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Basic Remarks: The frequency of overweight, together with the associated increase in morbidity--in particular coronary heart disease--means that such patients often require intensive care., Main Points Discussed: The particular features of intensive care of obese patients are the increased risk of aspiration pneumonia (in the presence of lowered pH and elevated gastric juice volume), respiratory insufficiency caused by a reduction in expiratory reserve volume, and a greater incidence of thrombosis and embolism. Ventricular hypertrophy and dilatation results in a reduced cardiac reserve. A clinically unrecognized insulin resistance may become manifest during intensive care. Digoxin, theophylline and aminoglycosides, commonly with a low therapeutic spectrum, when administered on the basis of weight, may lead to dangerously high serum concentrations in the overweight., Conclusions: At a weight of more than about 100 kg, it must generally be expected that the compensatory mechanisms of the body are exhausted and that there will be an increased susceptibility to additional disorders of homeostasis.

Problem: With respect to prevention of its most common complication--mortality from coronary heart disease--treatment of hypertension had disappointed. It is possible that this is due to negative effects of antihypertensives on lipid metabolism., Major Topics: The effects of beta blockers on lipid metabolism can be differentiated principally, in accordance with the classification of beta blockers into those with and those without intrinsic sympathomimetic activity (ISA), as also selectivity and non-selectivity. Thus, non-selective beta blockers with no ISA usually lead to an increase in triglycerides of 25% to 30%, and a decrease in HDL cholesterol of about 15%. On average, beta-1 selective blockers result in a smaller increase in triglycerides. Beta blockers with ISA, in contrast, are largely neutral vis-à-vis lipid metabolism. In the individual case, in particular in the presence of hyperlipoproteinemia, the effects cannot be reliably predicted., Conclusions: Lipoprotein concentrations should be monitored during treatment with beta blockers. If necessary, a change in the agent employed is recommended. In the case of prevention of a second myocardial infarction, for which various studies have unequivocally shown a reduction in mortality associated with treatment with beta blockers with no ISA, these side effects will, however, be accepted--with the exception of extreme changes--for a limited period of time.

Primary familial forms of chylomicronemia can lead to acute life-threatening complications, especially acute pancreatitis. The main aim of therapy is to avoid this so-called chylomicronemia syndrome. In 12 patients with primary chylomicronemia due to familial hypertriglyceridemia, the addition of 2.16 g omega-3 fatty acids over 4 weeks and 4.32 g for 8 weeks resulted in a decrease of serum triglyceride levels from 1,624 +/- 333 to 894 +/- 241 mg/dL after 12 weeks. Cholesterol and triglyceride levels in the chylomicron fraction were reduced concomitantly, the apolipoprotein B-100/B-48 ratio increased, very--low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol, and total cholesterol levels decreased, and low-density lipoprotein (LDL) cholesterol showed a tendency to increase, but this finding did not reach significance. High-density lipoprotein (HDL) cholesterol levels remained unchanged, as did the levels of apolipoproteins A-I, A-II, and E, and lipoprotein(a). Apolipoprotein B levels decreased significantly. The decrease of triglyceride levels to still-elevated concentrations was accompanied by a substantial decrease in plasma and whole-blood viscosity and erythrocyte aggregation, which reached normal values. As in chylomicronemia, complications usually occur at triglyceride levels higher than 1,500 mg/dL; patients can still profit from treatment with omega-3 fatty acids, even though triglyceride levels are still substantially elevated. No clinically relevant side effects occurred, with the exception of the manifestation of diabetes mellitus in one patient, which could be reversed after discontinuation of treatment.

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.

