title: Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding.
abstract: Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat.
authors.affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.
authors.forename: Paula B M
authors.initials: PB
authors.lastname: De Andrade
authors.affiliation: Pharmaceutical Biochemistry, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Neff
authors.affiliation: Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Strosova
authors.affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Arsenijevic
authors.affiliation: Pharmaceutical Biochemistry, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland ; Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Patthey-Vuadens
authors.affiliation: Pharmaceutical Biochemistry, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scapozza
authors.affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Montani
authors.affiliation: Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Urs T
authors.initials: UT
authors.lastname: Ruegg
authors.affiliation: Department of Medicine, Physiology, University of Fribourg Fribourg, Switzerland.
authors.forename: Abdul G
authors.initials: AG
authors.lastname: Dulloo
authors.affiliation: Pharmaceutical Biochemistry, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland ; Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Dorchies
keywords: catch-up growth; contraction-relaxation; deiodinase; obesity; rat; skeletal muscle; thermogenesis; weight regain