The Economist 14-20 May 2011 by The Economist Group

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89 Chen JJ, Yu BP: Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med 1994;17:411–418. 90 Drew B, Phaneuf S, Dirks A, Selman C, Gredilla R, Lezza A, Barja G, Leeuwenburgh C: Effects of aging and caloric restriction on mitochondrial energy production in gastrocnemius muscle and heart. Am J Physiol Regul Integr Comp Physiol 2003;284:R474–R480. 91 Zainal TA, Oberley TD, Allison DB, Szweda LI, Weindruch R: Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle.

The metabolic shifts observed are consistent with this, including the increased expression of the ␤3-adrenergic receptor and UCP3. In white adipose tissue, activation of the ␤-adrenergic receptors leads to mobilization of fat stores and regulates the release of several adipokines [128]. In brown fat, ␤-adrenergic receptor activation leads to increased expression of the thermogenic uncoupler UCP1 via p38 and the transcriptional coactivator PGC-1␣ [129]. Ordinarily, PGC-1␣ protein levels are barely detectable in white adipose tissue but are increased in white adipose tissue from DR animals [unpubl.

Although the physiological role of UCP3 is controversial [68–70], increased UCP3 expression augments FAO and decreases ROS production without uncoupling respiration [71] and enhances the capacity for fatty Anderson/Weindruch 24 acid transport and FAO in skeletal muscle [72]. These data argue that UCP3 is not merely a mitochondrial uncoupling protein involved in the regulation of the proton leak. Elevated free fatty acids induce UCP3 expression consistent with UCP3 playing a role in the use of free fatty acid as a fuel [73].