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Caveolin‐1 orchestrates the balance between glucose and lipid‐dependent energy metabolism: Implications for liver regeneration
Author(s) -
Alejandro FernándezRojo Manuel,
Restall Christina,
Ferguson Charles,
Martel Nick,
Martin Sally,
Bosch Marta,
Kassan Adam,
Leong Gary M.,
Martin Sheree D.,
McGee Sean L.,
Muscat George E.O.,
Anderson Robin L.,
Enrich Carlos,
Pol Albert,
Parton Robert G.
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24810
Subject(s) - lipid metabolism , glycolysis , biology , hepatocyte , liver regeneration , steatosis , endocrinology , medicine , lipogenesis , anabolism , carbohydrate metabolism , microbiology and biotechnology , caveolin 1 , regeneration (biology) , metabolism , biochemistry , in vitro
Caveolin‐1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis. Using newly generated pure Balb/C CAV1 null ( Balb/C CAV1−/−) mice, CAV1−/− mice from Jackson Laboratories ( JAX CAV1−/−), and CAV1−/− mice developed in the Kurzchalia Laboratory ( K CAV1−/−), we show that under physiological conditions CAV1 expression in mouse tissues is necessary to guarantee an efficient progression of liver regeneration and mouse survival after partial hepatectomy. Absence of CAV1 in mouse tissues is compensated by the development of a carbohydrate‐dependent anabolic adaptation. These results were supported by extracellular flux analysis of cellular glycolytic metabolism in CAV1‐knockdown AML12 hepatocytes, suggesting cell autonomous effects of CAV1 loss in hepatic glycolysis. Unlike in K CAV1−/− livers, in JAX CAV1−/− livers CAV1 deficiency is compensated by activation of anabolic metabolism (pentose phosphate pathway and lipogenesis) allowing liver regeneration. Administration of 2‐deoxy‐glucose in JAX CAV1−/− mice indicated that liver regeneration in JAX CAV1−/− mice is strictly dependent on hepatic carbohydrate metabolism. Moreover, with the exception of regenerating JAX CAV1−/− livers, expression of CAV1 in mice is required for efficient hepatic lipid storage during fasting, liver regeneration, and diet‐induced steatosis in the three CAV1−/− mouse strains. Furthermore, under these conditions CAV1 accumulates in the lipid droplet fraction in wildtype mouse hepatocytes. Conclusion: Our data demonstrate that lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions. (H EPATOLOGY 2011)