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A feared adverse effect of dyslipidaemia therapy by fibrates is myopathy. We examined the effect of fenofibrate (FF) on protein and amino acid metabolism. Rats received a low (50 mg/kg, LFFD) or high (300 mg/kg, HFFD) dose of FF or vehicle daily by oral gavage. Blood plasma, liver, and soleus and extensor digitorum longus muscles were analysed after 10 days. The FF-treated rats developed hepatomegaly associated with increased hepatic carnitine and ATP and AMP concentrations, decreased protein breakdown, and decreased concentrations of DNA and triglycerides. HFFD increased plasma ALT and AST activities. The weight and protein content of muscles in the HFFD group were lower compared with controls. In muscles of the LFFD group there were increased ATP and decreased AMP concentrations; in the HFFD group AMP was increased. In both FF-treated groups there were increased glycine, phenylalanine, and citrulline and decreased arginine and branched-chain keto acids (BCKA) in blood plasma. After HFFD there were decreased levels of branched-chain amino acids (BCAA; valine, leucine and isoleucine), methionine, and lysine and increased homocysteine. Decreased arginine and increased glycine concentrations were found in both muscles in FF-treated animals; in HFFD-treated animals lysine, methionine, and BCAA were decreased. We conclude that FF exerts protein-anabolic effects on the liver and catabolic effects on muscles. HFFD causes signs of hepatotoxicity, impairs energy and protein balance in muscles, and decreases BCAA, methionine, and lysine. It is suggested that increased glycine and decreased lysine and methionine levels are due to activated carnitine synthesis; decreased BCAA and BCKA levels are due to increased BCAA oxidation., (© 2020 Company of the International Journal of Experimental Pathology (CIJEP).)

We report upon the effects of a cycle of long-term starvation followed by re-feeding on the liver-protein turnover rates and nature of protein growth in the rainbow trout (Oncorhynchus mykiss). We determined the protein-turnover rate and its relationship with the nucleic-acid concentrations in the livers of juvenile trout starved for 70 days and then re-fed for 9 days. During starvation the total hepatic-protein and RNA contents decreased significantly and the absolute protein-synthesis rate (A(S)) also fell, whilst the fractional protein-synthesis rate (K(S)) remained unchanged and the fractional protein-degradation rate (K(D)) increased significantly. Total DNA content, an indicator of hyperplasia, and the protein:DNA ratio, an indicator of hypertrophy, both fell considerably. After re-feeding for 9 days the protein-accumulation rates (K(G), A(G)) rose sharply, as did K(S), A(S), K(D)), protein-synthesis efficiency (K(RNA)) and the protein-synthesis rate/DNA unit (K(DNA)). The total hepatic protein and RNA contents increased but still remained below the control values. The protein:DNA and RNA:DNA ratios increased significantly compared to starved fish. These changes demonstrate the high response capacity of the protein-turnover rates in trout liver upon re-feeding after long-term starvation. Upon re-feeding hypertrophic growth increased considerably whilst hyperplasia remained at starvation levels.

It has been shown that alcohol consumption disrupts liver microtubules, impairs protein secretion and leads to ballooning of the hepatocytes in rats. Ethanol-induced hepatomegaly was accounted for by an increase of the hepatocytes volume. To study whether these changes occur in human alcoholic liver disease, hepatic tubular protein and export protein content were measured in 29 cases of alcoholic liver disease and were compared with those of 37 cases of non-alcoholic liver disease and 5 cases of non-hepatobiliary disease. Hepatic polymerized tubulin was significantly decreased in alcoholic liver disease compared to non-alcoholic liver disease (p less than 0.01), while free tubulin was increased in alcoholic liver disease. Hepatic transferrin (one of the export proteins) content was significantly higher (p less than 0.01) and serum transferrin level was significantly lower (p less than 0.05) in alcoholic liver disease than in non-alcoholic liver disease. These findings indicated that even in humans, chronic alcohol consumption decreased hepatic microtubules by impairing polymerization of tubular protein and increased hepatic export protein content. This decrease in hepatic microtubules by chronic alcohol consumption may play an important role in the development of human alcoholic liver disease.

The hepatomegaly that appears after long-term feeding of ethanol results in accumulation of protein that is quantitatively as important as the increase in lipid. The bulk of protein accumulated in the soluble fraction of the cell. Hepatic albumin and transferrin concentrations increase and colchicine-binding protein decreases, thus suggesting an intrahepatic retention of export proteins.