Abstract
Milk fat synthesis of ruminants can be inhibited by intermediates of ruminal fatty acid biohydrogenation including trans‐10, cis‐12 conjugated linoleic acid (CLA). These biohydrogenation intermediates signal a coordinated downregulation of genes involved in mammary FA synthesis, transport, and esterification. We have previously reported decreased mammary expression of sterol response element‐binding protein 1 (SREBP1), SREBP1‐activating proteins, and thyroid hormone‐responsive spot 14 (S14) in the cow during diet‐induced milk fat depression (MFD), and treatment with trans‐10, cis‐12 CLA. Liver x receptors (LXR) and retinoid x receptors (RXR) regulate lipogenesis and are known to bind polyunsaturated FA and LXR agonist increases lipid synthesis in mammary epithelial cell culture. The current studies investigated if biohydrogenation products of rumen origin inhibit mammary lipogenesis through LXR and/or RXR. Expression of LXRs was not different in lactating compared to nonlactating bovine mammary tissue, and expression of LXRs, RXRα, and selected LXR and RXR target genes was not changed in mammary tissue during diet‐induced or CLA‐induced MFD in the cow. In bovine mammary epithelial cell culture, LXR agonist stimulated lipogenesis and expression of LXRß, ATP‐binding cassette 1 (ABCA1), SREBP1c, and S14, but LXR activation did not overcome CLA inhibition of lipogenesis and downregulation of LXRß, SREBP1c, and S14 expression. Lastly, expression of the LXR‐regulated carbohydrate‐responsive element‐binding protein (ChREBP) was higher in lactating than nonlactating tissue and was decreased during CLA‐induced MFD. We conclude that changes in mammary LXR expression in dairy cows are not involved in MFD and that trans‐10, cis‐12 CLA inhibition of lipogenesis and diet‐induced MFD appears independent of direct LXR signaling.
Highlights
Mammalian milk fat concentration and composition are variable and responsive to nutritional factors
A comparison of tissues from lactating cows indicated that LXRa and carbohydrate-responsive element-binding protein (ChREBP) were predominantly expressed in liver, and LXRß was ubiquitously expressed at similar concentrations in all tissues except lung (Fig. 2A–C)
We determined if Liver x receptors (LXR), retinoid x receptors (RXR), and ChREBP expression was modified in the mammary gland during nutritional inhibition of milk fat synthesis in the cow
Summary
Mammalian milk fat concentration and composition are variable and responsive to nutritional factors. During diet-induced MFD in the cow, milk fat synthesis is reduced while yields of milk and other milk components are unchanged. The causative factors of MFD are specific fatty acid (FA) intermediates produced during altered ruminal biohydrogenation and trans-10, cis-12 conjugated linoleic acid (CLA) was the a 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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