (LDL) by human adipocytes is not dependent on the classical LDL (apoprotein B-E) receptor. To assess whether LDL phospholipids have a role in adipocyte-LDL interactions, binding studies were carried out with human LDL modified with cobra venom phospholipase A2 (PLA2) and freshly isolated adipocytes and purified adipocyte plasma membranes prepared from surgical biopsies. LDL incubated with PLA2 showed increased monoacylphospholipid content, decreased diacylphospholipid content, and increased anodic migration on agarose gel electrophoresis. LDL cholesterol, triglyceride, and protein content remained unchanged. Typically, modification of 16 and 47% of LDL phospholipids enhanced specific binding of 125I-labelled LDL to plasma membranes progressively from 3.1 micrograms LDL bound/mg membrane protein (control) to 5.8 and 28.2 micrograms LDL bound/mg membrane protein, respectively. Nonspecific binding was not altered significantly. Excess unlabelled native LDL and high density lipoprotein (HDL3) effectively inhibited binding of PLA2-modified LDL. Freshly isolated adipocytes also showed enhanced binding and uptake of PLA2-modified LDL (0.1 vs. 0.9 micrograms LDL/10(6) cells x 2 h), control vs. modified). The results demonstrate that alterations of LDL phospholipids significantly enhance LDL binding and suggest a regulatory role for phospholipids in lipoprotein-cell interaction. Furthermore, the results support the view that human adipose tissue may be involved in the metabolism of modified lipoproteins, in vivo.

Adipose Tissue↗

PubMed1989

Proteolytic degradation of HDL1 on the fat cell surface is nutritionally regulated.

The importance of plasma HDL apolipoprotein concentration as a predictor of atherosclerotic risk is well recognized, yet the processes of HDL modification and degradation in various cells are not clearly understood. We examined the characteristics of HDL1 apolipoprotein degradation and cellular uptake by rat adipocytes and determined the effects of fasting on these processes. Epididymal and perirenal adipocytes were isolated from male Wistar rats (310 +/- 4 g) fed ad libidum and incubated with 5 micrograms of rat 125I-labeled HDL1 (d: 1.07-1.10 g/mL) mL-1 for 2 h at 37 degrees C. Cellular uptake of HDL1 was calculated as the trichloroacetic acid precipitable radioactivity associated with adipocytes following incubation. Intracellular and medium degradation of HDL1 were determined as trichloroacetic acid soluble 125I counts associated with cells and measured in the postincubation medium, respectively. Fifty to sixty percent of cellular uptake and degradation of HDL1 was inhibited by the addition of 25-fold excess unlabeled HDL. HDL1 degradation measured in the medium was 10- to 12-fold greater than cellular uptake of HDL1 apolipoproteins. Intracellular degradation of HDL1 was negligible. The presence of EDTA in the incubation medium reduced HDL1 degradation measured in the medium, but enhanced HDL1 cellular uptake. Conditioned medium separated from cells after 2 h of incubation at 37 degrees C in the absence of HDL and subsequently incubated with 125I-labeled HDL1 for an additional 2 h at 37 degrees C, degraded less than 5% of HDL compared with degradation in the presence of cells. These results suggest that rat adipocytes degrade, or modify, HDL1 particles, possibly by interactions with cell surface proteases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1989

Effect of massive obesity on low and high density lipoprotein binding to human adipocyte plasma membranes.

Adipose tissue is a major cholesterol storage organ in man, and turnover of this slowly exchangeable pool is dependent on low and high density lipoproteins which deliver and remove cholesterol from this site. To determine whether lipoprotein binding is altered in the obese state, we examined the binding of low density lipoprotein (LDL) and high density lipoprotein (HDL2 and HDL3) to purified adipocyte plasma membranes obtained from omental fat depots of massively obese patients (BMI greater than 40 kg/m2) and lean subjects. The specific binding and uptake of 125I-HDL2 and 125I-HDL3 were greater for obese than for lean adipocytes. Scatchard analysis of binding studies using purified adipocyte plasma membranes and varying amounts of labeled HDL2 or HDL3 demonstrated a higher binding affinity (lower Kd) for HDL2 and higher binding capacity (Bmax) value for both HDL2 and HDL3 in obese as compared to lean. 125I-LDL specific binding was somewhat lower in obese than in lean membranes but this difference was not statistically significant. The cholesterol content of isolated omental adipocytes expressed on a cellular basis or as the cholesterol/triglyceride ratio (mg chol/g of lipid) were similar in the obese and lean subjects. Furthermore, 125I-LDL, 125I-HDL2 or 125I-HDL3 specific binding did not correlate with cellular cholesterol content or with cholesterol/triglyceride ratio. These findings indicate that lipoprotein binding to adipocytes is altered in obesity and is characterized by up-regulation of HDL (particularly HDL2) binding with little change in LDL binding. We conclude from this study that obesity has a profound effect on the expression of HDL binding sites in human adipocytes and that LDL and HDL binding in fat cells are regulated differently.

