Caveolin-1-ablated mice survive in cold by nonshivering thermogenesis despite desensitized adrenergic responsiveness.
Caveolin-1 (Cav1)-ablated mice display impaired lipolysis in white adipose tissue. They also seem to have an impairment in brown adipose tissue function, implying that Cav1-ablated mice could encounter problems in surviving longer periods in cold temperatures. To investigate this, Cav1-ablated mice and wild-type mice were transferred to cold temperatures for extended periods of time, and parameters related to metabolism and thermogenesis were investigated. Unexpectedly, the Cav1-ablated mice survived in the cold. There were no differences between Cav1-ablated and wild-type mice with regard to food intake, in behavior related to shivering, or in body temperature. The Cav1-ablated mice had a halved total fat content independently of acclimation temperature. There was no difference in brown adipose tissue uncoupling protein-1 (UCP1) protein amount, and isolated brown fat mitochondria were thermogenically competent but displayed 30% higher thermogenic capacity. However, the beta(3)-adrenergic receptor amount was reduced by about one-third in the Cav1-ablated mice at all acclimation temperatures. Principally in accordance with this, a higher than standard dose of norepinephrine was needed to obtain full norepinephrine-induced thermogenesis in the Cav1-ablated mice; the higher dose was also needed for the Cav1-ablated mice to be able to utilize fat as a substrate for thermogenesis. In conclusion, the ablation of Cav1 impairs brown adipose tissue function by a desensitization of the adrenergic response; however, the desensitization is not evident in the animal as it is overcome physiologically, and Cav1-ablated mice can therefore survive in prolonged cold by nonshivering thermogenesis.
Dept. of Physiology, Wenner-Gren Institute, Stockholm Univ., Sweden.
Charlotte L
CL
Mattsson
Robert I
RI
Csikasz
Irina G
IG
Shabalina
Jan
J
Nedergaard
Barbara
B
Cannon
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001481:Basal Metabolism; D001823:Body Composition; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002153:Calorimetry, Indirect; D051242:Caveolin 1 / Q000502:physiology*; D003080:Cold Temperature; D004435:Eating / Q000502:physiology; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology*
D051242:Caveolin 1; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine