Food deprivation during active phase induces skeletal muscle atrophy via IGF-1 reduction in mice.

ABSTRACT

Skeletal muscle mass is largely influenced by nutritional status and physical activity. Although feeding at specific times of the day (time-restricted feeding, TRF) modulates obesity and other metabolic functions, its effects on skeletal muscles remain unclear. We explored the effects of feeding mice only during the inactive (daytime feeding, DF) or active (nighttime feeding, NF) phases for one week. Daytime feeding did not abolish the nocturnal activity rhythm, although total daily activity was reduced in these mice. Temporal expression of the circadian clock genes, Per2 and Rev-erbα, became synchronized to the feeding cycle in the liver, but not in skeletal muscle. Skeletal muscle mass, grip strength, and cross-sectional area were significantly lower in DF, than in NF mice, although DF increased body weight gain and lipid accumulation. Expression of the atrophy-related ubiquitin ligases, Atrogin-1 and Murf1 and the autophagy-related genes, Lc3b and Bnip3, was induced during the active phase in the gastrocnemius muscles of DF, compared with those of NF mice. Plasma IGF-1 concentrations and Igf-1 expression in the livers and gastrocnemius muscles during the active phase were lower in DF, than in NF mice. Furthermore, exogenous IGF-1 injection significantly suppressed DF-induced reduction in gastrocnemius muscle mass, which might at least partly explain the association between decreased plasma IGF-1 concentrations and reductions in the skeletal muscle mass of DF mice. These findings suggest that feeding only during the inactive phase reduces skeletal muscle mass via a decrease in plasma IGF-1 concentrations during the active phase.