Multiple symmetric lipomatosis: clinical aspects and outcome in a long-term longitudinal study.

BACKGROUND: Multiple symmetric lipomatosis (MSL) is a rare disease characterized by the growth of uncapsulated masses of adipose tissue. MSL is associated with high ethanol intake and complicated by somatic and autonomic neuropathy and by the infiltration of the adipose tissue at the mediastinal level. To date, the disease is considered as slowly progressive, but long-term longitudinal data are still lacking. In this study, a long-term follow-up of a large series of MSL patients is presented. METHODS: We studied 31 patients with MSL (30 males and one female) first evaluated at our institution from 1973 to 1992. All patients were followed until 1998-1999 or until death, with a mean follow-up of 14.5+/-5.0 y (range 4-26 y). Both at baseline and during follow-up, the location and the size of the subcutaneous lipomatous fat depots, the presence and the extension of deeply localized lipomatous tissue, and the presence and the severity of both somatic and autonomic neuropathy were evaluated. RESULTS: Eight MSL patients died during follow-up (25.8% of patients). A sudden death was proved to be the cause of death in three patients. All these three patients had severe autonomic neuropathy and none had coronary disease, acute myocardial infarction or other cardiac abnormalities. No signs or symptoms of coronary heart disease were present in the whole series. In addition to this high fatality rate, a substantial morbidity related to the occupation of the mediastinal space by the lipomatus tissue and to somatic neuropathy was also observed. CONCLUSIONS: MSL is associated with a significant morbidity and mortality. Therefore, the definition of 'benign symmetric lipomatosis', still adopted by several authors, cannot be justified.

Fat body of the frog Rana esculenta: an ultrastructural study.

In the frog, the fat body is the largest body lipid deposit and is associated with the gonad. The aim of the present work was to investigate the fine structure of the fat body at different periods of the annual cycle and during prolonged starvation. Results indicate that fat body cells of Rana esculenta caught in autumn and after winter hibernation resemble mammalian adipocytes of white adipose tissue and contain markers of adipose tissue, such as S-100 protein and lipoproteinlipase. However, unlike mammalian adipocytes, fat body adipocytes consistently show small lipid droplets associated with their single, large lipid deposits, a lack of a definite external lamina, and the presence of cellular prolongations and spicula at their surfaces. Transmission and scanning electron microscopy in association with lanthanum tracer experiments suggest that in fat body adipocytes a vesicular-tubular system connects the cytoplasm and the interstitial space. In June (i.e., during the reproductive period), fat body adipocytes appear to have lost much of their lipid deposit and adjacent adipocytes show interdigitation of their plasma membranes and prominent Golgi complexes. In starved frogs, fat body cells can be almost devoid of lipid and in regression to a near-mesenchymal state. Nevertheless, these fat bodies still contain lipoproteinlipase activity (approximately 45% of that found in lipid-filled ones), indicating persistent adipose differentiation of the cells therein. Results presented here show that the R. esculenta fat body is an adipose organ undergoing reversible extreme changes in adipocyte fat content, which are associated with definite ultrastructural features. The fat body represents a suitable model for studying adipose tissue under different and extreme physiological conditions.

Omental and epigastric adipose tissue lipolytic activity in human obesity. Effect of abdominal fat distribution and relationship with hyperinsulinemia.

It has been shown that visceral obesity is associated with an increased incidence of hyperinsulinemia. In such a condition, hyperinsulinemia could be due to an increased lipolytic activity of omental adipose tissue (AT), through an enhanced portal flux of FFA. The purpose of our study was to evaluate the lipolytic activity of omental and epigastric AT obtained from morbid obese patients either with prevalently visceral or subcutaneous abdominal fat accumulation, evaluated by computerized tomography. The relationship between plasma insulin values and in vitro lipolytic activity in both tissues was studied. Thirteen visceral (VO) and 13 subcutaneous (SO) obese patients, matched for sex and body mass index, undergoing vertical banded gastroplasty, were studied. Before surgery, in each patient an OGTT was performed. During surgery, samples of epigastric subcutaneous and omental AT were obtained for evaluation of fat cell weight (FCW) and basal, noradrenaline 10(-5)M and isoprenaline 10(-5) M induced lipolytic activities. No significant differences in basal lipolysis were found between the two types of obesity, both in omental and in epigastric AT. In omental AT, a higher noradrenaline and isoprenaline induced lipolysis was observed in VO than in SO. Isoprenaline induced lipolysis of omental AT (expressed per cell surface area) correlated directly with FCW. VO patients showed plasma insulin values after OGTT significantly higher than SO patients. In the whole group of patients, independently from fat distribution, significant correlations were found between the incremental areas of the plasma insulin curve during OGTT and the noradrenaline an isoprenaline induced lipolytic activities both in omental and epigastric adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of abdominal fat distribution in obese patients: anthropometry versus computerized tomography.

