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

Ingrid Wernstedt Asterholm, Dorothy I. Mundy, Jian Weng, Richard G W Anderson, Philipp E. Scherer

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)171-185
Number of pages15
JournalCell Metabolism
Volume15
Issue number2
DOIs
StatePublished - Feb 8 2012

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Caveolin 1
Adipose Tissue
Liver
Lipodystrophy
Aptitude
Gluconeogenesis
Adiponectin
Metabolic Networks and Pathways
Adipocytes
Fasting
Signal Transduction
Molecular Weight
Cell Membrane
Phenotype
Muscles

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1. / Wernstedt Asterholm, Ingrid; Mundy, Dorothy I.; Weng, Jian; Anderson, Richard G W; Scherer, Philipp E.

In: Cell Metabolism, Vol. 15, No. 2, 08.02.2012, p. 171-185.

Research output: Contribution to journalArticle

Wernstedt Asterholm, Ingrid ; Mundy, Dorothy I. ; Weng, Jian ; Anderson, Richard G W ; Scherer, Philipp E. / Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1. In: Cell Metabolism. 2012 ; Vol. 15, No. 2. pp. 171-185.
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