Liver steatosis

Accumulation of lipids in the liver (steatosis) is one possible mechanism for liver toxicity. Several compounds causing necrosis of hepatocytes also cause steatosis. There are, however, some doubts that steatosis would be the primary cause of liver injury. Several compounds cause steatosis (e.g., puro-mycin, cycloheximide) without causing liver injury. Most of the accumulated lipids are triglycerides. In steatosis, the balance between the synthesis and excretion of these lipids has been disturbed (see Table 5.13). 

High-fat diet studies with DGATl-/- and DGATl+/- mice demonstrated that the absence of DGAT1 activity may lead to increased insulin sensitivity, leptin sensitivity, protection against diet-induced obesity, and protection against liver steatosis [40-43]. 

Abetalipoproteinemia or Bassen-Kornzweig syndrome, a potentially disabling, familial disease characterized by lack of plasma TGs, malabsorption of fat-soluble vitamins, liver steatosis, steatorrhea, and other symptoms, is linked to mutations in the MTP functional subunit [52,53],... 

Chariot, P. et al. (1999) Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. Journal of Hepatology, 30 (1), 156-160. 

Brivet FG, Nion I, Megarbane B, Slama A, Brivet M, Rustin P, Munnich A. Fatal lactic acidosis and liver steatosis associated with didanosine and stavudine treatment a respiratory chain dysfunction J Hepatol 2000 32(2) 364-5. 

Jacqueson A. Thevenin M, Wamet JM, et al. 1978. Comparative study of the protective effect of an anabolic steroid. The 19-nortestosterone-phenylpropionate (19 NTPP) on liver steatosis induced by Amanita phalloides and white phosphorus in rats. Arch Toxicol 1 193-196. 

MODIFICATION OF THE METHOD Hazle et al. (1991) used MRS to follow the time course of ethanol induced liver steatosis in rats. Spectra were acquired without respiratory triggering and lipid signal was normalised to signal from an external reference sample. Correlation between MRS normalised lipid signal and biochemically determined lipids was moderate (r = 0.52). Ling et al. (1992) used respiratory triggered MRS to examine the same model and were able to show that a 5.5-fold increase in lipid signal on... 

Deposits of tiny fat droplets Formation of small fat droplets = small-droplet liver steatosis... 

Tab. 31.2 Formation, localization and various courses of liver steatosis resulting in the development of fatty liver (WW = wet weight of liver)...

Tab. 31.5 Acquired causes of liver steatosis or fatty liver (including some references)...

Tab. 31.7 Liver steatosis or fatty liver due to medication, chemical substances or toxins (s. tab. 29.10 )...

The development of liver steatosis is attributable to various exogenous and endogenous mechanisms, which may combine with and/or potentiate each other, (s. tab. 31.1) Numerous causal factors must be considered in the pathogenesis of fatty liver, (s. tabs. 31.5, 31.7)... 

Inhalation of bromotrichloromethane by rats increased total lipids in liver and stimulated hepatic lipid peroxidation. After intragastric administration, liver steatosis was observed. Rats injected with 0.26 mmol bromotrichloromethane died after massive accumulation of neutral lipids and necrosis of the liver. 

D DIGE MS Compound A Rat liver Chemical liver steatosis study T Acetyl CoA pathway enzymes 4- sulfite oxidase... 

Specific inhibitors of the lipid transfer activity of MTP have been developed as a potential treatment for atherosclerosis based on the premise that inhibition of MTP reduces VLDL secretion. Indeed, MTP inhibitors effectively reduce plasma cholesterol levels by up to 80% in rats, hamsters, and rabbits [13]. However, heterozygosity for MTP deficiency in humans does not diminish plasma lipids or lipoproteins, indicating that a modest reduction in MTP activity does not limit VLDL production. On the other hand, adenovirus-mediated over-expression of MTP in mouse liver increased the secretion, and plasma levels, of TG, apo B100, and apo B48 (D.J. Rader, 1999). MTP inhibitors are not currently used therapeutically, probably because they induce some storage of TG in the liver (steatosis) as a result of the blockage in VLDL secretion. 

Chabrol B, Mancini J, Chretien D, Rustin P, Munnich A, Pinsard N (1994) Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency. Eur J Pediatr 153 133-135 Chariot P, Drogou I, de Lacroix-Szmania I, Ehezer-Vanerot MC, Chazaud B, Lombes A, Schaeffer A, Zafrani ES (2000) Zidovudine-indueed mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. J Hepatol 32 364-365 Chen CH, Cheng YC (1989) Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeflcieney vims compound 2, 3 -dideoxycytidine. J Biol Chem 264 11934-11937... 

The concept of steatosis (fat accumulation in the liver) is a common one for looking at the effect of solvents (those which are known to be toxic to the liver). The fat accumulation is the result of abnormal transport of lipids and as a result, accumulation of lipids in the liver. Therefore clinically industrial exposure to hepatotoxic solvents is associated with liver steatosis, among others. 

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