title: The functional significance of the skeletal muscle clock: lessons fromBmal1knockout models.
abstract: The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using differentBmal1knockout (KO) models. A comparative analysis of these models reveals that the dramatic muscle wasting and premature aging caused by global conventional KO are not present in muscle-specificBmal1KO or in globalBmal1KO induced in the adult, therefore must reflect the loss ofBmal1function during development in non-muscle tissues. On the other hand, muscle-specificBmal1knockout causes impaired muscle glucose uptake and metabolism, supporting a major role of the muscle clock in anticipating the sleep-to-wake transition, when glucose becomes the predominant fuel for the skeletal muscle.
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy.
authors.forename: Stefano
authors.identifier: 0000-0002-5607-6421
authors.initials: S
authors.lastname: Schiaffino
authors.affiliation: Venetian Institute of Molecular Medicine (VIMM), Via Orus 2, 35129 Padova, Italy ; Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Bert
authors.initials: B
authors.lastname: Blaauw
authors.affiliation: Molecular Endocrinology, Institute for Diabetes and Obesity, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dyar
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D057906:Circadian Clocks; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D018345:Mice, Knockout; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D005947:Glucose
keywords: Bmal1 knockout; Circadian rhythms; Glucose metabolism; Glucose uptake; Muscle clock; Muscle denervation; Skeletal muscle