An intact SREBP1 pathway is essential for the t ‐10, c ‐12 CLA‐induced inhibition of de novo fatty acid synthesis in the murine lactating mammary gland

Trans ‐10, cis ‐12 conjugated linoleic acid (CLA) is a potent inhibitor of de novo fatty acid (FA) synthesis in the lactating mammary gland. Inhibition of FA synthesis is accompanied by a coordinated decrease in the expression of key mammary lipogenic genes, including sterol response element binding protein 1 (SREBP1). The functional role of the SREBP1 pathway in CLA‐induced inhibition of milk fat synthesis is unknown. Mice expressing a floxed version of the escort protein SCAP, necessary to activate SREBP pathways, were crossed with mice overexpressing Cre under the mammary specific β‐lactoglobulin promoter. Lactating Cre‐ SCAP fl/fl mice and Cre+ SCAP fl/fl mice were orally dosed with water (n = 8) or with 20 mg of CLA (n = 8) for four days. Litters from Cre+ dams showed decreased growth relative to Cre‐ dams. Analysis of milk composition showed that de novo FA synthesis (C<16:0) was decreased in Cre+ mice. CLA decreased growth of litters from Cre‐ mice but had no effect in Cre+ mice. CLA decreased the proportion of C<16:0 in milk of Cre‐ dams but not in Cre+ dams. In addition, CLA decreased the mammary expression of key lipogenic genes (e.g., SCD1, SREBP1c) in Cre‐ dams but not in Cre+ dams. These results demonstrate that an intact SREBP1 pathway is essential for the t ‐10, c ‐12 CLA‐induced inhibition of de novo FA synthesis in the mammary gland. Research supported by NRI, USDA grant #2006‐35206‐16643, and by NIH grant #PO1‐HD38129