title: Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration.
abstract: 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.
  
  
  CONCLUSIONS
  Our data demonstrate that lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions.
authors: Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
authors: Manuel Alejandro
authors: MA
authors: Fernández-Rojo
authors: Christina
authors: C
authors: Restall
authors: Charles
authors: C
authors: Ferguson
authors: Nick
authors: N
authors: Martel
authors: Sally
authors: S
authors: Martin
authors: Marta
authors: M
authors: Bosch
authors: Adam
authors: A
authors: Kassan
authors: Gary M
authors: GM
authors: Leong
authors: Sheree D
authors: SD
authors: Martin
authors: Sean L
authors: SL
authors: McGee
authors: George E O
authors: GE
authors: Muscat
authors: Robin L
authors: RL
authors: Anderson
authors: Carlos
authors: C
authors: Enrich
authors: Albert
authors: A
authors: Pol
authors: Robert G
authors: RG
authors: Parton
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001774:Blood Chemical Analysis; D051242:Caveolin 1 / Q000378:metabolism*; D049109:Cell Proliferation; D002855:Chromatography, Thin Layer / Q000379:methods; D003847:Deoxyglucose / Q000494:pharmacology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology; D006706:Homeostasis; D050356:Lipid Metabolism / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D051242:Caveolin 1; D003847:Deoxyglucose; D005947:Glucose