Search

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research. Background/Introduction Excessive epicardial adipose tissue (EAT) is associated with worse exercise capacity and is thought to play a role in the pathophysiology of heart failure with preserved ejection fraction. Few studies have explored the relationship between EAT, cardiorespiratory fitness in men and women without cardiovascular disease. Purpose To investigate the association between EAT, cardiorespiratory fitness, and physical activity levels in asymptomatic men and women of variable degree of adiposity. Methods A total of 239 participants (43% women) free from cardiovascular disease who underwent concurrent quantification of EAT volume assessed by cardiac magnetic resonance and a cardiopulmonary exercise testing (CPET) (VO2peak [ml/kg/min]) were studied. Physical activity levels/intensity were measured by questionnaire and using pedometer. Participants were categorized into low-EAT, moderate-EAT, and high-EAT groups on the basis of EAT volume. Results Mean age of participants was 49.8 ± 8.3 years, BMI 26.0 ± 3.7 kg/m2 (15% with obesity), waist circumference 89 ± 11 cm, visceral adipose tissue volume 91.3 ± 51.3 cm3, and EAT volume 9.8 ± 3.1 cm3. EAT volume decreased with increment in cardiorespiratory fitness in men and women of variable adiposity (p Conclusions In men and women of variable degree of adiposity, excessive EAT accumulation is associated with visceral adiposity and worse cardiorespiratory fitness. Further longitudinal studies are needed to understand the interplay between EAT and cardiorespiratory fitness, and the development of obesity-related heart failure features.

Background — Fasting levels of plasma lipids and lipoproteins are reported to improve with regular exercise training. However, little is known on whether the training responses are influenced by heritable factors. Methods and Results — The lipid profile was assessed in 115 black (224 individuals) and 99 white families (469 individuals), who participated in the HERITAGE Family Study, while in a sedentary state (baseline visit) and after exercise training for 20 weeks (post visit). Variables included total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I, and HDL-C subfractions 2 (HDL 2 -C) and 3 (HDL 3 -C). Familial correlations for the training responses (Δ=post−baseline) were significant for most variables, and the percent variance accounted for by familial factors (ie, maximal heritabilities) ranged from 25% to 38%. Exceptions were for higher heritabilities near 60% for ΔApoB in blacks and ΔHDL 2 -C in whites and a lower estimate of zero for ΔLDL-C in blacks. Conclusions — Heritable factors in part determine lipid profile responses to regular exercise. Maximal heritabilities were similar across ethnic groups and variables, except for ΔLDL-C, ΔApoB, and ΔHDL 2 -C. Molecular studies to identify the markers and genes associated with these influences are currently underway.

The effects of long-term (93 days) negative energy balance on plasma glucose and insulin were investigated by means of exercise with constant energy intake in seven pairs of young sedentary male identical twins. Results showed a significant decrease in fasting (-24%, P < 0.02) and postprandial insulin (-16%, P < 0.05). Fasting and postprandial plasma glucose and glucagon were not modified. Mean glucose disposal rate measured during a euglycemic-hyperinsulinemic clamp performed in five twin pairs was increased by 34% (P = 0.13). No significant intrapair similarity was found for the responses of fasting and postprandial insulin levels and of glucose disposal rate. Changes in glucose disposal rate were significantly greater in high compared with low losers for computerized tomography-measured abdominal visceral fat (3.0 +/- 1.1 vs. 0.3 +/- 0.5 mg x kg(-1) x min(-1), P < 0.05) despite similar losses in total body fat. We conclude that 1) a long-term negative energy balance generated by exercise training significantly reduces plasma insulin levels, whereas insulin sensitivity tends to be improved; 2) training-induced changes in insulin sensitivity are associated with changes in abdominal visceral fat; and 3) data from this experiment conducted with a small number of twin pairs suggest that the genotype does not seem to be a major determinant of the changes in insulin levels and sensitivity brought about by negative energy balance with exercise.

