Editors' ChoiceMetabolism

Phasing Out Fat

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Science's STKE  27 Jun 2006:
Vol. 2006, Issue 341, pp. tw212
DOI: 10.1126/stke.3412006tw212

The protein known as TRB3 is a pseudokinase (a kinase-like protein that lacks kinase activity) synthesized in fasting animals. TRB3 modulates insulin signaling and is related to a Drosophila protein that coordinates mitosis and morphogenesis during development. Qi et al. find that overexpression of TRB3 in mice confers resistance to diet-induced obesity. This effect appears to be the result of decreased activity of acetyl-coenzyme A carboxylase (ACC) and consequent decreased synthesis of fatty acids. TRB3 directly interacts with ACC to promote its degradation via the E3 ubiquitin ligase constitutive photomorphogenic protein 1. Understanding the regulation of lipid metabolism may promote therapeutic strategies for the control of obesity.

L. Qi, J. E. Heredia, J. Y. Altarejos, R. Screaton, N. Goebel, S. Niessen, I. X. MacLeod, C. W. Liew, R. N. Kulkarni, J. Bain, C. Newgard, M. Nelson, R. M. Evans, J. Yates, M. Montminy, TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312, 1763-1766 (2006). [Abstract] [Full Text]

J. G. Neels, J. M. Olefsky, A new way to burn fat. Science 312, 1756-1758 (2006). [Summary] [Full Text]