Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese

@article{Enerbck1997MiceLM,
  title={Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese},
  author={Sven Enerb{\"a}ck and Anders Jacobsson and Elizabeth M. Simpson and Carmen Guerra and Hitoshi Yamashita and Mary-Ellen Harper and Leslie P. Kozak},
  journal={nature},
  year={1997},
  volume={387},
  pages={90-94}
}
The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation1. This process protects against cold2 and regulates energy balance3. Manipulation of thermogenesis could be an effective strategy against obesity4–9. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after… Expand
UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction
TLDR
It is found that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT, and global proteomic analysis reveals that this cascade induced by U CP1 deletion is associated with a dramatic reduction in electron transport chain abundance. Expand
Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice*
TLDR
It is demonstrated that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS, and the consequence of increased mitochondrial coupling in U CP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined. Expand
Cold tolerance of UCP1-ablated mice: a skeletal muscle mitochondria switch toward lipid oxidation with marked UCP3 up-regulation not associated with increased basal, fatty acid- or ROS-induced uncoupling or enhanced GDP effects.
TLDR
It is concluded that there is no evidence for an involvement of UCP3 in basal, fatty-acid- or superoxide-stimulated oxygen consumption or in GDP sensitivity, and adaptations observed would be congruent with adaptation to chronically enhanced muscle activity caused by incessant shivering in these mice. Expand
Brown adipose tissue specific lack of uncoupling protein 3 is associated with impaired cold tolerance and reduced transcript levels of metabolic genes
TLDR
Comparisons with mutant hamsters on a broad genetic background implicate that Ucp3 is necessary to sustain high metabolic rates in brown adipose tissue and suggest a reduced cold tolerance due to impaired nonshivering thermogenesis. Expand
Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance
TLDR
UCPs are known or supposed to participate in basal and regulatory thermogenesis, but their exact biochemical and physiological functions have yet to be elucidated; very recent data suggest an important role for the UCPs in the control of production of free radicals by mitochondria, and in response to oxidants. Expand
Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice.
TLDR
The results indicate that the role of brown fat in cold-induced thermogenesis cannot be substituted by increased energy expenditure in other tissues. Expand
Uncoupling protein 1 controls reactive oxygen species in brown adipose tissue
  • M. Jastroch
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
  • 2017
TLDR
Although the physiological consequences in UCP1 knockout mice have been almost exclusively attributed to thermogenesis, there may be further consequences on mitochondrial ROS biology and downstream effects that have been widely ignored. Expand
Mitochondrial uncoupling proteins and obesity: Molecular and genetic aspects of UCP1
TLDR
Other phenotypes of this mouse, the hyperphagia, extreme resistance to leptin administration, retinopathy and high residual content of brown adipocytes, suggest that the effects of the transgene may be more extensive than simply a 60% reduction in the number ofbrown adipocytes. Expand
Absence of uncoupling protein 3 at thermoneutrality influences brown adipose tissue mitochondrial functionality in mice
  • E. Silvestri, R. Senese, +10 authors A. Lombardi
  • Chemistry, Medicine
  • FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2020
TLDR
Data here reported show that the absence of UCP3 results in a significant alteration of BAT mitochondrial physiology and morphology, which could help to clarify some aspects of the association between metabolic disorders associated with low U CP3 levels, as previously reported in human studies. Expand
Increased mitochondrial proton leak in skeletal muscle mitochondria of UCP1-deficient mice.
TLDR
The overall kinetics of the mitochondrial proton leak, respiratory chain, and ATP turnover in skeletal muscle mitochondria from UCP1-deficient and heterozygous control mice indicate a thermogenic mechanism favoring the lean phenotype of the U CP1- deficient mouse. Expand
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