Abstract
Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD) or a high-fat diet (HFD). In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.
Highlights
Various physiological and behavioral oscillations, such as sleepwake cycles, body temperature, blood pressure, and hormone secretion, are associated with the circadian clock [1]
To address the question of whether body weight gain is affected by feeding behavior and the accompanying changes in peripheral circadian clock genes, we investigated the effects of feeding period restriction on body weight
Feeding period restrictions were divided into the following three groups: 1) ad libitum, in which mice were freely exposed to food; 2) restriction feeding in daytime (RF Day), in which mice could access food only in daytime; and 3) pair-feeding in nighttime (PF Night), in which mice were given the same amount of food as the RF Day group but only at night (Figure 1)
Summary
Various physiological and behavioral oscillations, such as sleepwake cycles, body temperature, blood pressure, and hormone secretion, are associated with the circadian clock [1]. Circadian oscillation is composed of auto-regulatory negative feedback loops; Bmal, Clock, Per, and Cry are key circadian transcription factors that produce rhythmic oscillations in a cell-autonomous manner. Bmal and Clock increase the mRNA levels of Rev-erba and RORa, which compete for binding to the retinoic acid-related orphan receptor response elements (ROREs) and repress or activate the expression of Bmal, respectively. This alternating promoter occupancy is due to the rhythmic expression of Rev-erba [2]. These autoregulatory loops are modulated by various post-translational modifications such as phosphorylation, sumoylation, acetylation, and ubiquitination [3,4,5]
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