The accuracy of waist to hip girth ratio (WHR) in assessing visceral/subcutaneous abdominal fat distribution has not yet been clearly established in the obese population. The purpose of the present study was to evaluate the relationship between WHR and visceral/subcutaneous fat distribution, both assessed by computerized tomography (CT), in a group of 28 obese patients (15 male, 13 female). Furthermore, 33 normal weight or slightly overweight subjects (23 male, 10 female) were studied as a control group. Obese subjects of both sexes were found to have higher values of WHR than non-obese; conversely visceral:subcutaneous fat area ratio (VSR) values did not differ significantly. Significant correlation between WHR and BMI was present both in males (r = 0.41, P < 0.01) and in females (r = 0.54, P < 0.01). In normal weight males significant correlations between WHR and visceral fat area or VSR were found. In obese males these correlations were much weaker. In normal weight females a significant correlation was found between waist circumference and visceral fat area, whereas in obese females no positive correlations were found between anthropometric measurements and CT indices of visceral fat distribution. In conclusion, WHR cannot be considered as a reliable index of visceral/subcutaneous fat distribution in obese patients, particularly if they are females.

Lipoprotein sub-fraction levels and composition in obese subjects before and after gastroplasty.

Obesity is frequently associated with several alterations of plasma lipid levels and lipoprotein metabolism. To evaluate the effects of severe obesity and weight loss on plasma lipoprotein sub-class levels and composition 11 grossly obese patients were examined before and six and 12 months after gastroplasty. Plasma lipoproteins were isolated by ultracentrifugation in a zonal rotor under rate flotation conditions. Mean body weight was 121.9 kg before gastroplasty, 97.6 kg after six months, and 90.7 kg after 12 months. Total plasma cholesterol was not affected by the weight reduction. Obese patients were characterized by increased levels of IDL and small dense LDL (LDL3). LDL levels, but not LDL3, were reduced following weight reduction. Plasma apo B levels of obese patients were always higher than in controls and were not affected by the weight reduction. After 12 month's weight loss total HDL cholesterol increased without modification of HDL sub-class cholesterol distribution, which was similar to that of normal controls. Plasma apo AI in obese patients was not affected by changes in body weight, and remained below normal. The percentage protein-lipid composition of LDL2 and HDL3 in obese patients was characterized by a decreased cholesterol ester content before gastroplasty which was normalized 12 months after gastroplasty. The presence of IDL and LDL3 in increased concentrations in severely obese patients may represent a vascular risk factor since similar abnormalities were recently observed in non-obese patients affected with vascular diseases.

[Lipolytic and lipoprotein lipase activity of subcutaneous and visceral adipose tissue in Cushing's syndrome]. / Attività lipolitica e lipoproteinlipasica nel tessuto adiposo sottocutaneo e viscerale nella sindrome di Cushing.