The clinical performance of the Medtronic Intact porcine bioprosthesis was evaluated in 1,084 patients (mean age 66.4 years, range 9 to 91 years) who had a total of 1,099 implantations between 1985 and 1992, inclusive. There were 709 aortic valve replacements, 297 mitral valve replacements, and 80 multiple valve replacements. Concomitant procedures were performed in 432 (39.3%). The age group distribution (years) was 35 or younger in 20 patients, 36 to 50 in 64, 51 to 64 in 274, 65 to 69 in 225, 70 or older in 500. The total follow-up time was 2,741 patient-years (mean, 2.5 years) and was 97.5% complete. The early mortality rate was 7.1% and late mortality was 3.9% per patient-year. The overall patient survival at 7 years was 70% ± 3%. The freedom from major thromboembolism was 94% ± 1% at 7 years ( p = not significant for valve positions). The freedom from reoperation at 7 years was 93% ± 1%; freedom from valve-related mortality was 89% ± 2%. The freedom from structural valve deterioration at 7 years was 97% ± 1% (aortic valve replacement 97% ± 1%; mitral valve replacement 97% ± 2%). The freedom from structural valve deterioration among age groups was not different for the overall population, aortic valve replacement, or mitral valve replacement. Hemodynamic assessment revealed obstructive properties for aortic valve replacement sizes of 21 and 23 mm and for mitral valve replacement sizes of 25 and 27 mm. The Medtronic Intact porcine bioprosthesis shows excellent freedom from structural failure at 7 years for all valve positions and age groups, but obstructive properties for small aortic and mitral valve sizes.

The authors' reply: Although the objective of my review paper2 was not to address the relevance of measuring waist circumference in children, I certainly agree with de Groot et al 1 …

With the advent of modern therapy, it has become essential to obtain a tissue diagnosis in all cases of pulmonary and mediastinal disease. Since it is often necessary to resort to thoracotomy as a final step in making such a diagnosis, we have sought a procedure that is simpler while capable of providing the same information. Through a standard cervical mediastinoscopy incision, the mediastinum is first explored; if the diagnosis is not obtained, the mediastinal pleura is digitally opened and lung or pleural biopsies are taken. In the course of 1,100 mediastinoscopies since 1969, 275 pleuroscopies have been done. We were able to obtain a tissue diagnosis in 102 (78%) of 131 patients with bronchogenic carcinoma, in 92 (91%) of 102 with benign pulmonary disease, and in all 20 (100%) with pleural disease.

To determine the effect of obesity on the size distribution of fat cell populations in human adipose tissue, omental fat tissue biopsies were obtained from lean, moderately obese, and massively obese patients. The size distributions of adipocytes from lean and obese fat tissues examined by the scanning electron microscopic method were bimodal, consisting of populations of very small fat cells and mature fat cells, in contrast to collagenase-derived isolated cells that showed only the large mature fat cells. The very small fat cell population represented 21 to 26% of the total fat cell number in the lean and in both obese groups. In contrast, preparations of human fat cells isolated by the collagenase method systematically excluded the very small fat cells. In massive obesity, both cell populations participated in the hyperplastic growth but only the larger mature fat cells increased in size, implying that these two cell populations differ in their physiological role.

Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. We have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37 degrees C with 10 micrograms/ml 125I-HDL2 or 125I-HDL3. In both depots, the cellular uptake of 125I-HDL2 and 125I-HDL3 was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of 125I-HDL2 and 125I-HDL3. In obese patients, the uptake of 125I-HDL was higher in subcutaneous cells than in omental cells [5.85 +/- 0.53 vs. 2.74 +/- 0.30 pmol X 2 h-1. (10(6) cells)-1]. The cellular 125I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio).(ABSTRACT TRUNCATED AT 250 WORDS)

