Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hepatology. 2010 Dec;52(6):2109-17. doi: 10.1002/hep.23920. Epub 2010 Oct 21.
We previously reported that mice subjected to partial hepatectomy exhibit rapid development of hypoglycemia followed by transient accumulation of fat in the early regenerating liver. We also showed that disrupting these metabolic alterations results in impaired liver regeneration. The studies reported here were undertaken to further characterize and investigate the functional importance of changes in systemic adipose metabolism during normal liver regeneration. The results showed that a systemic catabolic response is induced in each of two distinct, commonly used experimental models of liver regeneration (partial hepatectomy and carbon tetrachloride treatment), and that this response occurs in proportion to the degree of induced hepatic insufficiency. Together, these observations suggest that catabolism of systemic adipose stores may be essential for normal liver regeneration. To test this possibility, we investigated the hepatic regenerative response in fatty liver dystrophy (fld) mice, which exhibit partial lipodystrophy and have diminished peripheral adipose stores. The results showed that the development of hypoglycemia and hepatic accumulation of fat was attenuated and liver regeneration was impaired following partial hepatectomy in these animals. The fld mice also exhibited increased hepatic p21 expression and diminished plasma levels of the adipose-derived hormones adiponectin and leptin, which have each been implicated as regulators of liver regeneration.
These data suggest that the hypoglycemia that develops after partial hepatectomy induces systemic lipolysis followed by accumulation of fat derived from peripheral stores in the early regenerating liver, and that these events may be essential for initiation of normal liver regeneration.
我们之前曾报道过，部分肝切除的小鼠会迅速出现低血糖，并在早期再生肝脏中短暂积累脂肪。我们还表明，破坏这些代谢变化会导致肝再生受损。这里报告的研究旨在进一步描述和研究正常肝再生过程中系统脂肪代谢的变化及其功能重要性。结果表明，两种常用的肝再生实验模型（部分肝切除术和四氯化碳处理）中均诱导了全身性分解代谢反应，并且该反应与诱导的肝不全程度成比例。这些观察结果共同表明，全身脂肪储存的分解代谢可能是正常肝再生所必需的。为了验证这一可能性，我们研究了脂肪性肝营养不良（fld）小鼠的肝再生反应，这些小鼠表现出部分脂肪营养不良，并减少了外周脂肪储存。结果表明，这些动物在部分肝切除后，低血糖和肝脏脂肪积累的发展减弱，肝再生受损。fld 小鼠还表现出肝 p21 表达增加和血浆中脂肪衍生激素脂联素和瘦素水平降低，这两种激素都被认为是肝再生的调节剂。
这些数据表明，部分肝切除后出现的低血糖会诱导全身性脂肪分解，随后在外周储存的脂肪在早期再生肝脏中积累，这些事件可能对正常肝再生的启动至关重要。
