Furthermore, under these conditions CAV1 accumulates in the lipid droplet fraction in Alvelestat supplier wildtype mouse hepatocytes. Conclusion: Our data demonstrate that lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions. (HEPATOLOGY 2011) Liver regeneration is a remarkably rapid and efficient process by which remnant hepatocytes, normally a quiescent population
of cells, proliferate and restore the hepatic mass lost after chemical injury or partial hepatectomy.1-3 Studies examining the role of caveolin-1 (CAV1) during liver regeneration after partial hepatectomy in mice have produced contradictory results.4, 5 Using CAV1−/− mice developed in the Kurzchalia Laboratory (KCAV1−/− mice6) our research concluded that CAV1 plays an
important role in the modulation of cellular processes during the first hours of liver regeneration.4 KCAV1−/− mice failed to undergo liver regeneration and to accumulate hepatic lipid droplets and progression through the http://www.selleckchem.com/products/abt-199.html cell cycle was arrested before entering S-phase in KCAV1−/− hepatocytes. As blood glucose and hepatic glycogen levels decrease a few hours after partial hepatectomy, hepatic lipid metabolism becomes essential for hepatocytes to undergo proliferation.7 Therefore, we postulated that CAV1 plays an important role in the modulation of lipid metabolism during liver regeneration in mice. Consistent with this hypothesis, we demonstrated that the wildtype phenotype is rescued by supplementing the diet of KCAV1−/− mice with glucose MCE公司 prior to surgery and during regeneration. In contrast, a separate study in CAV1−/− outbred mice from Jackson Laboratories (JAXCAV1−/− mice) described that JAXCAV1−/− mice showed a higher index of regeneration than wildtype mice after partial hepatectomy and with no significant
effects on mouse survival after the operation, suggesting that CAV1 is not involved in liver regeneration.5 Here, by using three different strains of CAV1 null mice, we reassessed and confirmed the requirement of the expression of CAV1 in mice for efficient liver regeneration and lipid storage. 2-DG, 2-deoxy-glucose; ADRP, adipophilin; CAV1, caveolin-1; JAXCAV1−/−, mice provided by Jackson laboratory: KCAV1−/− and KCAV1+/+, CAV1 knockout and wildtype generated in the laboratory of Temo Kurzchalia; Balb/CCAV1−/− and Balb/CCAV1+/+ mice, CAV1 knockout and wildtype mice with a Balb/C genetic background; FASN, fatty acid synthase; G6PD, glucose-6-phosphate dehydrogenase; GyK, glycerol kinase; LD, lipid droplets; NEFA, nonesterified fatty acids; TAG, triacylglycerol; TLC, thin layer chromatography. KCAV1−/− mice were backcrossed onto a Balb/C background by mating KCAV1+/− females to wildtype Balb/C males (Animal Resources Centre, WA).