Obesity and an android body fat distribution are related to metabolic disorders. We investigated the interdependences between metabolism, overweight, and body fat distribution in 40 moderately obese men before and after weight-loss. Correlations between metabolic parameters and body mass index (BMI) or waist to hip ratio (WHR) were much weaker in this exclusively obese population than in subjects of all weight categories, but the association between BMI and glucose tolerance (r = -.46, P less than .01) increased significantly after weight-loss. The improvement of metabolic parameters was much stronger in men who achieved normal weight (BMI less than 27 kg/m2) than in those who remained obese (BMI greater than 30 kg/m2, P less than .05). The WHR decreased during the diet (P less than .001), and this decrease and the extent of weight-loss were significantly correlated to an increase in insulin sensitivity (r = -.41, P less than .01) and a decrease in glucose area after an oral glucose load (r = .34, P less than .05). The decrease in apolipoprotein B, total cholesterol, and low-density lipoprotein (LDL) cholesterol was significantly correlated only to the extent of weight-loss (r = .34, .31, and .39, respectively; P less than .05). We conclude that it is best to reach normal weight for the normalization of metabolic aberrations. The reduction of cholesterol appears to be dependent on the extent of weight-loss, while the improvement in insulin sensitivity and glucose tolerance apparently is related to both the extent of weight-loss and to a change toward a less android body fat distribution.

Cholesterol determinations of 15.391 inhabitants of Leipzig were carried out in November 1990 within the Bavarian Cholesterol-Screening-Project. The aim of this screening on population basis was to identify individuals with elevated blood cholesterol levels as one of the risk factors of atherosclerosis. Capillary blood cholesterol was measured by means of the Reflotron dry-chemistry system (Boehringer, Mannheim). 27% of the inhabitants of Leipzig show cholesterol levels lower than 5.2 mmol/l as recommended by the European Society of Atherosclerosis Research. Furthermore the characteristic age dependence is seen. In comparison with the town Nürnberg lower mean cholesterol values were found in Leipzig.

Objective: In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful., Research Design and Methods: Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123I-labeled antibodies against granulocytes (n = 11)., Results: Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods., Conclusions: In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method.

Aims: Description of the effects of major cis and trans fatty acids on serum lipoproteins., Main Points Discussed: Trans fatty acids are formed in particular during industrial hydrogenation of oils and fats. Elaidic acid, the most important of the trans fatty acids, has an unfavorable effect on lipid metabolism that results in a negative shift of the HDL/LDL quotient. Nevertheless, due to the low concentrations in a balanced diet, its effects are only slight, and fall within the biological range of fluctuation., Conclusions: The biological effect of fatty acids varies from one class to another (saturated, mono-unsaturated, poly-unsaturated). A more accurate differentiation would be desirable. On the other hand, the overall effect of the trans isomers of fatty acids on the organism as a whole is small, so that it does not need to be discussed, for example, in dietary counseling.

Possible metabolic changes during chronic treatment is of specific importance for the development of antihypertensive drugs. The impact of a combination treatment with co-dergocrine mesilate/nifedipine (Pontuc; CAS 8067-24-1 resp. CAS 21829-25-4) on the lipid metabolism as well as hematological and biochemical values was evaluated in a group of hypertensive patients. HDL-cholesterol remained unchanged, whereas total cholesterol and LDL-cholesterol slightly decreased, apoprotein AI increased and apoprotein B decreased. In conclusion the results of this study indicate that co-dergocrine mesilate/nifedipine has no negative impact on the lipid metabolism in patients with essential hypertension.

The effects of the HMG CoA reductase inhibitors lovastatin and pravastatin on serum lipids, lipoproteins and apolipoproteins have been studied in 35 patients with primary hypercholesterolaemia. LDL cholesterol was lowered to the same extent by both agents compared on a mg basis of each drug per day. HDL cholesterol was increased by lovastatin but not by pravastatin. The reduction in serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced after lovastatin than pravastatin. After 1 year the effect of combined treatment with 40 mg pravastatin and 8 g cholestyramine on the reduction in LDL cholesterol (-39%) in 13 patients was comparable to that of 80 mg lovastatin plus 8 g cholestyramine (-40%) in 12 patients with identical baseline values. Differences were also found in the effects of the combination therapy with the two drugs on HDL cholesterol, serum triglycerides, VLDL triglycerides, VLDL cholesterol, and apolipoproteins.

