1 Enthusiasm for further characterization of functional significa

1 Enthusiasm for further characterization of functional significance of new genes and cell signaling pathways remains high because of the potential for finding novel therapies to stimulate liver regeneration in acute and chronic liver diseases that negatively

impact liver regeneration. The report by Gazit et al. in this issue of Hepatology offers new insights into mechanisms of liver regeneration focusing on PI3K Inhibitor Library the contribution of peripheral lipid stores and systemic lipolysis in the liver’s ability to regenerate in response to 70% partial hepatectomy.7 The present study was prompted by previous observations that partial hepatectomy induces transient hypoglycemia followed by lipid accumulation within hepatocytes that precedes the time of peak hepatocyte proliferation in mice. The authors previously reported that pharmacologic and genetic interventions that suppress the early induction of transient hypoglycemia and hepatic steatosis are able to inhibit liver regeneration in mice.8-10 They reason that the early induction of hypoglycemia may be a potential trigger for the release of fatty acids from peripheral lipid stores and that fatty acids derived from peripheral adipose tissues, in turn, may be responsible for transient lipid accumulation within hepatocytes in

regenerating livers (Fig. 1). To test their hypothesis that catabolism of systemic

adipose stores are essential for liver regeneration, the authors performed 70% partial hepatectomy on fatty liver dystrophy (fld) mice, which exhibit partial lipodystrophy and have diminished http://www.selleckchem.com/products/DMXAA(ASA404).html peripheral adipose MCE公司 stores. Supporting their hypothesis, fld mice exhibited attenuated development of hypoglycemia, hepatic lipid accumulation, and impaired hepatocyte proliferation in response to 70% partial hepatectomy.7 They conclude that hepatic insufficiency is the primary trigger for the induction of a systemic catabolic response based on their observation in two independent experimental models, partial hepatectomy, and carbon tetrachloride–mediated injury in mice. Data presented in this study supports the notion that catabolism of total body and fat mass after partial hepatectomy occurs in proportion to the degree of induced hepatic insufficiency. However, the decline in lean mass did not correlate with the extent of hepatic insufficiency induced after one-third versus two-thirds partial hepatectomy.7 These findings provide direction for future studies to address key questions pertaining to liver:body mass regulation and identification of relevant body mass compartments that impact growth responses in the liver. Maintenance of metabolic homeostasis by balancing extrahepatic energy consumption with dietary nutrient uptake is one of the essential functions of the liver.

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