Question

The physiological function of brown adipose tissue is to produce heat using a mitochondrial protein, thermogenin, also called uncoupling protein-1 (UCP-1). It was previously thought that in humans, uncoupling proteins (UCPs) were present only in newborn babies since adult humans lack brown fat; however, two other members of the uncoupling protein family, UCP2 and UCP3, were identified in adults. This was realized after investigators produced UCP1-knockout mice that were missing the gene for the UCP1 protein; even after knockout, they noticed that there was still finite proton leakage across the inner membrane that could not be explained by simple proton diffusion. Subsequent studies in transgenic mice showed that over expression of UCP3 results in reduced body weight gain and adiposity (even after they consumed more food). Because of studies such as these, UCPs are being studied as targets for treating obesity. In adults, UCP2 and UCP3 are expressed in white adipose tissue and skeletal muscle. Discuss how and why induction of UCP2 or UCP3 might be helpful in treating obesity and maintaining a constant amount of adipose tissue.

Answer 1

UCP2 or UCP3 acts as an uncoupling protein. They leak protons across inner mitochondrial membrane, thereby reducing the membrane potential.

All the nutrients from diet are categorically oxidized and electrons are extracted from those to pass them through the ETC(electron transport chain). This sets up a proton gradient across inner mitochondrial membrane, using which ATP is synthesized. In case of excess energy, fatty acids are synthesized from acetyl coA using the ATP molecules and stored in adipose tissue. If fat synthesis exceeds fat oxidation, then obesity might occur.

If UCP2 or UCP3 are induced to function at a higher level in adipose tissue, they will leak protons and reduce inner membrane potential, thereby dissipating metabolic energy. So less energy will be obtained from same amount of nutrients than before. This will enable less fat synthesis in cells even with same amount of intake of food. This is why, UCP2 and UCP3 are promising targets for obesity.