The liver, the principal lipogenic organ, is responsible for the conversion of excess dietary carbohydrates to triglycerides. A high carbohydrate diet induces the synthesis of several lipogenic and glycolytic enzymes including acetyl-CoA carboxylase (ACC), 1 fatty acid synthase (FAS), stearoyl-CoA desaturase, ATP citrate lyase, malic enzyme, glucose-6-phosphate dehydrogenase, and pyruvate kinase (PK) (1-3). This coordinate induction of enzymes is due to increased mRNA levels, resulting primarily from the accelerated transcription.Dietary polyunsaturated fatty acids (PUFA) have been well established as negative regulators of hepatic lipogenesis. Allmann and Gibson (4) discovered that adding 2% linoleate to a high carbohydrate fat-free diet suppressed the rate of hepatic fatty acid biosynthesis and the activities of FAS and glucose-6-phosphate dehydrogenase by nearly 70% in mice. In contrast, supplementing the high carbohydrate diet with palmitate, oleate, or cholesterol had no effect on hepatic lipogenesis or the activity of lipogenic enzymes. Since then, several investigators have demonstrated that dietary PUFA of the n-6 and n-3 families suppress hepatic lipogenesis. This anti-lipogenic action of PUFA reflects decreases in mRNA levels of hepatic enzymes including ACC, FAS, stearoyl-CoA desaturase, ATP citrate lyase, malic enzyme, glucose-6-phosphate dehydrogenase, and PK. The regulation by PUFA has been shown to be primarily at the transcriptional level; however, the precise mechanism for this action remains unknown (5-7).Sterol regulatory element-binding proteins (SREBPs) are transcription factors that belong to the basic helix-loop-helixleucine zipper family and regulate enzymes responsible for the synthesis of cholesterol, fatty acids, and triglycerides (8). Unlike other members of the basic helix-loop-helix-leucine zipper family, SREBPs are synthesized as precursors bound to the endoplasmic reticulum and nuclear envelope. Upon activation, SREBPs are released from the membrane into the nucleus as a mature protein by a sequential two-step cleavage process. To date, three SREBP isoforms, SREBP-1a, -1c and -2, have been identified and characterized. The predominant SREBP-1 isoform in the liver is SREBP-1c. Whereas SREBP-2 is relatively selective in transcriptionally activating cholesterol biosynthetic genes, SREBP-1c has a greater role in regulating fatty acid synthesis than cholesterol synthesis in the liver (9 -11, 30).The role of SREBP-1 for the regulation of hepatic lipogenesis has been recently established. Changes in hepatic mature SREBP-1c protein levels were shown to parallel those of mRNAs for lipogenic genes in the liver using a dietary manipulation and a transgenic technology (12). Moreover, SREBP-1 has been demonstrated to be crucial for the carbohydrate stimulation of lipogenic genes in mice with a targeted disruption of SREBP-1 (30).