Caveolin-1 expression is essential for proper nonshivering thermogenesis in brown adipose tissue.
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 degrees 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.
Cohen
Alex W
AW
Department of Molecular Pharmacology, The Albert Einstein Cancer Center, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Schubert
William
W
Brasaemle
Dawn L
DL
Scherer
Philipp E
PE
Lisanti
Michael P
MP
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000502:physiology*; D003080:Cold Temperature; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005508:Food Deprivation / Q000502:physiology; D015870:Gene Expression; D008066:Lipolysis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000648:ultrastructure; D022722:Thermogenesis / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides