Dietary fish oil and cytochrome P‐450 monooxygenase activity in rat liver and kidney

Abstract

Lauric acid hydroxylation and aminopyrine N-demethylation were studied in kidney and liver microsomes from rats treated with fish oil. Different doses of fish oil containing 20% eicosapentaenoic acid and 10% docosahexaenoic acid were provided daily to the rats for seven days. In all the groups studied, the lauric acid metabolism was higher in kidney microsomes and the aminopyrine metabolism in the liver microsomes. Although no effect on the renal cytochrome P-450 concentration was detectable, all four fish oil doses increased the hepatic concentration of cytochrome P-450 by a mean 27%. The higher fish oil doses used increased the renal and hepatic microsomal metabolism of aminopyrine. The lauric acid metabolism was increased by fish oil only in the liver. Fish oil, a known inducer of fatty acid peroxisomal beta-oxidation, also induced microsomal activity. These results show that liver and kidney respond in different ways to dietary factors such as fish oil. In addition, our study would suggest that fish oil increased the activity of two different families of liver cytochrome P-450. The activity of kidney lauric acid 11- and 12-hydroxylation, however, was not modulated by fish oil.

Regulation of Gene Expression by Dietary Fat

“…Monooxygenases are microsomal cytochrome P450 (CYP)-linked enzymes that are members of a large enzyme superfamily that catalyzes the oxidation of a diverse array of lipophilic compounds, including hormones, fatty acids, drugs, and xenobiotics (34,104,134). Tissue, gender, age, hormones, and diet affect the abundance of these enzymes.…”

Polyunsaturated Fatty Acid Suppression of Hepatic Fatty Acid Synthase and S14 Gene Expression Does Not Require Peroxisome Proliferator-activated Receptor α

“…However, the in vitro model used in this work may lack factors present in the in vivo system. In summary, PUFA induce peroxisomal and microsomal fatty acid oxidation and suppress de novo lipogenesis (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). This apparent coordinate regulation of lipid metabolism does not involve PPAR␣ as a common mediator.…”

“…1 in particular highly unsaturated n-3 fatty acids, suppress hepatic lipogenesis and triglyceride synthesis/secretion while inducing peroxisomal and microsomal fatty acid oxidation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). These effects on lipid metabolism are due to changes in gene expression leading to induction or suppression of mRNAs encoding key metabolic enzymes (4,(13)(14)(15)(16)(17)(18)(19).…”

Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women

“…Fish oil influenced the activity of hepatic CYP450 (Valdes et al, 1995;Chen et al, 2003), which might consequently influence the metabolism of estrogen. The lower status of n-3 long-chain fatty acids in vegetarians seems to be a good model to investigate the influence of DHA supplementation on estrogen metabolism.…”

“…The oxidative metabolism of estrogen is catalyzed predominantly by hepatic cytochrome P450 (CYP450) (Huang et al, 1998;Yamazaki et al, 1998). Dietary fish oil increased the concentration of hepatic overall CYP450 and some subtypes of CYP450 in rats (Valdes et al, 1995;Chen et al, 2003). A preliminary study of Osborne et al (1998) indicated a decreased extent of 16a-hydroxylation of estradiol in women after supplemented with n-3 fatty acids.…”