Android obesity is reported to be a risk factor for coronary heart disease and aberrations in lipid metabolism, but so far its association with other risk factors such as age and overweight has not been clearly analyzed. We therefore investigated the relationship between the waist-to-hip ratio, age, body mass index and serum lipoproteins in 305 probands (158 men, 147 women), while body mass index was kept constant in all age groups. Waist-to-hip ratio correlated with both age (r = 0.441) and body mass index (r = 0.532) in simple linear correlation analysis (P less than 0.001). In stepwise multiple regression analysis we found in both sexes a first step dependence on age for total and LDL-cholesterol (P less than 0.001), a first step dependence on waist-to-hip ratio for triglycerides (P less than 0.001), VLDL-triglycerides (P less than 0.001) and VLDL-cholesterol (P less than 0.001 for men, P less than 0.05 for women), and an inverse first step dependence on body mass index for HDL-cholesterol (P less than 0.05 for men, P less than 0.001 for women). From these results we propose an independent association between waist-to-hip ratio and triglycerides while the relation to total and LDL-cholesterol is determined by age. HDL-cholesterol, on the other hand, is influenced by body fat mass and independent from age or body fat distribution.

It is speculated that endogenous opioid peptides are involved in glucose metabolism and that their homeostasis might be disturbed in obesity. Despite a different response of the pancreatic beta-cells after beta-endorphin and naloxone injections between obese patients and normal weight controls, there is little knowledge concerning the direct influence of a glucose load on beta-endorphin plasma levels, especially with respect to various nutrition states. During exploration of this topic we gained further insight on the difference of basal beta-endorphin plasma levels between normal and overweight persons. We compared beta-endorphin plasma levels during an oral glucose load in 60 obese, non-diabetic patients and in 20 normal weight controls. We also studied 40 of the obese patients after a weight reduction of 2.1 kg/m2. The following results were obtained: (1) Normal weight females have significantly lower (P less than 0.05) basal beta-endorphin levels compared to the male controls. This difference in gender is abolished in obesity where female and male patients do not differ in basal beta-endorphin plasma levels. Therefore, the difference between normal and overweight persons in beta-endorphin plasma levels was restricted to the subgroup of females. We suppose that former neglect of this difference in gender explains most of the so far reported discrepant results. (2) During the oral glucose tolerance test the beta-endorphin plasma values remained constant in the obese group. Despite improved insulin sensitivity after weight reduction there was still no change of beta-endorphin plasma levels both during the OGTT and when compared to the values before weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

We describe the occurrence of a liver adenoma in a young patient with Klinefelter's syndrome, diagnosed by classic 47,XXY karyotype in all investigated cells and a sex hormone imbalance. To our knowledge, this is the first report of such an association, which might suggest a simple coincidence. However, a pathogenetic link between Klinefelter's syndrome and liver adenoma can be suggested in view of the following facts: Liver adenoma mostly affects women of child-bearing age using oral contraceptives. It is very rare in men, and affected men frequently have been treated with androgens. Both groups are characterized by a sex hormone imbalance. Also, the risk of breast cancer, another hormone-sensitive tumor, is greatly elevated in men with Klinefelter's syndrome, possibly due to sex hormone imbalance.

The effects of the HMG-CoA reductase inhibitors lovastatin and pravastatin were studied over 4 months on serum lipids and lipoproteins in 35 patients with severe primary hypercholesterolaemia. In 17 patients 20 mg of lovastatin/day lowered the total cholesterol level by 18% (baseline 373 mg/dl) and LDL cholesterol by 20% (baseline 300 mg/dl). The corresponding data for 40 and 80 mg of lovastatin/day were respectively -23% and -29% for total cholesterol, and -30% and -36% for LDL cholesterol. Pravastatin at 20 mg/day lowered the total cholesterol in 18 patients by 20% (baseline 373 mg/dl) and LDL cholesterol by 24% (baseline 307 mg/dl). The corresponding data for 40 mg of pravastatin per day were 24% for total cholesterol and 30% for LDL cholesterol. So the effects of both HMG-CoA reductase inhibitors on total and LDL cholesterol are comparable. HDL (high-density lipoprotein) cholesterol was increased by lovastatin, whereas pravastatin showed no influence on HDL cholesterol. The reduction of serum triglycerides, VLDL triglycerides and VLDL cholesterol was more pronounced under treatment with lovastatin than under pravastatin.

