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The authors report a study of 28 cases of hyperlipemia due to alcohol. Clinically, they emphasize the predominance of the male sex, the high incidence of digestive disturbances, weight loss and hepatomegaly and the rarity of cardiovascular involvement. From the biochemical point of view, the majority of cases present an endogenous hyperlipemia of the same type as that induced by carbohydrates. Attention is also drawn to the disturbed glucose balance and the frequent hyperuricemia. Moreover, demonstration of lipid anomalies in the relatives of 11 cases out of 15 suggests a genetic predisposition rather analogous to that in carbohydrate hyperlipemia. Treatment by simple withdrawal of alcohol is always effective, but very unreliably adhered to by these patients.

The influence of Halofenate therapy on insulin and glucagon secretion was examined in the Zucker rat with genetic endogenous hyperlipemia. Coincident with the lipid lowering effects of Halofenate, the net change in the basal bihormonal axis favored glucagon, with the I G molar ratio (Insulin/Glucagon) decreasing from 2.72 ± 0.53 to 0.96 ± 0.20 during treatment with this drug. Following arginine stimulation the I G ratio remained reduced at 0.87 ± 0.13 in Halofenate treated animals, contrasting with the statistically greater ratio of 2.5 ± 0.55 in control animals. The Halofenate induced state of reduced insulin:glucagon was associated with hypolipemia, postarginine hyperglycemia, and hyperketonemia,—three metabolic parameters characteristic of glucagon excess relative to insulin. It is suggested that the lipid-lowering action of Halofenate in genetic hyperlipemia may reflect the altered bihormonal axis induced by the drug.

The reversible endogenous hyperlipemia in dogs, elicited by the detergent Triton which was given intravenously, was used to study the interrelations of serum lipids. In the cholesterol ester fraction an increase occurs in both monounsaturated and in saturated fatty acids, excepting myristic; while a decrease occurs in polyunsaturated fatty acids. The fatty acids of cholesterol esters of normal dogs contain 22% oleic acid, and only 24% when serum lipids are increased to almost double their normal value (TC=400-500 mg/100 ml). However there is a critical level above which a rapid rise in oleic acid occurs and, in severe hyperlipemia (TC=1500 +/-430 mg/100 ml), this acid constitutes almost half of the esterified fatty acid component.Since there is no evidence that Triton directly regulates fatty acid synthesis, the lipid fraction-fatty acid interrelationship may be secondary to lipid mobilization from endogenous sources. This concept is supported by the fact that the increased serum fatty acids are only those which can be synthesized by animals. It is suggested, on the basis of a marked increased of endogenously produced fatty acids, that, at critical lipid levels, shortage of polyunsaturated fatty acids from exogenous sources occurs. This might be of sufficient degree to accelerate fatty acid synthesis to meet the need for fatty acids for energy requirements. There may also be need of fatty acid for esterification of chiefly the accumulated free cholesterol split from lipoprotein by Triton.Triton-induced changes in cholesterol ester fatty acids result in patterns which closely resemble those in the adipose tissue of dog and man and in the serum of human endogenous hyperlipemia.

An immunoassay was developed for determining the concentration of the protein moiety of the low-density lipoproteins of human plasma. The concentration of this protein in the plasma was variable; it was higher than normal on the average in patients with familial hyperbetalipoproteinemia (type II) and endogenous hyperlipemia (type IV) and lower than normal in patients with fat-induced (type I) and mixed (type V) hyperlipemia. Patients with endogenous hyperlipemia were separable by the immunoassay into those with normal and those with supernormal low-density lipoprotein protein concentration.