Dietary fatty acids modulate hormone repsonses in lactating cows: Mechanistic role for 5′-deiodinase activity in tissue

Supplemental dietary fat provides excess fatty acids (FA), which can alter circulating concentrations of several hormones. To test the effects of fatty acid isomer type and possible sites of regulation, we abomasally infused fat mixtures high in cis-C_18:1 FA (iTRS) or no infusion (NI) and performed intravenous arginine (ARG) and intramuscular thyrotropin-releasing hormone (TRH) challenges. The experimental design was a replicated 3 × 3 Latin square. Challenges were conducted on Days 10 (ARG) and 12 (TRH) after initiation of fat infusion on each of three 4-wk experimental periods. Plasma concentrations of IGF-I were lower (P < 0.01) when cows received iCIS or iTRS compared with NI. Plasma insulin concentrations increased with ARG but responses were not affected by FA. Plasma growth hormone (GH) was unchanged after ARG. Peak plasma GH and thyroid-stimulating hormone (TSH) responses to TRH were blunted (P < 0.05 and P < 0.1, respectively), whereas thyroxine (T₄) and triiodothyronine (T3) responses were augmented post-TRH (P < 0.01) when cows received either FA isomer. Prolactin responses to TRH were not different between infusion treatments, although basal plasma concentrations before TRH were higher in cows infused with iTRS (P < 0.05). To focus on fat regulation of the thyroid axis, we tested directly in vitro the ability of fatty acids dissolved with sodium taurocholate to affect Type-I 5'-deiodinase (5'D) activity in bovine liver homogenates. Homogenate 5'D was not affected by C_2:0---C10:0 fatty acids, but decreased linearly (P < 0.01) with increasing concentrations of C_12:0---C_16:0 and C_18:1 isomers. CisC_18:1 decreased 5′D more than the trans-isomer (P < 0.01), the difference was only apparent at concentrations greater than 0.25 mM. The data suggest that various aspects of pituitary hormone regulation are differentially affected by FA composition. Fatty acid infusion may accentuate end organ responses in the thyroid axis and decrease IGF-I in the somatotropic axis. The data also suggest that FA isomer may alter patterns of extrathyroidal generation of thyroid hormones via direct influences on 5′D.