Caloric restriction and exercise "mimetics'': Ready for prime time? - PubMed (original) (raw)

Review

Caloric restriction and exercise "mimetics'': Ready for prime time?

Christoph Handschin. Pharmacol Res. 2016 Jan.

Abstract

Exercise and diet are powerful interventions to prevent and ameliorate various pathologies. The development of pharmacological agents that confer exercise- or caloric restriction-like phenotypic effects is thus an appealing therapeutic strategy in diseases or even when used as life-style and longevity drugs. Such so-called exercise or caloric restriction "mimetics" have so far mostly been described in pre-clinical, experimental settings with limited translation into humans. Interestingly, many of these compounds activate related signaling pathways, most often postulated to act on the common downstream effector peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle. In this review, resveratrol and other exercise- and caloric restriction "mimetics" are discussed with a special focus on feasibility, chances and limitations of using such compounds in patients as well as in healthy individuals.

Keywords: (−)-Epicatechin (PubChem CID 72276); AICAR (PubChem CID 266934); AMPK; Caloric restriction; Celastrol (PubChem CID 122724); Diet; Exercise; GSK4716 (PubChem CID 5399376); GW1516 (PubChem ID 9803963); Metformin (PubChem CID 4091); Mimetics; Nicotinamide riboside (PubChem CID 439924); PGC-1α; PPARβ/δ; Rapamycin (PubChem CID 5040); Resveratrol; Resveratrol (PubChem CID 445154); SR9009 (PubChem ID 57394020); SRT1720 (PubChem ID 25232708); Skeletal muscle; Ursolic acid (PubChem CID 64945).

Copyright © 2015 Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1. Common and distinct effects of exercise and caloric restriction.

Even though exercise and caloric restriction affect energy intake (at least in some individuals) and expenditure in a diametrically opposite manner, the shared regulation of a number of phenotypic changes in skeletal muscle and potentially other tissues could underlie the similar health benefits of both interventions. Importantly however, other effects, e.g. on muscle and cardiovascular function as well as body weight, are predominantly observed after exercise and caloric restriction, respectively.

Figure 2

Figure 2. Molecular signaling of exercise and caloric restriction “mimetics” centered on PGC-1α.

Proposed mechanisms of action of several exercise and caloric restriction “mimetics” are depicted. * indicates coactivation of the respective transcription factors by PGC-1α. See text for details and abbreviations.

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