Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism : implications for liver regeneration

Fernandez-Rojo, Manuel Alejandro, 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 and Parton, Robert G. 2012, Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism : implications for liver regeneration, Hepatology, vol. 55, no. 5, pp. 1574-1584, doi: 10.1002/hep.24810.

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Title Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism : implications for liver regeneration
Author(s) Fernandez-Rojo, Manuel Alejandro
Restall, Christina
Ferguson, Charles
Martel, Nick
Martin, Sally
Bosch, Marta
Kassan, Adam
Leong, Gary M.
Martin, Sheree D.
McGee, Sean L.ORCID iD for McGee, Sean L.
Muscat, George E. O.
Anderson, Robin L.
Enrich, Carlos
Pol, Albert
Parton, Robert G.
Journal name Hepatology
Volume number 55
Issue number 5
Start page 1574
End page 1584
Total pages 11
Publisher John Wiley & Sons
Place of publication Hoboken, N. J.
Publication date 2012-05
ISSN 0270-9139
Keyword(s) caveolin 1
Summary Caveolin-1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis. Using newly generated pure Balb/C CAV1 null (Balb/CCAV1−/−) mice, CAV1−/− mice from Jackson Laboratories (JAXCAV1−/−), and CAV1−/− mice developed in the Kurzchalia Laboratory (KCAV1−/−), 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 KCAV1−/− livers, in JAXCAV1−/− livers CAV1 deficiency is compensated by activation of anabolic metabolism (pentose phosphate pathway and lipogenesis) allowing liver regeneration. Administration of 2-deoxy-glucose in JAXCAV1−/− mice indicated that liver regeneration in JAXCAV1−/− mice is strictly dependent on hepatic carbohydrate metabolism. Moreover, with the exception of regenerating JAXCAV1−/− 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.
Language eng
DOI 10.1002/hep.24810
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
Grant ID NHMRC 1030474
Persistent URL

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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