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Dietary regulation of hepatic and extra‐hepatic lipid metabolism in the liver specific NADPH‐cytochrome P450 reductase knockout model
Author(s) -
Sealls Whitney,
Ding Xinxin,
Black Paul N,
DiRusso Concetta
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a82-d
Subject(s) - polyunsaturated fatty acid , endocrinology , biology , medicine , fatty liver , cytochrome p450 , lipid metabolism , metabolism , fatty acid , biochemistry , fatty acid metabolism , fatty acid desaturase , disease
Metabolic equilibrium is maintained through an integrated network of complex regulatory pathways in mammals. When this metabolic balance is disturbed, serious complications may ensue which can lead to disease states such as metabolic syndrome, obesity, and cardiovascular disease. The polyunsaturated fatty acids (PUFAs) C18:2n‐6 and C18:3n‐3 are taken in from the diet and further processed primarily in the liver to make the highly unsaturated fatty acids (HUFAs) C20:4n‐6, C20:5n‐3, and C22:6n‐3. Liver specific NADPH‐cytochrome P450 reductase (liver‐CPR) null mice show altered liver fatty acid profiles with subsequent alterations in fatty acid gene expression profiles. These mice significantly accumulate saturated and monounsaturated fatty acids, triglycerides, and PUFAs but show diminished ability to synthesize cholesterol and HUFAs. Liver‐CPR null mice show changes in gene expression profiles that correlate with changes in liver fatty acid profiles. It is hypothesized that liver metabolite pools determine patterns of lipid metabolism in both hepatic and extra‐hepatic tissues through transcriptional mechanisms. In the present study, control and liver‐CPR null mice were fed defined diets containing lard, canola oil, menhaden fish oil, and a control standard laboratory diet. This resulted in altered patterns of fatty acid utilization and storage in the liver as well as variable gene transcription.