Human obesity is frequently associated with elevated plasma triglyceride and cholesterol concentrations and reduced high density lipoprotein (HDL) cholesterol, abnormalities that commonly revert to normal levels with weight loss. This study was undertaken to examine possible mechanism(s) associated with the changes in plasma HDL cholesterol concentrations in massively obese patients after weight loss. Ten massively obese patients (two men and eight women, age = 37.8 ± 2.4 years) were studied before, during, and after 1 year of weight loss and weight maintenance following gastric stapling. Total cholesterol and low density lipoprotein cholesterol were within the normal range for sex and age before weight loss and did not change significantly during or after weight reduction. In the females, HDL cholesterol concentrations increased from 0.96 ± 0.06 mmol/L to 1.23 ± 0.3 mmol/L (mean ± SEM, n = 8, P < .05) with weight reduction. In the two men, plasma HDL cholesterol concentrations were, respectively, 1.22 and 0.65 mmol/L before and 1.23 and 0.98 mmol/L after weight loss. Specific binding of 125I-HDL2 and 125I-HDL3 to purified plasma membranes was determined using abdominal and omental fat depot before and after weight loss in six of the ten obese patients. An average reduction of 30% to 40% in 125I-HDL2 and 125I-HDL3 binding capacity to these membranes occurred after weight loss. Furthermore, a positive correlation (r = .65, n = 10, P < .05) was observed between plasma HDL cholesterol and triglyceride concentrations before weight loss but not after weight loss (r = .01). The changes in plasma HDL cholesterol and plasma triglyceride concentrations following weight loss were also not significantly related (r = .55, n = 10). However the change in plasma HDL cholesterol correlated significantly with the change in HDL2 binding to abdominal subcutaneous adipocyte plasma membranes (r = 0.97, n = 5, P < .01). These results show that reduced plasma HDL cholesterol in obesity is not necessarily associated with hypertriglyceridemia. The increase in HDL cholesterol with weight loss and weight maintenance was gradual and delayed and is therefore not simply the result of acute nutritional adjustments. The reciprocal changes in HDL binding to adipocyte membranes suggest that fat tissue may participate directly in modifying plasma HDL cholesterol in obesity.

A 56-year-old man, the offspring of a consanguineous first cousin marriage, presented with clinical, morphological, and biochemical features of familial deficiency of high-density lipoproteins (Tangier disease). Of 8 first- and second-degree relatives examined, 4 had either plasma apo A-I or HDL cholesterol concentrations 2 standard deviations below normal population mean on at least 1 occasion. The patient and a majority of his relatives also had high plasma apo B concentrations relative to their levels of cholesterol. Adipose tissue biopsy was undertaken to study HDL interaction with the patients' cells. Specific uptake of HDL3 was demonstrated in adipocytes of this patient, but was decreased relative to a control of similar fat cell size. However, no marked difference in fat cell cholesterol content was observed between the Tangier patient and the control. Thus it appears unlikely that adipocytes play a role in the etiology of Tangier disease.

The purpose of the study was to assess the role of adiposity in the enhanced insulin sensitivity observed in endurance athletes (EA). An oral glucose tolerance test (75 g glucose) was administered to nine EA and to 23 sedentary subjects (SS). Two different strategies were used to investigate the problem. First, body composition indicators and Vo2max were correlated with the delta insulin and delta glucose areas measured for 180 minutes following glucose ingestion. These correlation analyses were performed for the two groups combined (n = 32). No significant correlations were observed between either fat weight or percent body fat versus delta insulin, delta glucose or delta glucose/delta insulin areas. Moreover, no significant correlation was observed between the several subcutaneous fat indicators and delta insulin, delta glucose and delta glucose/delta insulin areas. The second strategy consisted of comparing EA to SS when percent body fat difference was eliminated. This was achieved by two different methods, first by covariance analysis and second by comparing subsamples of trained and non-trained subjects paired with respect to percent body fat. These two comparisons revealed that even when adiposity was equal between the groups, a significantly greater insulin sensitivity was observed in the EA group (p less than 0.01). The present results suggest that adiposity is not the determining factor for the increased insulin sensitivity of trained subjects.

