The effect of feeding fish oils, vegetable oils and clofibrate on the ketogenesis from long chain fatty acids in hepatocytes

Abstract

Groups of rats were fed diets containing 25% fish oil (FO), 25% soybean oil, 25% partially hydrogenated fish oil (PHFO), 25% partially hydrogenated soybean oil (PHSO), 25% partially hydrogenated coconut oil or 0.3% clofibrate for 3 wk. After the animals were fasted for 24 hr, hepatocytes were isolated and ketogenesis from added palmitate, linoleate cis and trans, arachidonate and docosahexaenoate was measured. Ketogenesis after oil feeding was significantly stimulated (two- to threefold) only in cells from the PHFO- and PHSO-fed rats. The stimulation was most apparent with the long chain unsaturated fatty acids as substrates. These fatty acids were relatively poor ketone body precursors in control hepatocytes. Essential fatty acid deficiency did not seem to be the reason for this stimulation. Clofibrate also stimulated ketogenesis significantly (1.5- to 3-fold). The degree of stimulation increased with chain length and degree of unsaturation of the substrate. The activity of the enzyme 2,4-dienoyl-CoA reductase was also studied in the same groups. Its activity was stimulated about fourfold in the clofibrate-treated rats and to a lesser extent by the PHFO, PHSO and FO diets. The activity showed no correlation with the content of unsaturated fatty acids in the diet or their oxidation in isolated hepatocytes. The 2,4-dienoyl-CoA reductase, therefore, does not seem to be a regulatory enzyme in the metabolism of dietary polyunsaturated fatty acids. It is concluded that an induction of the peroxisomal beta-oxidation system most likely is involved in the reported increases in ketogenesis from very long chain polyunsaturated fatty acids.

Molecular cloning of rat mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase and detection of the corresponding mRNA and of those encoding the remaining enzymes comprising the ketogenic 3-hydroxy-3-methylglutaryl-CoA cycle in central nervous system of suckling rat

“…Significantly, potentially ketogenic polyunsaturated fatty acids (PUFAs) such as linoleic, arachidonic and docosahexaenoic acids [15] exhibit facile transfer across the blood-brain barrier during the suckling period [16,17]. Furthermore recent hybridization studies in situ [18,19] have demonstrated the localization of the peroxisome proliferator-activated receptor α (PPARα), a nuclear transcription factor that is activated by a variety of PUFA ligands [20,21], to certain brain regions.…”

Effects of dietary treatment of rats with eicosapentaenoic acid or docosahexaenoic acid on hepatic lipid metabolism

“…EPA and DHA have been suggested to be poor substrates for the diacylglycerol acyltransferase, hence diminishing the flux of these fatty acids into triacylglycerols [7][8][9] and conversely favouring that into phospholipids. High fat diets have been shown to increase rates of mitochondrial β-oxidation [10] using rat liver mitochondria or isolated rat hepatocytes, in particular with diets containing partially hydrogenated oil [11]. Dietary supplementation with EPA or DHA has, with isolated rat hepatocytes, also been demonstrated to increase cellular β-oxidation [12].…”

Mechanisms for the serum lipid-lowering effect of n-3 fatty acids

“…[23] have reported that dietary fish oil accelerates hepatic ketogenesis. Similar results were also found by Wong et al [24] reporting diminished lipogenesis and increased fatty acid oxidation in perfused livers of fish oil fed rats compared with rats receiving safflower oil.…”