Date of Graduation
School of Medicine
Microbiology, Immunology, and Cell Biology
Primary hepatocytes treated with non-esterified polyunsaturated fatty acids have been used as a model for describing the inhibitory effects of dietary polyunsaturated fats on lipogenic gene expression. This model resembles starvation or uncontrolled diabetes but not dietary fat ingestion, which is delivered to liver via chylomicron remnants. Chylomicron remnants enriched with polyunsaturated fatty acids stimulate a unique pattern of intracellular signaling. These remnants enhance p38 mitogen activated protein kinase (MAPK) activity but do not inhibit insulin signaling or induce extracellular-signal related kinase (ERK) or AMP-activated protein kinase (AMPK) activation as do non-esterified polyunsaturated fatty acids. Polyunsaturated fatty acids-enriched remnants and non-esterified polyunsaturated fatty acids both inhibit the rate of fatty acid synthesis and the expression of the lipogenic genes, particularly those regulated by sterol response element binding protein-1c (SREBP-1c). Saturated fatty acid-enriched remnants fail to inhibit the lipogenic genes indicating that the inhibitory action of dietary polyunsaturated fats involves regulatory mechanisms in liver. In contrast, polyunsaturated fatty acids-enriched remnants fail to inhibit malic enzyme, glucokinase, L-pyruvate kinase, and cytochrome P450-7alpha (Cyp-7alpha) expression despite their inhibition by non-esterified fatty acids. These genes are regulated independently of SREBP-1c. Therefore, non-esterified polyunsaturated fatty acids do not accurately model all aspects of regulation of hepatic metabolism by dietary fat.
Kohan, Alison Bloom, "Mechanism by which dietary polyunsaturated fat regulates lipogenic gene expression" (2009). Graduate Theses, Dissertations, and Problem Reports. 2889.