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Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1.

Caveolin-1 is a major structural component of raft structures within the plasma membrane and has been implicated as a regulator of cellular signal transduction with prominent expression in adipocytes. Here, we embarked on a comprehensive characterization of the metabolic pathways dysregulated in caveolin-1 null mice. We found that these mice display decreased circulating levels of total and high molecular weight adiponectin and a reduced ability to change substrate use in response to feeding/fasting conditions. Caveolin-1 null mice are extremely lean but retain muscle mass despite lipodystrophy and massive metabolic dysfunction. Hepatic gluconeogenesis is chronically elevated, while hepatic steatosis is reduced. Our data suggest that the complex phenotype of the caveolin-1 null mouse is caused by altered metabolic and mitochondrial function in adipose tissue with a subsequent compensatory response driven mostly by the liver. This mouse model highlights the central contributions of adipose tissue for system-wide preservation of metabolic flexibility.

Pubmed ID: 22326219

Authors

  • Asterholm IW
  • Mundy DI
  • Weng J
  • Anderson RG
  • Scherer PE

Journal

Cell metabolism

Publication Data

February 8, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM 52016
  • Agency: NHLBI NIH HHS, Id: HL 20948
  • Agency: NIDDK NIH HHS, Id: P01 DK088761
  • Agency: NIDDK NIH HHS, Id: P01 DK088761-02
  • Agency: NIDDK NIH HHS, Id: P01DK088761-01
  • Agency: NIDDK NIH HHS, Id: R01 DK055758
  • Agency: NIDDK NIH HHS, Id: R01 DK055758-12
  • Agency: NCI NIH HHS, Id: R01-CA112023
  • Agency: NIDDK NIH HHS, Id: R01-DK55758
  • Agency: NIDDK NIH HHS, Id: RC1 DK086629
  • Agency: NIDDK NIH HHS, Id: RC1 DK086629
  • Agency: NIDDK NIH HHS, Id: RC1 DK086629-02

Mesh Terms

  • Adiponectin
  • Adipose Tissue
  • Animals
  • Caveolin 1
  • Fatty Acids, Nonesterified
  • Fatty Liver
  • Gluconeogenesis
  • Histological Techniques
  • Liver
  • Metabolic Networks and Pathways
  • Mice
  • Mitochondria
  • Tomography, X-Ray Computed