Linoleic acid, an ω‐6 PUFA, has been proposed to inhibit de novo lipogenesis (DNL) by decreasing expression of SREBP‐1c, a major regulator of DNL. To investigate whether previous intake of a high linoleic acid diet inhibits carbohydrate‐stimulated SREBP‐1c expression and DNL in vivo, we compared the expression of SREBP‐1c and its lipogenic targets in the fasted and post‐meal states in male Sprague‐Dawley rats fed: 1) a 55% fat (78% linoleic acid) diet (n=15, P); 2) a 55% fat (linoleic acid‐free) diet (n=15, S); or 3) a no‐fat diet (n=15, N) for 1 wk. All rats were fasted for 24 h; liver samples were obtained at fasting, 16h after refeeding on a 74% carbohydrate, fat‐free meal, or 45 min after injection with insulin + glucose.
 Body weights and liver lipid levels were greater in P and S than N rats (P=S>N; p< .01) but % body fat was higher in P than S rats (P>S=N, p< .01). Refeeding increased mRNA for SREBP‐1c and the lipogenic enzymes Acetyl CoA Carboxylase, Steroyl CoA Desaturase 1, and Pyruvate Kinase compared with fasting in all groups similarly, but expression of Fatty Acid Synthase was lower in the P vs. S group (p< .02). In all groups, refeeding or insulin decreased Phosphoenolpyruvate Carboxykinase mRNA and increased Glucokinase mRNA, indicating normal insulin sensitivity. Refeeding decreased expression of INSIG2, a protein which inhibits maturation of SREBP‐1c, in the S and N groups (p< .002), but not the P group.The minimal reduction in the stimulation of lipogenic gene expression seen in the high‐linoleic acid group was not associated with decreased expression SREBP‐1c, but was associated with lack of suppression of INSIG2 expression, suggesting that ω‐6 PUFA may impair processing rather than expression of SREBP‐1c.
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