Biochemical Aspects of Fatty Liver

Fatty infiltration of the liver is a rather common lesion, and may be encountered in many different pathological conditions. Notwithstanding the fact that both morphological and chemical aspects are rather uniform, the pathogenesis may be quite different according to the nature of injury. In order to understand the different mechanisms leading to a fatty liver, one has to bear in mind the basic lines of liver involvement in fat metabolism. The liver receives fat or fat precursors from the blood, and it is able to synthesize fat. It oxidizes fatty acids and releases lipoproteins into the blood. Arrival from outside occurs in two forms: ( I ) as chylomicrons, after a fatty meal; (2) in the form of non-esterified fatty acids released from adipocytes. Increased supply of chylomicrons acts as a cause of fatty liver after feeding on a hyperlipidic diet. Increased supply of non-esterified fatty acids occurs after treatment with cortisol or catecholamines or during stress. Also, treatment with inhibitors of cyclic AMP phosphodiesterase, e.g. caffeine and theophylline, may lead to an increased supply of non-esterified fatty acids and to fatty liver. In all these cases the liver behaves as an ‘innocent bystander’, and its function is not necessarily damaged. The presence of infiltration for a long period of time may, however, produce a secondary atrophy of parenchymal cells. Another cause of functional derangement may be imbalance between the amount of accumulated triglycerides and that of naturally occurring antioxidants; this could provoke a readier involvement of liver cells in peroxidative damage (Ugazio et a/., 1967). Involvement of liver function is the primary cause in several other types of fatty infiltration. Changed liver function may act in one or more of the following ways: ( I ) increased synthesis of fat from non-fat precursors; (2) decreased oxidation in mitochondria; (3) decreased release of lipoproteins into the blood. Increased synthesis from acetyl-CoA is still being considered as one of the possible causes of acute ethanol-induced fatty liver (Scheig & Isselbacher, 1965). It has been shown to occur also in animals fed on a diet deficient in unsaturated fatty acids, but its pathogenetic relevance is doubtful. Some evidence has been given that fatty liver produced by phenobarbital treatment (Young et al., 1971 ; Chalvardjian, 1970; Ugazio, 1971) is also due to increased synthesis of fat. Decreased oxidation takes place first of all as a consequence of decreased O2 supply in several forms of hypoxia. It has been found also after exposure to several poisons