Dept. of Gastroenterology and Pathobiology, Cleveland Clinic Foundation, Lerner Research Institute, OH 44195, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4):G731-8. doi: 10.1152/ajpgi.00161.2011. Epub 2011 Jul 28.
The portacaval anastamosis (PCA) rat is a model to examine nutritional consequences of portosystemic shunting in cirrhosis. Alterations in body composition and mechanisms of diminished fat mass following PCA were examined. Body composition of male Sprague-Dawley rats with end-to-side PCA and pair-fed sham-operated (SO) controls were studied 3 wk after surgery by chemical carcass analysis (n=8 each) and total body electrical conductivity (n=6 each). Follistatin, a myostatin antagonist, or vehicle was administered to PCA and SO rats (n=8 in each group) to examine whether myostatin regulated fat mass following PCA. The expression of lipogenic and lipolytic genes in white adipose tissue (WAT) was quantified by real-time PCR. Body weight, fat-free mass, fat mass, organ weights, and food efficiency were significantly lower (P < 0.001) in the PCA than SO rats. Adipocyte size and triglyceride content of epididymal fat in PCA rats were significantly lower (P < 0.01) than in SO rats. Myostatin expression was higher in the WAT of PCA compared with SO rats and was accompanied by an increase in phospho-AMP kinase Thr(172). Follistatin increased whole body fat and WAT mass, adipocyte size, and expression of lipogenic genes in WAT in PCA, but not in SO rats. Myostatin and phospho-AMP kinase protein and lipolytic gene expression were lower with follistatin. We conclude that PCA results in loss of fat mass due to an increased expression of myostatin in adipose tissue with lower lipogenic and higher fatty acid oxidation gene expression.
腔静脉吻合（PCA）大鼠是一种研究门体分流性肝硬化营养后果的模型。本研究检测了 PCA 后身体成分的改变及其脂肪量减少的机制。3 周后，通过化学尸检分析（每组 8 只）和全身电导率（每组 6 只）研究了侧侧 PCA 雄性 Sprague-Dawley 大鼠的身体成分，同时对假手术（SO）对照大鼠进行了研究。将肌生成抑制素拮抗剂 follistatin 或载体给予 PCA 和 SO 大鼠（每组 8 只），以研究肌生成抑制素是否调节 PCA 后的脂肪量。通过实时 PCR 定量检测白色脂肪组织（WAT）中的生脂和脂解基因表达。与 SO 大鼠相比，PCA 大鼠的体重、去脂体重、脂肪量、器官重量和食物效率均显著降低（P < 0.001）。PCA 大鼠的附睾脂肪的脂肪细胞大小和甘油三酯含量显著低于 SO 大鼠（P < 0.01）。与 SO 大鼠相比，PCA 大鼠的 WAT 中肌生成抑制素表达更高，磷酸化 AMP 激酶 Thr（172）也增加。Follistatin 增加了 PCA 大鼠的全身脂肪和 WAT 质量、脂肪细胞大小和 WAT 中生脂基因的表达，但在 SO 大鼠中没有。Follistatin 降低了肌生成抑制素和磷酸化 AMP 激酶蛋白以及脂肪分解基因的表达。我们得出结论，PCA 导致脂肪量减少，原因是脂肪组织中肌生成抑制素表达增加，生脂基因表达降低，脂肪酸氧化基因表达增加。
