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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
Author(s) -
Foote Monica R.,
Monks Jenifer,
Harvatine Kevin J.,
Neville Margaret C.,
Boisclair Yves R.,
Bauman Dale E.
Publication year - 2009
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.23.1_supplement.109.7
Subject(s) - sterol regulatory element binding protein , conjugated linoleic acid , fatty acid synthesis , mammary gland , de novo synthesis , medicine , biology , endocrinology , linoleic acid , lactation , chemistry , fatty acid , biochemistry , microbiology and biotechnology , sterol , cholesterol , enzyme , cancer , breast cancer , pregnancy , genetics
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