Treatment of normolipidemic rats by alkylthiopropionic
acid (
CETTD), resulted in a dose- and time-dependent increase in total
dihydroxyacetone phosphate acyltransferase (DHAPAT) activity, in extent comparable to that of
3-thiadicarboxylic acid (
BCMTD) and alkylthioacetic
acid (CMTTD). Thus, in
CETTD- and CMTTD-treated rats, the specific DHAPAT activity increased in the microsomal, peroxisomal and mitochondrial fractions. In contrast, repeated administration of the peroxisome proliferator,
BCMTD, decreased the specific DHAPAT activity both in the peroxisomal fraction and in purified peroxisomes. A three-fold increase in specific activity was, however, revealed in the mitochondrial fraction. Whether the variation of the DHAPAT activity in the mitochondrial and microsomal fractions among the feeding groups can be explained by increased number of enlarged and small peroxisomes sedimenting in the fractions, are to be considered. Subcellular fractionation studies confirmed previous findings that rat liver
glycerophosphate acyltransferase (GPAT) was located both in mitochondria and the microsomal fraction.
BCMTD was considerably more potent than CMTTD in stimulating the microsomal and mitochondrial GPAT activities. Administration of
CETTD marginally affected the
isoenzymes of GPAT.
Diacylglycerol acyltransferase (DGAT) activity was increased by 35% in
BCMTD and CMTTD treated rats, but by administration of
CETTD the
enzyme activity was decreased by more than 80%. The
acyl-CoA cholesterol acyltransferase (ACAT) activity was marginally affected in animals treated with
BCMTD, CMTTD and
CETTD. Thus, the results indicate that the initial steps in the synthesis of
triacylglycerols and
ether glycerolipids as well as the last step in
triacylglycerol synthesis could not be identified as mediating the fat accumulation or the lowering of
triacylglycerol content in liver of
CETTD, or
BCMTD and CMTTD treated rats. On the other hand, CMTTD increased the
palmitoyl-CoA oxidation in mitochondria, and
CETTD considerably inhibited the activity. Therefore, it is conceivable that the development of
fatty liver with
CETTD is mostly due to inhibition of mitochondrial beta-oxidation.