The connection of body fat distribution (BFD) and the risk of developing mammary, cervical, endometrial or ovarian carcinoma was ascertained for 163 patients with carcinoma (mean age 49.9 [19-78] years) and 489 controls of comparable age and body-mass index. BFD was expressed as the ratio of waist and hip circumference (T/H ratio of 0.822 vs 0.781 and 0.826 vs 0.789, respectively; P less than 0.01). In premenopausal women with mammary or cervical carcinoma and in all postmenopausal women BFD was similar to that in the control subjects. A common cause of android obesity and ovarian or endometrial carcinoma may be a reduction of sex-hormone-binding globulins with an elevated serum level of free androgens and oestrogens.

Four patients (two men and two women, aged between 54 and 75 years), known to have type II diabetes since two to twenty years, had for several months been suffering from segmental pain of thoracoabdominal or lumbosacral distribution. Diabetic radiculopathy was confirmed by paravertebral electromyography. Analgesics having brought insufficient relief, treatment with an insulin infusion pump was commenced. The pains disappeared within 2-14 days. Even when the infusion treatment was no longer used, pains did not recur under an euglycaemic regimen. These results suggest that the transitory use of insulin infusion by pump can be a worthwhile therapeutic alternative in diabetic radiculopathy.

Atherosclerosis is the main cause of death in diabetes mellitus. This may at least in part be due to lipoprotein abnormalities which have been described in these patients. Apolipoprotein-E is a component of most lipoprotein fractions and plays an important role in the catabolism of VLDL. The different apolipoprotein-E phenotypes determined genetically are associated with certain hyperlipoproteinemias in a various degree in nondiabetic patients. In most cases apolipoprotein-E phenotype E2/2 is characteristic for familial dysbetalipoproteinemia. Phenotype E3/2 was found to be more frequent in hypertriglyceridemia while phenotype E4/3 was associated with hypercholesterolemia as well as with type V hyperlipoproteinemia. We studied apolipoprotein-E phenotypes and serum lipids in 141 type II diabetic patients (36 normolipidemic 41 type IIa hyperlipidemic, 32 type IIb hyperlipidemic, 24 type II hyperlipidemic, 8 type V hyperlipidemic). the phenotype E3/3 was more common in normolipidemic diabetic (77.8%) than in hyperlipoproteinemic diabetic patients (42.9%) or in the control group (57.5%). On the other hand phenotype E3/2 was more frequent in hypertriglyceridemic (50%) than in normolipidemic (5.6%) or hypercholesterolemic (hyperlipoproteinemia IIa: 4.9%, IIb: 9.4%) diabetic patients. The phenotype E4/3 was more frequent in all hyperlipoproteinemic diabetic patients, especially in those having hypercholesterolemia (34.2%) or mixed hyperlipidemia (50%). In conclusion we found a strong association between apo-E2 and hypertriglyceridemia in diabetic patients. This association was stronger than the one found in the general population. The association between apo-E4 and hypercholesterolemia in diabetic patients was similar to the one described in non-diabetic patients. We therefore conclude that type II diabetes mellitus is a possible cofactor in the apolipoprotein-E2 associated hyperlipoproteinemia.

Epidemiological studies have identified lipoprotein (a), which has been known since 1963, but has received attention only recently, as a further risk factor for premature arteriosclerosis. This substance is similar to low-density lipoprotein, but it's serum concentration (and thus the increase in risk) is genetically determined and highly variable from one individual to another. The usual dietary and drug measures have only little effect on lipoprotein (a) serum levels. Although the physiological significance of lipoprotein (a) is unknown, it shows great homology to plasminogen, and thus might represent a link between arteriosclerosis and thrombosis.

beta-Lipotropin, a pituitary peptide, is a potent stimulator of lipolysis in rabbit adipose tissue in vitro and in vivo. Insulin inhibited the beta-lipotropin (1-100 nM)-stimulated glycerol release from rabbit adipocytes and fat pads significantly at concentrations of 10 and 100 microM. Both these concentrations of insulin also decreased the degradation of beta-lipotropin in intact adipose tissue to the same extent as the lipolytic activity. Furthermore, insulin reduced the degradation of beta-lipotropin in rabbit adipose tissue homogenate. Like insulin, several lysosomotropic agents also decreased significantly the degradation and the lipolytic activity of beta-lipotropin. On the other hand, insulin-like growth factor I in lower concentrations (1-100 nM) did not effect degradation and lipolytic activity of beta-lipotropin in rabbit adipose tissue. Thus, a direct influence of insulin on lysosomal enzymes degrading beta-lipotropin in rabbit adipose tissue can be suggested.

beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.

