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Mammary expression of activating transcription factor 4 (ATF4) and tribbles homolog 3 (TRB3) is up‐regulated during CLA‐induced inhibition of milk fat synthesis in the dairy cow
Author(s) -
Harvatine Kevin J,
Boisclair Yves R,
Bauman Dale E.
Publication year - 2008
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.22.2_supplement.728
Subject(s) - atf4 , xbp1 , conjugated linoleic acid , unfolded protein response , endocrinology , biology , integrated stress response , fatty acid synthase , medicine , endoplasmic reticulum , chemistry , microbiology and biotechnology , linoleic acid , lipid metabolism , messenger rna , fatty acid , biochemistry , rna splicing , gene , rna , translation (biology)
Trans‐10, cis‐12 conjugated linoleic acid (CLA) originating from ruminal fatty acid biohydrogenation causes milk fat depression (MFD) in dairy cows through a coordinated decrease in mammary expression of lipogenic enzymes. Endoplasmic reticulum (ER) stress is emerging as a causative mechanism of metabolic diseases, with ATF4 and TRB3 providing a link between ER stress and metabolism. TRB3 inhibits AKT1, MAPK, and acetyl‐CoA carboxylase. Our objective was to examine the expression of ATF4 and TRB3 during MFD. ATF4 and TRB3 expression was increased in mammary tissue during MFD induced by a low forage, high oil diet fed for 11 d but not by 3 d infusion of CLA. Temporal response was subsequently investigated. An initial priming dose of 7.5 g of CLA was given followed by infusion of CLA for 5d. TRB3 and ATF4 expression was increased at 12 h but not at 30 h and 5 d. Although TRB3 and ATF4 are associated with ER stress signaling, we did not observe increased expression of the chaperone protein HSPA5 or alternate splicing of XBP1 indicating a non‐classical ER stress response. CLA induces TRB3 and ATF4 expression in some conditions, but the inconsistency of the signaling response calls into question the functional importance of TRB3 and ATF4 in the lipogenic phenotype of classical MFD. [USDA‐NRI 2006‐35206‐16643]