Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown adipose tissue

Alex W. Cohen, William Schubert, Dawn L. Brasaemle, Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Recently, we have shown that loss of caveolin-1 leads to marked alterations in insulin signaling and lipolysis in white adipose tissue. However, little is known about the role of caveolin-1 in brown adipose tissue (BAT), a tissue responsible for nonshivering thermogenesis. Here, we show that caveolin-1 null mice have a mildly, yet significantly, decreased resting core body temperature. To investigate this in detail, we next subjected the mice to fasting (for 24 h) or cold treatment (4°C for 24 h), individually or in combination. Interestingly, caveolin-1 null mice showed markedly decreased body temperatures in response to fasting or fasting/cold treatment; however, cold treatment alone had no effect. In addition, under these conditions caveolin-1 null mice failed to show the normal increase in serum nonesterified fatty acids induced by fasting or fasting/cold treatment, suggesting that these mice are unable to liberate triglyceride stores for heat production. In accordance with these results, the triglyceride content of BAT was reduced nearly 10-fold in wild-type mice after fasting/ cold treatment, but it was reduced only 3-fold in caveolin-1 null mice. Finally, electron microscopy of adipose tissue revealed dramatic perturbations in the mitochondria of caveolin-1 null interscapular brown adipocytes. Taken together, our data provide the first molecular genetic evidence that caveolin-1 plays a critical functional and structural role in the modulation of thermogenesis via an effect on lipid mobilization.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalDiabetes
Volume54
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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