Lipoprotein (a) is believed to be an independent risk factor for atherosclerosis. Fat modified diets or lipid lowering drugs seem to have little effect on Lp(a) serum levels. We tested the possibility of lowering Lp(a) by weight reduction and examined the correlation between Lp(a) serum levels, other lipoproteins, body weight and body fat distribution in 53 obese patients. Weight reduction by a 4000 kJ protein enriched diet for four weeks led to a mean 19 percent reduction of Lp(a) serum levels in men (P less than 0.01) and a mean 30 percent reduction in premenopausal women (P less than 0.001). Significant correlations could neither be demonstrated between Lp(a) and other lipoproteins nor between initial Lp(a), overweight and body fat distribution. This implies that an intraindividual interdependence between Lp(a) and body weight seems to be possible although an interindividual correlation can not be shown.

Blood pressure and serum lipoprotein concentrations were assessed in 40 men with essential hypertension at the end of a long-term, controlled intervention study (HAPPHY) after 5.2 +/- 1.4 years of treatment with hydrochlorothiazide (n = 23) or atenolol (n = 17) and after a wash-out period. After withdrawal from antihypertensive medication, the blood pressures of patients treated with diuretics or beta blockers rose from 142/93 and 145/91 to 159/106 and 165/104 mm Hg, respectively. At the same time, low density lipoprotein cholesterol decreased by 17 and 12 mg/dl, respectively, in the diuretic and beta blocker groups (p less than 0.05). In addition, total cholesterol decreased by 16 mg/dl (p less than 0.05) in the diuretic group, whereas high density lipoprotein cholesterol increased by 8 mg/dl (p less than 0.01) and triglycerides decreased by 27 mg/dl (p less than 0.05) in the beta blocker group at the end of the wash-out period as compared to the final phase of the HAPPHY study. The data indicate the persistence of lipid changes during long-term treatment with hydrochlorothiazide and atenolol. For the first time, it was clearly demonstrated that the well-known unfavorable effects of diuretics and beta blockers on lipid metabolism are reversible after cessation of long-term therapy of several years' duration.

To find out, whether microheterogeneity of neurophysins is due to aging of neurosecretory granules we investigated neurophysin proteins of porcine origin from newly formed and aged granules, as well as from two different extraction methods from whole posterior pituitary glands by high performance liquid chromatography. In newly formed as well as in aged granules all microheterogeneous forms of the neurophysins were present in nearly identical relation suggesting that microheterogeneity is not due to maturation or post matural degradation. In comparison, the crude material obtained by the method of Uttenthal and Hope showed a comparable content of the different neurophysins while Chauvet's method resulted in a different HPLC pattern. In summary, neurophysin heterogeneity is obviously not due to aging processes.

Porcine neurophysin proteins as well as oxytocin and lys-vasopressin were extracted from fresh (immediately after death) and stored (10, 20 and 60 min, 6, 12 and 24 hours) pituitary posterior lobes. Analyses were performed by high performance liquid chromatography (HPLC). In fresh tissue all forms of neurophysin proteins were present, the pattern of distribution of the neurophysins, oxytocin and lys-vasopressin did not change during the period of storage while other unknown peaks showed degradation. Posterior pituitary glands can be used for the preparation of neurophysin proteins, oxytocin and lys-vasopressin within 24 hours after death.

Melanotropin potentiating factor (MPF) potentiates the melanotropic activity of melanocyte stimulating hormones. Although the message sequence for the melanotropic and lipolytic activity are identical for beta-lipotropin, alpha- and beta-MSH, MPF was not able to affect the lipolytic response to alpha- and beta-MSH in rabbit adipocytes. However, MPF at concentrations of 10-5 and 10-6 mol/l inhibited the lipolytic activity of beta-lipotropin. This suggests that the inhibition of the lipolytic response to beta-lipotropin is not connected with the common lipolytic message sequence (beta-LPH 47-53). Since beta-lipotropin has a second lipolytic sequence in its C-terminal part this second lipolytic core of beta-lipotropin might interact with MPF which has no intrinsic lipolytic activity.

Peptide hormones are potent stimulators of lipolysis in incubated adipocytes or adipose tissue of laboratory animals. However, none out of 40 synthetic or highly purified peptide hormones or sequences from the pituitary, the gastrointestinal tract and of different origin was able to stimulate glycerol release from 'incubated' human adipocytes. Yet, this model of the 'incubated adipocyte' offers several disadvantages: rapid decrease of pH in the incubation medium, release and increment of lipolysis inhibiting substances such as FFA and adenosine and rapid unspecific degradation of the peptides. In an improved in vitro model--pH-stat titration--which avoids or diminishes the disadvantages of 'incubated adipocytes', a group of pituitary peptides was tested. One peptide hormone, beta-lipotropin, stimulated lipolysis significantly in human adipose tissue. Two other peptides which were highly active in adipose tissue of laboratory animals were ineffective in this system too. The lipolytic response to beta-lipotropin was comparable to the effect of noradrenaline at equimolar concentrations. The data indicate that results on the lipolytic activity of peptide hormones in adipose tissue of laboratory animals cannot be transferred to human adipose tissue. In advanced in vitro test systems the ability to stimulate lipolysis could also be shown for a peptide hormone suggesting a role of such substances in the endocrine regulation of adipose tissue mass in men.

No reliable answer can yet be given whether the pituitary gland is physiologically involved in the process of fat mobilization. The reasons are, for example, different test systems and criteria of lipolytic activity as well as variable criteria of purity of the peptides tested. Under comparable test conditions MSH, beta-endorphin, ACTH and beta-lipotropin turned out to be the most lipolytically active peptides. There is also increasing evidence that these peptides are involved in metabolic processes especially in glucose metabolism. The lipolytic activity of beta-lipoprotein, ACTH and MSH is mediated by a common heptapeptide (beta-LPH 47-53) furthermore, beta-lipotropin has a second message sequence in the C-terminal part of its molecule (beta-endorphin). This second message sequence is located in the amino acid sequence beta-LPH 77-86. The lipolytic effect of all these peptides is accompanied by an activation of adenylate cyclase. The effect of beta-endorphin is not mediated by an opiate receptor. The further elucidation of the lipolytic activity of these peptides investigations were necessary on the degradation of the peptides at the site of action as well as the use of test systems nearer to physiological conditions for example perifused fat cells. In conclusion, there are condensing data on the possible physiological role of brain and pituitary peptides in metabolic regulation.

There is evidence for involvement of gastrointestinal hormones in pathogenesis of obesity and reports on lipolytic activity in animals. The in vitro lipolytic activity of these hormones was tested in human adipocytes. Vasoactive intestinal polypeptide, glucagon, secretin, human gastrin I, gastrin releasing polypeptide, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, bombesin, neurotensin, C-peptide, as well as cholecystokinin did not stimulate lipolysis significantly above basal. These results indicate that the involvement of these hormones in obesity in man might not be due to a direct lipolytic effect on the human adipocyte.

Four lipolytic active centers were localized in proopiomelanocorticotropin (POMC): in the N-terminal part of POMC ("tryptophane rich peptide"), in the N-terminal part of adrenocorticotropic hormone, in the middle portion of beta-lipotropin and in the C-terminal part of beta-lipotropin. The weak lipolytic activity of the "tryptophane rich peptide" is not mediated by its two partial sequences gamma-MSH and delta-MSH. The minimal amino acid sequence for obtaining lipolysis from the N-terminal part of ACTH was ACTH 4-10. Lengthening of this amino acid sequence on the N- or C- terminus resulted in a strong increase of lipolytic potency. The minimal effective sequence from the middle portion of beta-lipotropin was located in the amino acid residues 47-53 which are identical to ACTH 4-10. Additional amino acids on the N- and C-terminus (beta-lipotropin p 41-58 and beta-lipotropin h 35-56) lead also to increased lipolytic activity. The forth center of POMC resides in the C-terminal part of beta-lipotropin (residues 78-91) because sequences from the N-terminal part of beta-lipotropin 61-91 were ineffective. The order of potency of POMC peptides especially in respect to the minimal effective concentration was ACTH 1-13 (alpha-MSH) greater than beta-lipotropin p greater than ACTH greater than ACTH 1-10 greater than beta-lipotropin p 61-91.