The genetic background modifies the effects of the obesity mutation, ‘fatty’, on apolipoprotein gene regulation in rat liver

Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats

“…Using samples from individual rats, an increase of 56% was observed but this was not statistically significant (p=0.083, data not shown). As in earlier experiments [24,25], basal hepatic Apoa4 mRNA abundance was significantly higher in obese Zucker rats compared with lean controls, while Apoc3 mRNA was unchanged (Figs. 1, 3).…”

“…In contrast to Apoa5, basal hepatic Apoa4 mRNA abundance was significantly higher in obese Zucker rats than in lean controls, as in earlier experiments [24,25]. The mechanism of this increase, which is also seen in Wistar fatty rats and in rats made obese by a ventromedial lesion of the hypothalamus, is post-transcriptional and probably occurs at an early step of mRNA maturation [24,25,28].…”

“…In the liver of obese Zucker rats and other rat models of obesity, Apoa4 mRNA is increased [24,25,28,29], whereas Apoc3 mRNA levels are similar in lean and obese Zucker rats [25]. Dose-dependent inhibition of apoA-IV production in rat hepatocyte cultures by insulin has been described [30], suggesting that the overexpression of Apoa4 in the liver of obese rats may be related to insulin resistance.…”

“…These diets reduce hepatic lipogenesis and VLDL synthesis by incompletely understood mechanisms and increase fatty acid oxidation via activation of PPARα (reviewed in [26]). Fish oil diets markedly reduce the transcription of Apoa1 and Apoa4 in rat liver without affecting Apoc3 mRNA abundance [24,25,27]. It is unknown whether the expression of Apoa5 is altered by dietary ω-3 PUFA and whether apoAV may contribute to their triglyceride-lowering effect.…”

“…The resulting improvement in insulin sensitivity is associated with a marked decrease in plasma triglycerides. In addition to pharmacological interventions, the increased plasma triglycerides in obese Zucker rats can be reduced by fish oil diets rich in ω-3 polyunsaturated fatty acids (PUFA) [23][24][25]. These diets reduce hepatic lipogenesis and VLDL synthesis by incompletely understood mechanisms and increase fatty acid oxidation via activation of PPARα (reviewed in [26]).…”