The role of the genotype in the response to short-term overfeeding was assessed by submitted six pairs of male monozygotic twins to a 4.2 MJ (1000 kcal) per day energy intake surplus for a period of 22 consecutive days. Individual differences in fat mass and fat-free mass gains were observed in response to overfeeding but they were not randomly distributed. Indeed, the within-pair resemblance in the response was striking when compared to the heterogeneity found among the pairs in adiposity and fat-free mass gains. The intrapair resemblance in the response to overfeeding as assessed by the intraclass coefficient computed with the individual changes, reached 0.88 for total fat mass and 0.76 for fat-free mass. A similar trend for a genetically determined pattern of adaptation to overfeeding was observed for resting metabolic rate (intraclass = 0.63), thermic effect of a meal (intraclass = 0.62), and energy cost of submaximal exercise (intraclass = 0.78) when the data were analysed in terms of changes in oxygen uptake. On the other hand, no major alterations in glucose and insulin response to a glucose load or a test meal, in cardio-pulmonary adaptation to submaximal exercise and in maximal exercise tolerance were found with overfeeding. In contrast, the response of suprailiac fat cell lipolysis (intraclass of about 0.7) and heparin releasable adipose tissue lipoprotein lipase (intraclass - 0.82) varied among individuals but was highly homogeneous within genotypes. Similarly, a genotype-overfeeding interaction effect was seen for serum triglycerides (intraclass = 0.69), HDL-cholesterol (intraclass = 0.85), and the HDL-cholesterol to total cholesterol ratio (intraclass = 0.82). Multiple correlation analyses suggest that much of the variance in the response of fat mass (R = 0.65) and fat-free mass (R = 0.81) is accounted for by alterations in the energy expenditure components assessed in the study. If one takes into account the measurement errors always present in such complex studies and the fact that only a limited fraction of the energy expenditure of activity was considered by design, one can conclude that the genotype determines to a large extent the response variation to short-term overfeeding. In particular, the genotype-overfeeding interaction effect for body composition changes seems to be mediated by the various energy expenditure components, themselves characterized by significant genotype-overfeeding interaction effects.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

In order to study the effects of heredity and of physical training on adipose tissue morphology and metabolism, 15 pairs of monozygotic twins (MZ) (six males and nine females), aged from 16 to 24 years, weighing 56.2 +/- 9.1 kg and with 13.9 +/- 8.2 percent body fat, were submitted to a biopsy of adipose tissue in the suprailiac region. In addition, eight pairs of twins (four male and four female) took part in a 20-week ergocycle training program, five days a week, 40 min a day, at 80 percent of their maximal heart rate. Adipocyte diameter (AD) was assessed on collagenase isolated fat cells. Basal (BL), epinephrine submaximal (10(-5) M) (ESML) and epinephrine maximal stimulated lipolysis (10(-4) M) (EML) were determined on isolated fat cells. Intraclass correlation coefficients indicated significant intrapair resemblance before training for all fat morphological and metabolic indicators (0.78 less than or equal to ri less than or equal to 0.93). Training significantly increased VO2 max (pre: 44.7 +/- 7.6 (ml/kg) vs post: 50.8 +/- 5.0; P less than or equal to 0.001). No training effect was found in percent body fat and AD. Training significantly increased BL, ESML, and EML (P less than or equal to 0.01). Moreover, twins of the same MZ pair yielded identical responses in ESML and EML with training. Intraclass coefficients for the magnitude of change in activity over pretraining values reached 0.84 and 0.90 respectively. Apparently a genetically determined response to training could not be found for BL. These results show that training per se has an effect on adipose tissue lipolysis beyond variation in fatness. Furthermore, sensitivity of stimulated lipolysis to training appears to have a genetic basis.

With the advent of modern therapy, it has become essential to obtain a tissue diagnosis in all cases of pulmonary and mediastinal disease. Since it is often necessary to resort to thoracotomy as a final step in making such a diagnosis, we have sought a procedure that is simpler while capable of providing the same information. Through a standard cervical mediastinoscopy incision, the mediastinum is first explored; if the diagnosis is not obtained, the mediastinal pleura is digitally opened and lung or pleural biopsies are taken. In the course of 1,100 mediastinoscopies since 1969, 275 pleuroscopies have been done. We were able to obtain a tissue diagnosis in 102 (78%) of 131 patients with bronchogenic carcinoma, in 92 (91%) of 102 with benign pulmonary disease, and in all 20 (100%) with pleural disease.

In the 16-year period 1962 to 1978, 409 transaxillary apical pleurectomies were carried out for definitive treatment of spontaneous pneumothorax in 362 patients. Surgical indications included recurrence (336), bilaterality of the disease (23), persistent air leak (22), and nonexpansion of the lung (10). There was 1 operative death (unsuspected brain tumor), and 3 patients required reexploration for clot removal. The average postoperative period of hospitalization was 6 days. Three hundred ten patients (86% of all patients) were contacted for follow-up 1 to 16 years after operation (average, 4.5 years). There were two documented episodes of recurrent ipsilateral pneumothorax (0.6%). Postoperative pulmonary function studies were done in 40 patients (unilateral, 29; bilateral, 11) 2 to 5 years after operation. The results indicate that there are no significant abnormalities compared with predicted values.

