UCP2 and UCP3 in muscle controlling body metabolism.
The uncoupling protein-1 (UCP1) homologues UCP2 and UCP3 are able to uncouple ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting energy metabolism efficiency. In contrast to UCP1, which plays an important role in adaptive thermogenesis, UCP2 and UCP3 do not have a primary role in the regulation of energy metabolism. UCP2, which is expressed in a wide variety of tissues, including white adipose tissue, skeletal muscle and tissues of the immune system, has been suggested to affect the production of reactive oxygen species. UCP2 has also been suggested to regulate the [ATP]/[ADP] ratio and was recently shown to influence insulin secretion in the beta-cells of the pancreas. UCP3, in contrast, is expressed predominantly in skeletal muscle and has been associated with whole-body energy metabolism. However, the primary function of UCP3 is not the regulation of energy metabolism. For example, fasting, a condition attenuating energy expenditure, upregulates UCP3 expression. Moreover, UCP3-knockout mice have a normal metabolic rate. The exact function of UCP3 therefore remains to be elucidated, but putative roles for UCP3 include involvement in the regulation of ROS, in mitochondrial fatty acid transport and in the regulation of glucose metabolism in skeletal muscle. Whatever the primary function of these novel uncoupling proteins, a secondary effect via uncoupling might allow them to influence (but not to regulate) energy metabolism, which would be consistent with the observations from linkage and association studies. Therefore, UCP2 and UCP3 remain interesting targets for pharmacological upregulation in the treatment of obesity and diabetes.
Nutrition and Toxicology Research Institute Maastricht (NUTRIM) Department of Human Biology, Maastricht University, The Netherlands. p.schrauwen@hb.unimaas.nl
Patrick
P
Schrauwen
Matthijs
M
Hesselink
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014475:Uncoupling Agents / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate