John B. Somer

Lipoprotein lipids in chronic renal failure and haemodialysis. The influence of etiology and implications for atherogenesis

Lipoprotein lipid analysis has been carried out in 39 women and 28 men with chronic renal failure on haemodialysis. The results have been analysed in relation to the etiology of the renal disease and compared with those obtained in age- and sex-matched controls and in triglyceride-matched controls. Serum cholesterol was normal or low in glomerulonephritis but was normal in analgesic nephropathy. Serum triglycerides and VLDL lipids were raised uniformly regardless of the etiology of the renal disease. LDL triglyceride and HDL triglyceride were also raised. LDL cholesterol and phospholipid were low in glomerulonephritis but were normal in analgesic nephropathy. HDL cholesterol was reduced in both male and female patients regardless of etiology, statistical significance was not reached for the women. The ratio of esterified to free cholesterol tended to be reduced in all the lipoproteins regardless of sex or etiology but the changes were not significant in all groups. Comparison of the lipid abnormalities with those found in other hyperlipidaemic states suggests that the lipid disorders found in chronic renal failure are probably insufficient to explain the rapid development of vascular disease which has been reported.

Serum lipoprotein abnormalities in renal allograft recipients

Detailed lipid composition of serum and isolated lipoprotein fractions in male and female transplant recipients has been determined. Results have been compared with appropriate controls and a number of abnormalities have become apparent: (i) Serum total cholesterol, triglyceride and phospholipid levels were significantly elevated in transplant recipients. (ii) All lipid classes VLDL were significantly increased in both male and female patients. (iii) LDL-total cholesterol, triglyceride and phospholipid were significantly raised in female transplant patients, but this was true only for LDL-triglyceride in male patients. (iv) In female patients, HDL-total cholesterol and -triglyceride were significantly elevated, while in male patients, HDL-total cholesterol, but not HDL-triglyceride, was significantly greater than in controls. (v) The ratio of esterified to free cholesterol was significantly reduced in HDL of female transplant recipients. Results from correlation analysis suggest a relationship between some of the lipid abnormalities and renal function in female patients, while in male patients only immunosuppressive therapy is implicated.

Further studies of the ethanol-induced changes in pancreatic lipid metabolism.

Abstract Previous in vitro studies have shown that ethanol increased de novo triglyceride synthesis in the rat pancreas. The present study extends these observations on the effects of ethanol on pancreatic lipid metabolism. Ethanol significantly stimulated [1- 14 C]acetate incorporation into pancreatic lipids at concentrations as low as 0.068 m M , as well as at 3.4 and 34 m M . This suggests that known metabolic pathways of ethanol oxidation are not involved in these changes. Ethanol also stimulated the incorporation of [1- 14 C]oleate into pancreatic triglyceride and cholesteryl ester, but not into phospholipids. These changes were less marked than those obtained with [1- 14 C]acetate. Furthermore, incorporation of [1- 14 C]palmitate into pancreatic lipid was affected even less by ethanol. Thus, ethanol-induced changes in pancreatic lipid metabolism are unlikely to be due to fatty acid esterification alone.

Chronic ethanol feeding causes accumulation of serum cholesterol in rat pancreas

In a previous study, a rat model of ethanol-induced pancreatic steatosis was developed in which chronic ethanol feeding resulted in a twofold increase in pancreatic cholesteryl ester content. The studies reported here were performed in order to elucidate the mechanism of this cholesteryl ester accumulation. Rats were pair fed ethanol or control diets for 3 weeks. Ethanol feeding resulted in an increased accumulation of serum cholesterol in the pancreas. Ethanol feeding also resulted in increased in vitro incorporation of labeled acetate and mevalonate into the sterol moiety of pancreatic cholesteryl ester and increased incorporation of labeled acetate into its fatty acid component. These results suggest that chronic ethanol feeding causes pancreatic cholesteryl ester accumulation by affecting exchange of cholesterol between serum and pancreatic tissue.

Combined hyperlipidemia and hypertriglyceridemia in renal allograft recipients. Comparison with non-renal combined hyperlipidemic or hypertriglyceridemic patients and normal subjects

In order to investigate the degree of similarity between renal transplant and non-renal combined hyperlipidemic and hypertriglyceridemic patients, serum and lipoprotein lipid compositions were compared in transplant and non-renal combined hyperlipidemic and in transplant and non-renal hypertriglyceridemic patients, and normal subjects. Although certain similarities were demonstrated, combined hyperlipidemia in transplants differed from that in non-renal patients in a number of respects: (1) LDL-triglyceride levels were increased to a greater extent in transplant than in non-renal patients in females, while LDL-phospholipid was elevated in male transplants only; (2) HDL-cholesterol levels were raised in transplants relative to non-renal patients in females, and relative to both non-renal patients and normal subjects in males; (3) a number of differences in lipoprotein-lipid ratios between transplant and non-renal patients were demonstrated for all three lipoprotein fractions. In hypertriglyceridemia, changes in lipoprotein-lipid levels were similar in transplant and non-renal patients with the exception of HDL-cholesterol levels, which were decreased in non-renal patients only. Furthermore, the ratio of esterified to free cholesterol in LDL and HDL was decreased in non-renal but not in transplant patients. The data presented demonstrate that, despite certain similarities, a number of the lipoprotein-lipid changes observed in transplant combined hyperlipidemia and in transplant hypertriglyceridemia differ from those observed in non-renal patients with similarly elevated serum lipids.