In humans, high-density lipoprotein (HDL)-cholesterol ester turnover exceeds that of HDL apoproteins by severalfold or more, suggesting an independent catabolic fate of these constituents. The present study investigated the cellular uptake and dissociation of HDL labeled in its apoproteins with 125I and in its cholesterol ester with [3H]cholesteryl palmityl ether, a nonhydrolyzable cholesterol ester analogue. Approximately 50% of cell-associated 125I-HDL2 and 125I-HDL3 was released from prelabeled adipose cells by incubating the latter in the presence or absence of unlabeled lipoproteins for 2 h. The uptake of HDL-cholesterol ester by human fat cells as reflected by [3H]cholesteryl palmityl ether was 5-18 times greater than that predicted from the uptake of 125I-HDL2 and 125I-HDL3 and was irreversible. Analysis of dissociated 125I-HDL3 demonstrated changes to both higher and lower density fractions compared with the starting material. There was a high correlation between the cellular uptake of HDL3-cholesterol ester and HDL3-apoprotein uptakes (r = 0.90, P less than 0.01), suggesting that HDL-cholesterol ester uptake requires a specific apoprotein interaction or binding step. The selective uptake and retention of HDL-cholesterol ester by isolated adipocytes implies that human fat tissue may play a role in regulating the lipid composition of plasma HDL.

The Medtronic Intact valve is a third-generation porcine bioprosthesis produced using a leaflet fixation process which imposes virtually zero hydrostatic pressure. This fixation method provides optimal preservation of the original leaflet structure and integrity and should result in an improvement in durability compared to conventional preservation techniques. The biomechanical basis for this hypothesis is presented along with early experience with 118 patients (125 valves). There have been no complications related to primary valve failure and the incidence of other valve related events is acceptable.

The objective of this study was to identify individuals of the same age, sex, activity level and fat-free mass who differed in their level of energy intake (EI). Estimates of energy intake and physical activity level were derived from three-day food and activity records from 430 individuals 17-54 years of age. Body composition was measured by underwater weighing and body fat and fat-free mass were obtained. Subjects were grouped into four categories based on age and sex (females aged 17-34 and 35-54 years and males aged 17-34 and 35-54 years). Subjects were identified as small eaters (SE) or large eaters (LE) according to kJ of EI per kg body weight, SE being from the lower quartile and LE from the upper quartile of their distributions. The results showed that, on average, LE consumed almost twice as many kJ per kg body weight as SE (about 200 versus 100). In addition middle-aged male and female SE were significantly (P less than 0.001) heavier than middle-aged male and female LE respectively. The mean body weight for the male SE was 82 +/- 12 kg (mean +/- s.d.) against 69 +/- 9 kg for the LE, while it was 66 +/- 10 kg against 52 +/- 5 kg for the female SE and LE. The male and female SE also had a significantly higher percentage body fat in both age groups. In general, there was no difference in fat-free mass and activity level between the SE and LE. It is concluded that there exist groups of individuals who have a considerable difference in their EI and adiposity even though they have similar levels of activity and fat-free mass.

PURPOSE The main purpose of the present investigation was to test whether and to what extent familial/genetic factors are involved in the changes of postheparin lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in response to exercise training. Additional hypotheses were also tested as to whether there were familial/genetic factors shared by baseline and the corresponding response to exercise training (i.e., by baseline triglyceride (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B)) and deltaPH-LPL activity). METHODS Serum TG and PH-LPL were measured in 459 subjects from 99 sedentary Caucasian families of the HERITAGE Family study before (baseline) and after completing a 20 wk (3 times per week) exercise training protocol. The training protocol had a target intensity of 75% of the heart rate associated with baseline VO2max during the last 6 wk. PH-LPL activity was measured in the study subjects. Both univariate and bivariate familial correlation analyses were applied to the baseline and response data. RESULTS The maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%, respectively. There were no common familial factors for TG(B) and deltaTG, nor were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were common familial factors underlying deltaTG and deltaPH-LPL; these familial factors seemed to differ across sex and generation groups. CONCLUSION Although there were no common familial factors underlying the covariation between the baseline triglyceride and PH-LPL activity and the corresponding responses to exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the deltaTG and deltaPH-LPL covariation apparently share some common familial determinants.