Adipose Tissue↗

PubMed1979

Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients.

Biopsies of adipose tissue, liver and small bowel mucosa obtained from grossly obese and control subjects were used to study absolute rates of fatty acid, cholesterol, and other nonsaponifiable lipid synthesis using glucose as substrate and 3H2O as the isotopic marker. Fatty acid synthesis in subcutaneous adipose tissue expressed on a cell basis was greater in obese than control subjects and was stimulated by a high concentration of insulin (1000 micro U/ml), but not by a lower amount (100 micro U/ml). Fatty acid synthesis in omental adipose tissue exceeded by 3-fold that of subcutaneous fat. Fatty acid synthesis in obese liver was twice that of control liver and 20 times greater than obese adipose tissue. In terms of total organ activity fatty acid synthesis in fat tissue equalled or exceeded that of liver in both obese and control subjects. The cholesterol content of obese adipose tissue 1.86 +/- 0.11 mg/g exceeded that of controls 1.47 +/- 0.07 mg/g. All tissues examined synthesized cholesterol and nonsaponifiable lipids, liver greater than adipose tissue greater than small bowel mucosa. Nonsaponifiable lipid synthesis per gram of adipose tissue or liver was similar in obese and control tissue. The synthesis of total nonsaponifiable lipids including sterols, hydrocarbons and squalene was appreciable in adipose tissue and was approximately 15% of that of liver. However, cholesterol synthesis in the liver exporessed in terms of total organ activity was 50 times that in adipose tissue. The study demonstrates by direct comparison that liver is the dominant cholesterogenic organ in man and also shows that adipose tissue is a significant site of formation of fatty acids and nonsaponifiable lipids.

Adipose Tissue↗

PubMed1979

Low density lipoprotein binding, internalization, and degradation in human adipose cells.

Human adipose tissue derives its cholesterol primarily from circulating lipoproteins. To study fat cell-lipoprotein interactions, low density lipoprotein (LDL) uptake and metabolism were examined using isolated human adipocytes. The 125I-labelled LDL (d = 1.025-1.045) was bound and incorporated by human fat cells in a dose-dependent manner with an apparent Km of 6.9 + 0.9 microgram LDL protein/mL and a Vmax of 15-80 microgram LDL protein/mg lipid per 2 h. In time-course studies, LDL uptake was characterized by rapid initial binding followed by a linear accumulation for at least 4 h. The 125I-labelled LDL degradation products (trichloroacetic acid soluble iodopeptides) accumulated in the incubation medium in a progressive manner with time. Azide and F- inhibited LDL internalization and degradation, suggesting that these processes are energy dependent. Binding and cellular internalization of 125I-labelled LDL lacked lipoprotein class specificity in that excess (25-fold) unlabelled very low density lipoprotein (VLDL) (d less than 1.006) and high density lipoprotein (HDL) (d = 1.075-1.21) inhibited binding and internalization of 125I-labelled LDL. On an equivalent protein basis HDL was the most potent. The 125I-labelled LDL binding to an adipocyte plasma membrane preparation was a saturable process and almost completely abolished by a three- to four-fold greater concentration of HDL. The binding, internalization, and degradation of LDL by human adipocytes resembled that reported by other mesenchymal cells and could account for a significant proportion of in vivo LDL catabolism. It is further suggested that adipose tissue is an important site of LDL and HDL interactions.

Adipose Tissue↗

PubMed1979

Inhibition of rat and human adipocyte adenylate cyclase in the antilipolytic action of insulin, clofibrate, and nicotinic acid.

Clofibrate (Atromid-S), nicotinic acid, and insulin are known to be potent hypolipidemic and antilipolytic agents. The present study was undertaken to define the mechanism of action of this latter effect on isolated rat and human fat cells. Sodium clofibrate (0.42 mM), nicotinic acid (0.42 mM), and insulin (100 microU/mL) were shown to inhibit norepinephrine-stimulated lipolysis in rat and human adipose cells and this inhibition was associated with a reduction in intracellular 3',5'-cyclic AMP levels. A similar cyclic AMP lowering effect was demonstrated with insulin in the presence of procaine-HCL, which uncouples the adenylate cyclase system from lipolysis. This insulin effect was attributed to inhibition of adenylate cyclase. A direct and significant inhibition of adenylate cyclase in membrane fractions obtained from isolated human adipocytes was demonstrated for all three antilipolytic agents. The common membrane site of action of these agents whereby adenylate cyclase activity is depressed, thus decreasing cyclic AMP production and free fatty acid (FFA) mobilization from adipose stores, implies a central role for the adenylate cyclase system. These findings are consistent with the view that the hypotriglyceridemic effects of clofibrate, nicotinic acid, and insulin may be partly explained by deprivation of FFA substrate for hepatic very low density lipoprotein synthesis.

Adenylyl Cyclase Inhibitors↗