Cushing's syndrome has been recently compared to visceral-type obesity, since it is characterised by the accumulation of adipose tissue at a deep abdominal site, to the detriment of the subcutaneous adipose panniculus, and is associated with insulin-resistance and hyperlipemia. The aim of the present study was to evaluate the influence of glucocorticoid hormones on lipolytic activity (index of FFA mobilisation) and on lipoproteinlipase (LPL) activity (an index of the accumulation of triglycerides) in subcutaneous and perirenal adipose tissue in order to clarify the mechanisms involved in this type of accumulation in Cushing's syndrome. Five patients (4 F and 1 M) were included in the study, mean age 27.8 +/- 3.7 years and BMI 21.3 +/- 1.2 kg/m2; patients were hospitalised in the 2nd Surgical Clinic at the University of Padua and underwent surgery for secondary corticosurrenal hyperplasia with ACTH secreting hypophysial adenoma. Lipolytic activity in subcutaneous adipose tissue in these patients was significantly lower (p less than 0.05) than in control subjects, in particular after noradrenalin stimulation (p less than 0.01). No significant difference was observed when lipolytic activity in subcutaneous adipose tissue was compared to that one in perirenal tissue. LPL activity in subcutaneous adipose tissue did not reveal statistically significant differences compared to control subjects, although values were lower. A further decrease in LPL activity, which was not however significant, was observed in perirenal tissue in comparison to subcutaneous tissues in the same patients. The mean weight of adipocytes (ug) was slightly lower in subcutaneous adipose tissue compared to control subjects and even lower in perineal tissue in comparison to the subcutis in the same patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vertical gastroplasty. Evaluation of efficacy]. / La gastroplastica verticale. Valutazione dell'efficacia.

The paper evaluates the results of vertical gastroplasty in the treatment of morbid obesity. A series of 34 patients (24 F and 10 M) with the following characteristics was included in the study: mean age 41 years, preoperative weight 141 kg, % of ideal weight 204%, BMI 49; mean follow-up was 35 months. Postoperative mortality was zero and there were reduced early and long-term complications. Mean weight loss, expressed as a percentage of overweight, at 6 months was 48.5%, 56.8% at 12 months, 63.4% at 24 months and 67.2% at 36 months. The authors conclude that, given the low incidence of complications and the satisfactory weight loss which was maintained long after the operation, vertical gastroplasty appears to be the preferred operation, since it represents a safe and effective method of treating pathological obesity.

Lipid metabolism in lipoatrophic diabetes.

Some aspects of lipid metabolism were studied in 4 patients with a congenital lipoatrophic diabetes (LAD) associated to a type IV hyperlipoproteinemia. The analysis of lipoprotein composition, expressed as mg/dl, demonstrates a significant increase of VLDL mass and a significant reduction of HDL mass. The analysis of lipoprotein composition, expressed as per cent of total mass demonstrates an increase of the triglyceride content in all fractions and a significant reduction of the cholesterol and phospholipid content in HDL2 particles. Apo C-II, C-III0, C-III1 and C-III2 levels in lipoprotein fractions were normal in LAD patients. Lipoprotein lipase activity in omental adipose tissue, collected during laparoscopy in one patient was undetectable. The serum of this patient did not fully activate the lipoprotein lipase eluted from normal adipose tissue. In all patients the adipose tissue lipoprotein lipase activity in post-heparin plasma was blunted or near absent. Thus a reduced peripheral clearance of triglyceride-rich lipoprotein could be an important determinant of lipoprotein abnormalities in lipoatrophic diabetes.

Visceral obesity and diabetes.

The cross-sectional subcutaneous and visceral areas of adipose tissue, measured on computed tomographic scans at abdominal level and the subcutaneous/visceral fat area ratio (S/V ratio) distribution have been calculated in 155 subjects. Using the S/V ratio as discriminator, two groups of patients of both sexes, with subcutaneous or visceral type of obesity have been selected. Metabolic studies demonstrate a significant reduction of glucose tolerance at the oral glucose load and a significant increase of the insulin response in patients with visceral obesity. The size of the omental fat cells was larger in visceral obesity, while the size of subcutaneous fat cells was larger in subcutaneous obesity. A significant correlation was found between the S/V area ratios and the subcutaneous/visceral fat cell weight ratios. In vitro studies on subcutaneous and omental fat obtained during surgery from 9 patients with subcutaneous obesity and 7 patients with visceral obesity demonstrate a significantly higher isoprenaline-stimulated lipolytic response in omental fat of patients with visceral obesity. The lipoprotein lipase activity in subcutaneous fat was higher than in omental fat in both types of obesity.

In vitro effects of glucidamine on adrenergic stimulated lipolysis and on lipoprotein lipase activity in human adipose tissue.