Freshly isolated human adipocytes showed specific uptake of 125I-labeled human high density lipoprotein (HDL2 and HDL3), a portion of which could be released by subsequent incubation with excess unlabeled ligand. To study the mechanism of HDL binding, sucrose gradient-purified adipocyte plasma membranes were incubated with radioiodinated lipoprotein particles under equilibrium conditions in the absence (total binding) or presence (nonspecific binding) of 100-fold excess unlabeled ligand. Specific binding of HDL2 and HDL3, calculated by subtracting nonspecific from total binding, was Ca++ independent, unaffected by EDTA, and not abolished by pronase treatment of the membranes. Modification of HDL3 by reductive methylation or cyclohexanedione treatment also failed to affect its binding to adipocyte plasma membranes. High salt concentration (200 mM NaCl) inhibited specific binding of HDL2 and HDL3 but had no effect on LDL binding. A significant portion of 125I-HDL2 or 125I-HDL3 binding was consistently inhibited by adding excess unlabeled LDL, but this inhibition was incomplete as compared with a similar molar excess of unlabeled HDL2 or HDL3. The role of apoproteins (apo) in HDL binding to adipocyte membranes was examined by comparing binding of HDL2 and HDL3 isolated from normal, abetalipoproteinemic (abeta) and apo E-deficient (apo E0) plasma. Specific binding was observed with all normal and mutant HDL particles. Furthermore, a significant portion (61-78%) of abeta-HDL2, apo E0-HDL2, and apo E0-HDL3 binding was inhibited by adding 100-fold excess of unlabeled low density lipoproteins (LDL). The cross-competition of LDL and HDL binding was confirmed by the ability of normal, abeta, and apo E0-HDL2 to completely inhibit 125I-LDL binding. These data suggest that HDL binding is independent of apo E and that the responsible apoprotein(s) of HDL complete with LDL-apo B for binding to the same or closely related site in the adipocyte plasma membrane. Normal and apo E0-HDL3 binding was also completely inhibited by normal HDL2, which suggested that HDL2 and HDL3 probably bind to the same site. Scatchard analysis of normal HDL2, normal HDL3, and apo E0-HDL3 binding data best fitted a one-component binding profile with similar equilibrium dissociation constants (40-96 nM). HDL3 binding was found to be effectively inhibited by anti-human apo AI or anti-human apo AII, but not by anti-human apo B antisera. This binding was also unaffected by monoclonal anti-human apo B or E antibodies known to inhibit binding of apo B or apo E containing lipoprotein to the LDL receptor of cultured fibroblasts. These findings, taken together, suggest that human fat cells possess HDL binding sites with apo AI and /or apo AII specificity. The significant but partial inhibition of HDL2 and HDL3 binding by LDL along with the complete inhibition of LDL binding by HDL2 and HDL3 tends to exclude a single binding site that interacts both lipoproteins and favors the interpretation that LDL and HDL particles bind to multiple recognition sites or to different conformation of the same lipoprotein binding domain on the human fat cell.

The digestive tract contains endogenous cannabinoids (anandamide and 2-arachidonylglycerol), enzymes involved in their synthesis and metabolism and cannabinoid receptors. CB1 receptors are mainly expressed on myenteric and submucosal nerve plexuses and their activation results in inhibition of neurotransmitters (mainly acetylcholine) release. CB2 receptors are mainly expressed on cells of immune system, with a possible role in pathophysiological states (e.g. inflammation). Action of cannabinoids in the digestive tract include inhibition of intestinal motility, gastric and intestinal secretion, inflammation, visceral pain and cell proliferation. Experimental evidence also suggests that anandamide (an orexic fatty acid ethanolamide) in the gut may act as a “hunger signal”, an action which could be counterbalanced by intestinal oleoylethanolamide (an anorexic fatty acid ethanolamide).