Professional Documents
Culture Documents
Experimental Physiology :
Non-shivering thermogenesis in brown adipose tissue is the main mechanism for thermoregulatory heat
production in small mammals and newborns. During cold acclimation the sympathetic innervation triggers
the recruitment of brown adipose tissue by hyperplasia, which involves the proliferation and differentiation of
precursor cells, and by hypertrophy of mature brown adipocytes. Mitochondrial biogenesis and increased
synthesis of the uncoupling protein 1 (UCP-1) are hallmarks of the thermogenic recruitment process. The
severalfold increase of mitochondrial protein content during cold acclimation recruits a large capacity for
oxidative phosphorylation. However, UCP-1 increases proton leakage across the inner membrane of brown
adipocyte mitochondria and thereby dissipates proton motive force as heat instead of ATP synthesis. During
recent years considerable progress has been achieved in the analysis of transcriptional mechanisms controlling
Ucp1 gene expression. However, so far only little is known about the molecular basis of cold-induced
mitochondrial biogenesis in brown adipose tissue. Experimental Physiology (2003) 88.1, 141148.
Abbreviations
AR, adrenergic receptor
c-FOS, immediate early gene (transcription factor)
COX, cytochrome c oxidase
CRE, cAMP response element
CREB, cAMP response element binding protein
DIO-2, deiodinase type 2
mtTFA, mitochondrial transcription factor
NF-E2, nuclear factor-erythroid 2
NFE212, member of the NF-E2 transcription factor family
NRF-1, nuclear respiratory factor 1
NRF-2, nuclear respiratory factor 2
NST, non-shivering thermogenesis
PGC-1, peroxisome proliferator-activated receptor g
coactivator
PPARg, peroxisome proliferator-activated receptor g
PPRE, PPAR response element
RAR, retinoic acid receptor
RARE, retinoic acid response element
RXR, retinoid X receptor
TR, thyroid receptor
TRE, thyroid hormone response element
UCP-1, uncoupling protein
Email: klingens@mailer.uni-marburg.de
Experimental Physiology :
142
M. Klingenspor
Experimental Physiology :
143
Experimental Physiology :
144
M. Klingenspor
Figure 1
Direct and indirect cAMP-dependent pathways involved in the transcriptional control of the Ucp1
enhancer at ~2.4 kb upstream of transcription start site.
Experimental Physiology :
Figure 2
Effect of 7 days cold exposure on
mitochondrial and nuclear gene
expression in brown adipose tissue of the
Djungarian hamster. The mRNA levels of
12S rRNA, COX-I and COX-III
(mitochondrial), COX-IV, COX-Va and
UCP-1 were quantified by slot blot
analysis and related to the 28S rRNA
hybridization signal. A two-sample t test
(unpaired) was applied to compare means;
* P < 0.05.
145
Experimental Physiology :
146
M. Klingenspor
Experimental Physiology :
147
148
M. Klingenspor
Experimental Physiology :
Acknowledgements
Many thanks to Gerhard Heldmaier, Carola Meyer, Christa von
Praun and Tatjana Schneider for helpful discussions and comments
on draft versions of this review. Our studies are supported by the
German Research Foundation (DFG).