Travers M T, Vernon R G, Barber M C
Hannah Research Institute, Ayr, UK.
J Mol Endocrinol. 1997 Oct;19(2):99-107. doi: 10.1677/jme.0.0190099.
We have investigated the mechanisms whereby lipogenesis is markedly suppressed in adipose tissue depots of lactating sheep. Expression of the gene encoding acetyl-CoA carboxylase (ACC), the flux-determining enzyme of the lipogenic pathway, is reduced approximately threefold in both omental and subcutaneous adipose tissue depots during late pregnancy and remains so into lactation when compared with non-pregnant, non-lactating animals. By comparison, total ACC enzyme activity in these adipose depots is suppressed approximately 25- to 30-fold in lactation. Culture of explants from the subcutaneous depot of lactating sheep with insulin plus dexamethasone for 72 h resulted in an approximately sevenfold increase in ACC mRNA, a fivefold increase in total enzyme activity and a marked increase in the proportion of the enzyme in the active state when compared with explants cultured with no added hormones for the same period. However, there was a lag of between 32 and 48 h before marked induction of any of these parameters by insulin plus dexamethasone was observed. Induction of the alpha-tubulin gene paralleled that of the ACC gene, suggesting that cytoskeletal rearrangements are associated with the aquisition of sensitivity to insulin plus dexamethasone. These results demonstrate that the reduction in lipogenic capacity in ovine adipose tissue during lactation is related to repression of the ACC gene, both at the level of steady-state mRNA abundance and possibly at translation, as well as to suppression of the mechanisms that regulate the proportion of ACC in the active state, and these are further related to the marked insensitivity of these parameters to insulin plus dexamethasone in vitro.
我们研究了泌乳母羊脂肪组织库中脂肪生成受到显著抑制的机制。在妊娠后期，网膜和皮下脂肪组织库中编码乙酰辅酶A羧化酶（ACC）的基因表达减少了约三倍，该酶是脂肪生成途径中的通量决定酶，与未怀孕、未泌乳的动物相比，这种减少在泌乳期仍持续存在。相比之下，这些脂肪库中的总ACC酶活性在泌乳期被抑制了约25至30倍。将泌乳母羊皮下脂肪库的外植体与胰岛素加地塞米松一起培养72小时，与同期未添加激素培养的外植体相比，ACC mRNA增加了约七倍，总酶活性增加了五倍，且处于活性状态的酶比例显著增加。然而，在观察到胰岛素加地塞米松对这些参数有明显诱导作用之前，有32至48小时的延迟。α-微管蛋白基因的诱导与ACC基因的诱导平行，表明细胞骨架重排与对胰岛素加地塞米松敏感性的获得有关。这些结果表明，泌乳期间绵羊脂肪组织中脂肪生成能力的降低与ACC基因的抑制有关，这在稳态mRNA丰度水平以及可能在翻译水平上均有体现，同时也与调节ACC处于活性状态比例的机制受到抑制有关，并且这些进一步与这些参数在体外对胰岛素加地塞米松的显著不敏感性有关。
