Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats
Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats
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DOI：
10.3109/13697137.2011.637650
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发表时间：
2012-12-01
期刊：
影响因子：
2.8
通讯作者：
Lavoie, J-M.
中科院分区：
文献类型：
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作者：
Cote, I.;Yasari, S.;Lavoie, J-M.
目的建立大鼠腹腔内脂肪堆积模型（OVX-P和OVX-R），并探讨其与分子生物学标志物的关系。在第一个实验中，卵巢切除大鼠分为三个三分位数的基础上腹内脂肪组织质量。为了加强OVX-P/OVX-R模型，我们进行了第二个实验，其中每组大鼠的数量增加，并测量了不同的分子标记物。在6-8周的时间结束时，卵巢切除大鼠显示下腹部脂肪堆积（下三分位）标记为OVX-R和那些在上三分位为OVX-P。结果OVX-R大鼠显示类似的腹部脂肪增加Sham大鼠，而OVX-P大鼠描绘的腹部脂肪量的两倍高的Sham和OVX-R大鼠。尽管腹部肥胖存在差异，但与Sham大鼠相比，Ovx-R和Ovx-P大鼠的肝脏脂肪含量均高出50%（p < 0.01）。此外，OVX-R和OVX-P大鼠均表现出较高的HOMA-IR评分，（p < 0.05）和更低（p < 0.01）瘦素受体-b和-e、微粒体转移蛋白（MTP）的肝基因表达，和二酰基甘油酰基转移酶-2（DGAT-2）的表达。诱导的肝脂肪变性和相关的胰岛素抵抗可能与腹部脂肪堆积无关，并提示通过瘦素受体下调导致的瘦素作用的降低和通过瘦素受体下调导致的极低密度脂蛋白产生的降低，MTP和DGAT-2的调节可能是在没有外周脂肪增加的情况下导致该观察结果的因素。
Objective The purpose of the present study was to establish a model of rats prone and resistant to intraabdominal fat accumulation in response to ovariectomy (Ovx-P and Ovx-R) and to determine its relationship with molecular biomarkers.Design Two experiments were conducted in which female rats were either sham-operated (Sham) or ovariectomized (Ovx). In the first experiment, ovariectomized rats were stratified into three tertiles based on intra-abdominal adipose tissue mass. To strengthen the Ovx-P/Ovx-R model, we conducted a second experiment in which the numbers of rats in each group were extended and in which different molecular markers were measured. At the end of a 6-8-week period, ovariectomized rats that displayed the lower abdominal fat accumulation (lower tertile) were labelled as Ovx-R and those in the upper tertile as Ovx-P.Results Ovx-R rats displayed similar abdominal fat gain to Sham rats whereas Ovx-P rats depicted abdominal fat mass twice as high as that of Sham and Ovx-R rats. Despite the difference in abdominal adiposity, liver fat content was similar to 50% higher (p < 0.01) in both Ovx-R and Ovx-P rats compared to Sham rats. In addition, both Ovx-R and Ovx-P rats depicted higher HOMA-IR scores (p < 0.05) and lower (p < 0.01) hepatic gene expression of leptin receptor-b and -e, microsomal transfer protein (MTP), and diacylglycerol acyltransferase-2 (DGAT-2) compared to Sham rats.Conclusion The present findings indicate that estrogen withdrawal-induced hepatic steatosis and associated insulin resistance may be dissociated from abdominal fat accumulation and suggest that a decrease in leptin action through a down-regulation of leptin receptors and a decrease in very low density lipoprotein production through a down-regulation of MTP and DGAT-2 may be factors responsible for this observation in the absence of peripheral fat gain.