Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration.
Journal - Hepatology (Baltimore, Md.)
To better understand the contribution of the role of caveolin-1 (CAV1) in liver physiology during liver regeneration and hepatic steatosis, we have generated CAV1 null (CAV1-/-) mouse with a pure genetic background. Study of these mice in comparison with another two different CAV1-/- mouse strains demonstrates that: i) upon regular physiological conditions expression of CAV1 in mouse tissues is necessary to guarantee an efficient progression of liver regeneration and mice survival after partial hepatectomy. ii) Expression of CAV1 in mice is required for efficient hepatic lipid storage during physiological and pathological conditions of hepatic steatosis and iii) Under these conditions CAV1 accumulates in the lipid droplet (LD) fraction in wild-type mouse hepatocytes. Interestingly, our comparative analysis also demonstrates that the absence of CAV1 in mouse tissues can be compensated by the development of a carbohydrate-dependent anabolic adaptation that in the case of the liver determines the ability of hepatocytes to undergo liver regeneration. These results were supported by extracellular flux analysis of cellular glycolytic metabolism in CAV1-knock-down AML12 hepatocytes suggesting cell autonomous effects of CAV1 loss in hepatic glycolysis. CONCLUSION: Here we demonstrate the extreme importance of the expression of CAV1 in mouse tissues for the metabolism and cell biology of hepatocytes under physiological and pathological conditions. (HEPATOLOGY 2011.).Copyright © 2011 American Association for the Study of Liver Diseases.