Health aspects of oxidized dietary fats - Oxidation in Foods and Beverages and Antioxidant Applications - page 154

et al., 2005) the rat was used as an animal model. For oral administration of the
ethanol, the Lieber-DeCarli liquid diet was used, which provides an excellent
means for reproducing early lesions of alcoholic liver disease such as steatosis
(Hall et al., 2001). This study clearly demonstrated that triacylglycerol
accumulation in response to ethanol-feeding is markedly reduced in rats by
simultaneous administration of dietary oxidized fat when compared to a fresh
fat. The observation that dietary oxidized fat resulted in similar hepatic
triacylglycerol levels during ethanol-feeding as observed in rats fed fresh fat in
the absence of ethanol suggests that dietary oxidized fat is indeed capable of
preventing alcoholic fatty liver disease.
To elucidate the molecular mechanisms underlying these beneficial effects of
oxidized fat, the transcript levels of PPAR and several genes involved in fatty
acid catabolism, that are known to be reduced by ethanol administration, were
determined in this study (Ringseis et al., 2007b). These investigations showed
that, in agreement with previous studies (Fischer et al., 2003; Crabb et al.,
2004), the transcript levels of PPAR and its target genes were reduced by
ethanol-feeding (Ringseis et al., 2007b). However, administration of the
oxidized fat, but not fresh fat, during ethanol-feeding resulted in the induction
of PPAR target genes involved in fatty acid oxidation, which is indicative of
PPAR activation, even in the presence of ethanol. Based on these results, it has
been concluded that the oxidized fat-induced expression of PPAR target genes
enhanced the capacity of the liver to oxidize fatty acids and, thus, counteracted
the elevated levels of triacylglycerols and the diminished PPAR function
during ethanol-feeding (Ringseis et al., 2007b).
Similar observations as with oxidized fat have been made using synthetic
PPAR agonists such as WY-14,643 and fibrates (Fischer et al., 2003; Tsutsumi
and Takase, 2001; Spritz and Lieber, 1966). Treatment with WY-14,643
restored the ability of the PPAR/RXR complex to bind its specific PPAR
response element and induce transcript levels of many PPAR target genes
resulting in a higher rate of fatty acid -oxidation (Fischer et al., 2003).
Consequently, excessive accumulation of triacylglycerols in the liver during
ethanol-feeding is prevented by these agents (Fischer et al., 2003; Tsutsumi and
Takase, 2001; Spritz and Lieber, 1966). Thus, the results of the study dealing
with oxidized fat (Ringseis et al., 2007b) suggest that dietary oxidized fat
prevents fatty liver development by similar mechanisms as reported for synthetic
PPAR activators.
7.6.3 Effects of oxidized fats on carnitine homeostasis
Many years ago it was shown that starvation or treatment of rats with PPAR
agonist clofibrate increases the concentration of carnitine in the liver (McGarry
et al., 1975; Brass and Hoppel, 1978; Paul and Adibi, 1979). Carnitine is an
essential metabolite, which has a number of indispensable functions in
intermediary metabolism, like the transport of activated long-chain fatty acids
from the cytosol to the mitochondrial matrix where -oxidation takes place