Department of Digestive and Lifestyle-Related Diseases, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Biochem Biophys Res Commun. 2011 Apr 1;407(1):163-8. doi: 10.1016/j.bbrc.2011.02.131. Epub 2011 Mar 1.
Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Male Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-α were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-α, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-β1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-β1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result from altered metabolic gene expression profiles and potential dysregulation of TGF-β1 expression.
肝脂肪变性（HS）对肝再生有负面影响，但不同的 HS 病理生理学可能导致不同的结果。雄性 Sprague-Dawley 大鼠用高果糖（66%果糖；H-fruc）、高脂肪（54%脂肪；H-fat）或对照饲料喂养 4 周。根据肝甘油三酯含量和油红 O 染色，H-fruc 组发生 HS，但与 H-fat 组相比，程度较轻。与 H-fat 组相比，H-fruc 组肝脂肪酸合酶和果糖激酶的 mRNA 表达水平升高，肉碱棕榈酰转移酶-1 和过氧化物酶体增殖物激活受体-α的表达水平降低。通过测量术后肝质量和 PCNA 阳性肝细胞的增加来评估 70%部分肝切除（PHx）后的肝再生，与 H-fat 和对照组相比，H-fruc 组在第 3 天和第 7 天的肝再生受损。PHx 后血清肿瘤坏死因子-α、白细胞介素-6 和肝细胞生长因子水平没有明显变化。相比之下，与 PHx 前 0 天相比，H-fat 组 PHx 后第 3 天和对照组第 1 天血清 TGF-β1 水平略有但显著降低，然后逐渐升高。然而，H-fruc 组在 PHx 后血清 TGF-β1 水平没有变化。这些结果表明，HS 后 PHx 肝再生受损与脂肪变性的原因有关，而不是程度。这种差异可能是由于代谢基因表达谱的改变和 TGF-β1 表达的潜在失调所致。
