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

First Author  Asterholm IW Year  2012
Journal  Cell Metab Volume  15
Issue  2 Pages  171-85
PubMed ID  22326219 Mgi Jnum  J:182288
Mgi Id  MGI:5315185 Doi  10.1016/j.cmet.2012.01.004
Citation  Asterholm IW, et al. (2012) Altered mitochondrial function and metabolic inflexibility associated with loss of caveolin-1. Cell Metab 15(2):171-85
abstractText  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.
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