UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency.
By J. Nedergaard, V. Golozoubova, A. Matthias, A. Asadi, A. Jacobsson, B. Cannon. Biochimica et Biophysica Acta, 2001
642 citations recorded by the source corpus.
The uniqueness of UCP1 (as compared to UCP2/UCP3) is evident from expression analysis and ablation studies. UCP1 expression is positively correlated with metabolic inefficiency, being increased by cold acclimation (in adults or perinatally) and overfeeding, and reduced in fasting and genetic obesity. Such a simple relationship is not observable for UCP2/UCP3. Studies with UCP1-ablated animals substantiate the unique role of UCP1: the phenomenon of adaptive adrenergic non-shivering thermogenesis in the intact animal is fully dependent on the presence of UCP1, and so is any kind of cold acclimation-recruited non-shivering thermogenesis; thus UCP2/UCP3 (or any other proteins or metabolic processes) cannot substitute for UCP1 physiologically, irrespective of their demonstrated ability to show uncoupling in reconstituted systems or when ectopically expressed. Norepinephrine-induced thermogenesis in brown-fat cells is absolutely dependent on UCP1, as is the uncoupled state and the recoupling by purine nucleotides in isolated brown-fat mitochondria. Although very high UCP2/UCP3 mRNA levels are observed in brown adipose tissue of UCP1-ablated mice, there is no indication that the isolated brown-fat mitochondria are uncoupled; thus, high expression of UCP2/UCP3 does not necessarily confer to the mitochondria of a tissue a propensity for being innately uncoupled. Whereas the thermogenic effect of fatty acids in brown-fat cells is fully UCP1-dependent, this is not the case in brown-fat mitochondria; this adds complexity to the issues concerning the mechanisms of UCP1 function and the pathway from beta(3)-adrenoceptor stimulation to UCP1 activation and thermogenesis. In addition to amino acid sequences conserved in all UCPs as part of the tripartite structure, all UCPs contain certain residues associated with nucleotide binding. However, conserved amongst all UCP1s so far sequenced, and without parallel in all UCP2/UCP3, are two sequences: 144SHLHGIKP and the C-terminal sequence RQTVDC(A/T)T; these sequences may therefore be essential for the unique thermogenic function of UCP1. The level of UCP1 in the organism is basically regulated at the transcriptional level (physiologically probably mainly through the beta(3)-adrenoceptor/CREB pathway), with influences from UCP1 mRNA stability and from the delay caused by translation. It is concluded that UCP1 is unique amongst the uncoupling proteins and is the only protein able to mediate adaptive non-shivering thermogenesis and the ensuing metabolic inefficiency.
Subfields: Cell Biology, Physiology, Rehabilitation
View Paper: https://www.semanticscholar.org/paper/f8056895f8fc9b512c9ace480f568ae91a16ffb1
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Citations in the corpus
- Adiponectin Regulation and Function (2018, positive): “Adiponectin directly increases UCP1 gene expression through activation of AMPK (115).”
- Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. (2013, neutral): “In rodents, the increase in NST can be fully attributed to BAT (9, 10).”
- UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. (2013, background): “These mitochondria oxidize substrate at high rates directlywhen it is added, through the inherent activity of UCP1 (Nedergaard et al., 2001).”
- Nonshivering thermogenesis and its adequate measurement in metabolic studies (2011, background): “The exact mechanism of this activation is still not fully resolved (Nedergaard et al., 2001).”
- Metabolism and function of coenzyme Q. (2004, background): “Five UCPs (1–5 in humans) are known and UCP1 is the most well characterized, present in brown adipose tissue where it participates in thermogenesis [67,68].”