Glucidamine, a purified glycoprotein-mucopolysaccharide complex displays dose-dependent lipolytic effect on human adipose tissue in vitro. On adipose tissue lipoprotein lipase activity glucidamine exhibits an heparin-like effect in eluting the enzyme from the tissue stores to the medium of incubation. No activating effects of glucidamine on lipoprotein lipase eluted from human adipose tissue was observed.

Asymmetrical lipomatosis: report of two cases.

We report on two patients with an asymmetrical expansion of fat tissue. At computed tomography, lipomatous tissue proved to be superficially located in one patient and both subcutaneously and deeply located in the second. Signs and symptoms of a peripheral neuropathy were observed in both patients, who were otherwise asymptomatic. The lipolytic activity in post-heparin plasma was normal in both patients. The fat cell size of lipomatous tissue, obtained in one patient by percutaneous needle biopsy, was higher than that of contralateral, uninvolved adipose tissue. The adipose tissue lipoprotein lipase activity in lipomatous tissue was higher than that in normal tissue. High density lipoprotein (HDL), HDL2 and HDL3 cholesterol values were elevated in both patients but not exceeding 1 standard deviation the values of age and sex matched controls. Isoprenaline-stimulated lipid mobilization was similar in lipomatous and in control tissue.

Lipoprotein metabolism in patients with elevated lipoprotein-lipase activity in adipose tissue.

We have evaluated the relationships between adipose tissue lipoprotein-lipase activity (AT-LPL) or post-heparin plasma lipolytic activity (PHLA) and the composition of circulating lipoproteins in 7 patients with multiple symmetric lipomatosis (MSL). In addition we have investigated the behaviour of serum triglycerides after an oral fat load (1 g triglycerides/kg body weight) in 5 MSL patients and in 5 age and sex matched controls. We found significantly higher values of HDL, HDL2 and HDL3 cholesterol in MSL patients than in controls. Moreover, HDL2/HDL3 cholesterol ratio was higher in MSL patients than in controls, which indicate a predominant increase in HDL2 subfraction. The mean values of AT-LPL in lipomatous tissue was significantly higher than in control tissue. A positive statistically significant correlation was found between AT-LPL activity and HDL, HDL2 and HDL3 cholesterol values. After the fat load the maximal increments of serum triglyceride levels and the triglyceride areas over 8 and 12 h are lower in MSL patients than in controls; there was an inverse, statistically significant correlation between the total PHLA or the extrahepatic PHLA values and the triglyceride areas after lipid load. We conclude that MSL represents a useful naturally occurring model for the study of the role of AT-LPL in the metabolism of triglyceride-rich lipoproteins and in the clearance of lipoproteins in the post-prandial phase.

Mediastino-abdominal lipomatosis: deep accumulation of fat mimicking a respiratory disease and ascites. Clinical aspects and metabolic studies in vitro.

We report on clinical and metabolic studies of a newly delineated lipomatosis, characterised by an abnormal mediastinal and abdominal accumulation of fat, without obesity. The clinical features, which occurred in all the patients studied, are: Exertional dyspnoea due to a space-occupying mediastinal accumulation of fat, without evidence of cardiac or pulmonary disease. A pseudo-ascitic abdominal enlargement, due to intra- and retroperitoneal accumulation of fatty tissue. Insulin-independent diabetes mellitus. Type IV hyperlipidaemia and elevated levels of plasma uric acid were observed in four patients. Intra-abdominal lipomatous tissue, obtained during laparoscopy from four patients, demonstrated a reduced lipolytic response to beta-adrenergic stimulation. Thus, fat deposition in the abdominal and mediastinal areas could be causally related to defective lipid mobilization in lipomatocytes. Lipoprotein lipase activity in abdominal adipose tissue were normal in two patients (10.0 and 10.6 nmol/g/min) and markedly elevated in another two patients (37.3 and 49.9 nmol/g/min), as compared with controls (12.7 +/- 2.1 nmol/g/min). When expressed on per cell basis, LPL activity in lipomatous tissue was significantly higher than in control tissue (3.21 +/- 1.1 nmol/10(5) cell/min vs 0.92 +/- 0.16 nmol/10(5) cell/min). Lipoprotein fractionation did not demonstrate consistent modification of the serum lipoprotein pattern. HDL and HDL2 cholesterol values were reduced, even in patients with elevated LPL activity in adipose tissue.