Urinary concentration of corticoids in ponies with hyperlipoproteinaemia or hyperadrenocorticism.

The urinary corticoid:creatinine (c:c) ratio was determined in ten pony mares suffering from hyperlipoproteinaemia. The mean (+/- sd) urinary c:c ratio of these ten ponies (47 +/- 31 x 10(-6)) was not significantly different from that of twelve pony mares with a pituitary pars intermedia adenoma (31 +/- 18 x 10(-6). The correlation between the urinary concentration of corticoids and plasma total lipids, and the correlation between the urinary c:c ratio and plasma total lipids in ponies with hyperlipoproteinaemia were not significant (P > 0.05; r = 0.53 and r = 0.008, respectively). Preliminary results favour primary hyperadrenocorticism being associated with hyperlipoproteinaemia. In conclusion, the data presented here suggest that cortisol can contribute to insulin resistance in ponies with hyperlipoproteinaemia.

Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.).

Diet-induced hyperlipidaemia in baboons is similar to that in humans. As in humans, the ratio between low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol is a major determinant of atherosclerosis. Baboons, like humans and other non-human primates, vary in their lipaemic responses to dietary lipids. By selective breeding based on variability in plasma and lipoprotein cholesterol response to diet, lines of baboons with high and low responses of various lipoproteins have been developed. Genetic analyses suggest that lipoprotein patterns in response to dietary cholesterol and fat are heritable. Metabolic and molecular studies of high and low LDL and HDL cholesterol responses to dietary lipids have suggested that different mechanisms regulate plasma LDL cholesterol on the chow and on the high cholesterol-high fat (HCHF) diet. On the chow diet, plasma LDL cholesterol levels are positively associated with cholesterol absorption and negatively associated with hepatic LDL receptor levels and, thus, cholesterol absorption and LDL receptors seem to regulate plasma LDL cholesterol levels. However, when the animals consume a human-like fat- and cholesterol-enriched diet, plasma LDL cholesterol levels are not associated with either cholesterol absorption or hepatic LDL receptor mRNA levels, but are negatively associated with plasma 27-hydroxycholesterol concentrations, hepatic sterol 27-hydroxylase activity, and mRNA levels. Hepatic sterol 27-hydroxylase activity and mRNA levels are induced by dietary cholesterol and fat in low responding baboons more than in high responding baboons. Thus, the ability to induce sterol 27-hydroxylase determines the LDL cholesterol response in baboons. High HDL response baboons often have high levels of HDL1 in their plasma. Our studies suggest that the N-terminal fragment of apo C-I with 38 amino acids and a molecular weight of approximately 4 kDa acts as a cholesteryl ester transfer inhibitor peptide in high HDL1 baboons. The inhibitor peptide associates with apo A-1 in HDL to produce a modified apo A-1 protein with a molecular weight of approximately 31 kDa. The inhibitor peptide is a gene product and the presence of this peptide produces an antiatherogenic high HDL1 phenotype.

Hyperlipoproteinaemia associated with atherosclerosis and cutaneous xanthomatosis in a cat.

Bilateral uveitis and multiple xanthomas (fat deposits in the skin) are described in a 3.5-year-old ovariohysterectomized female Persian cat. The cat had been treated for 2 years with corticosteroids. Examinations included a routine blood chemistry profile, radiographic examination of the thorax and abdomen, histopathological examination of multiple skin punch biopsies, and analysis of blood lipid components by cellulose-acetate electrophoresis and by preparative ultracentrifugation studies. Total lipid values were 23 g/l. Ultracentrifugation studies indicated strongly elevated VLDL and LDL fractions and a decreased concentration of the HDL fraction. Because of sudden blindness the cat was euthanized at the request of the owner. Autopsy revealed massive atherosclerotic changes in the large abdominal vessels, the wall of the aorta, and the coronary vessels. Although the exact pathogenesis remains uncertain, these unusual findings might be explained by a primary hyperlipoproteinaemia, complicated by long-term use of corticosteroids.

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

The pathology of an inherited hyperlipoproteinaemia of cats.

The gross and histological features of congenital lipoprotein lipase deficiency are described in eight cats. The main histological features could be directly related to the presence of the chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques. Focal degenerative changes were, however, present within arteries and this may indicate blood vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.

The ultrastructural pathology of five lipoprotein lipase-deficient cats.

The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all stages of development of ceroid were observed. Chylomicron emboli were seen within the glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and thickening of basement membranes of glomeruli, Bowman's capsule and some proximal convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a non-specific reaction of the kidney to noxious insults such as hypoxia caused by emboli. Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane of the lymphocytes were noted, the significance of which is unknown.

Peripheral neuropathy in cats with inherited primary hyperchylomicronaemia.

Primary hyperlipoproteinaemia (hyperchylomicronaemia) with a slight increase in very low density lipoprotein) is described in 20 cats. Fasting hyperlipaemia, lipaemia retinalis and peripheral neuropathies were the most frequently detected clinical signs. The disease is thought to be inherited as an autosomal recessive trait but the exact mode of inheritance has not been determined. Affected cats showed reduced lipoprotein lipase activity measured after heparin activation compared with the response in normal cats. Plasma triglyceride and cholesterol were increased in all the cats with the major proportion of triglyceride and cholesterol being present in chylomicrons. The peripheral nerve lesions were caused by compression of nerves by lipid granulomata. It is probable that the lipid granulomata result from trauma because the nerves most often affected were at sites like the spinal foraminae where they were susceptible to trauma.

Occurrence of idiopathic, familial hyperchylomicronaemia in a cat.

Primary hyperlipoproteinaemia (hyperchylomicronaemia with slight very low density lipoprotein elevation) is described in two related male cats. Fasting hyperlipaemia, lipaemia retinalis and subcutaneous xanthomas were detected on clinical examination. In one cat lipoprotein lipase activity measured after heparin activation was significantly reduced compared to the response in a normal cat. The lipid and protein concentration in each of the lipoprotein classes and the lipoprotein distribution of the two hyperlipaemic cats, two normolipaemic relations and 16 normolipaemic adult cats were determined. Plasma cholesterol and triglyceride levels were elevated in the hyperlipaemic cats with the major proportion of triglyceride and cholesterol being present in chylomicrons whereas in normolipaemic cats the majority of triglyceride was contained in very low density lipoprotein. High density lipoprotein was the predominant lipid carrier in both the normolipaemic and the hyperlipaemic cats but the protein content in chylomicrons was elevated in the two affected cats. The lipoprotein distribution in normal cats in this study agrees with previously reported values. The hyperlipaemic cats showed many of the features of familial lipoprotein lipase deficiency (type I hyperlipoproteinaemia, exogenous chylomicronaemia) which is an inherited disease in man.