Increased denovo phospholipid biosynthesis in the stimulated rat exocrine pancreas

Abstract Sincalide significantly stimulated the incorporation of uniformly labelled 14C-glucose into pancreatic phospholipids, but not into neutral lipids. Incorporation into phosphatidyl inositol was stimulated to the greatest degree followed by phosphatidyl ethanolamine, and phosphatidyl choline and lysophosphatidyl choline. Incorporation of label into the phospholipid glycerol backbone was enhanced suggesting increased de novo phospholipid biosynthesis. It is suggested that in the stimulated exocrine pancreas phospholipid metabolism may be altered in a number of ways.

Hypercholesterolemia in renal allograft recipients Comparison with non-renal hypercholesterolemia and normal subjects☆

In order to investigate the degree of similarity between renal transplant and non-renal hypercholesterolemia, serum and lipoprotein lipid compositions were compared in female transplant hypercholesterolemic patients (serum cholesterol greater than 240 mg/100 ml, serum triglyceride less than 150 mg/100 ml) and female non-renal hypercholesterolemic and normal subjects. A number of lipid abnormalities were demonstrated: (1) Serum and LDL cholesterol and phospholipid levels were significantly elevated in both transplant and non-renal hypercholesterolemic patients; (2) Serum triglyceride, VLDL choelsterol, triglyceride and phospholipid, and LDL and HDL triglyceride were significantly increased in transplant hypercholesterolemic patients. Changes of this nature are usually found in hypertriglyceridemia, and were not observed in non-renal hypercholesterolemic subjects. Finally, a number of changes in the ratio of esterified to free cholesterol and in the ratios of other lipoprotein-lipids, most of which did not correspond to any changes found in the common non-renal hyperlipidemias, were also demonstrated.

The influence of pre-transplant etiology of renal disease on lipoprotein lipids in female renal allograft recipients

Serum and lipoprotein lipids were determined in 42 female transplant recipients and compared with age-matched and serum lipid-matched normal subjects. Eight patients had glomerulonephritis as the pre-transplant etiology of renal disease, 22 had analgesic nephropathy, 6 polycystic kidneys and 6 ureteric reflux. A number of abnormalities were observed: (i) Serum triglycerides and phospholipids were elevated in all patients. Serum cholesterol levels were increased in analgesic nephropathy, polycystic kidney and ureteric reflux, but not in glomerulonephritis patients. The serum esterified/free cholesterol ratio was reduced in all patients except those with polycystic kidneys as the pre-transplant diagnosis; (ii) All VLDL lipids were raised in transplant patients regardless of etiology of renal disease prior to transplantation; (iii) LDL lipids, cholesterol, triglyceride and phospholipid were elevated in analgesic nephropathy, polycystic kidney and ureteric reflux patients, but were normal in glomerulonephritis patients: (iv) HDL cholesterol and triglycerides were elevated in all patients regardless of etiology. HDL phospholipid levels also tended to be raised, but this was significant only in glomerulonephritis patients. Lipoprotein--lipid ratio data indicated that lipoprotein--lipid composition deviated less from normal in glomerulonephritis patients than in the other patient groups.

Lipoprotein lipids in renal transplant recipients of different pre-transplant etiology of renal disease A comparison of male and female patients

Serum and lipoprotein lipids have been compared in male and female transplant recipients with glomerulonephritis or analgesic nephropathy as etiology of pre-transplant renal disease, and a number of differences were observed. (1) Serum cholesterol and phospholipid levels were elevated in glomerulonephritis and female analgesic nephropathy, but not in male analgesic nephropathy patients. (2) Glomerulonephritis patients had normal low density lipoprotein (LDL) cholesterol levels whereas these were elevated in female and depressed in male analgesic nephropathy patients. (3) LDL phospholipid, on the other hand, was normal in male and elevated in female transplant recipients irrespective of etiology of pre-transplant renal disease, while high density lipoprotein (HDL) phospholipid levels were elevated in female glomerulonephritis patients only. Mild hypertriglyceridemia and a tendency to increased HDL cholesterol were observed in all patients. These results provide further evidence for the complexity of lipoprotein lipid abnormalities in renal disease.