Time-imposed daily restricted feeding induces rhythmic expression of Fgf21 in white adipose tissue of mice

Aug 13, 2011Biochemical and biophysical research communications

Daily timed feeding causes regular daily changes in a hormone gene in mouse body fat

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Abstract

An 80-fold increase in Fgf21 mRNA expression was observed in adipose tissue of mice subjected to four hours of daily restricted feeding.

Fgf21 expression is regulated by feeding patterns and the circadian clock in the liver.
Refeeding after fasting significantly increases Fgf21 expression in adipose tissue, while fasting alone does not.
Hepatic Fgf21 expression induced by fasting is completely reversed upon refeeding.
FGF21 does not appear to be necessary for the central circadian clock or the food-entrainable oscillator in mice.
Circadian gene expression profiles were similar in wild-type and Fgf21 knockout mice under restricted feeding conditions.

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Fibroblast growth factor 21 (FGF21) is a key metabolic regulator that is induced by fasting and starvation, and its expression is thought to be regulated by the circadian clock in the liver. To evaluate the functional role of FGF21 in the circadian regulation of physiology and behavior, we examined the temporal expression profiles of Fgf21 and circadian clock genes in addition to behavioral activity rhythms under adlibitum feeding (ALF) and time-imposed restricted feeding (RF) in mice. Four hours of daily restricted feeding during the daytime induced over an 80-fold increase in feeding-dependent rhythmic Fgf21 mRNA expression in epididymal white adipose tissue (eWAT), although the expression levels were continuously increased 10-fold in the liver of wild-type (WT) mice. Refeeding subsequent to transient fasting revealed that refeeding but not fasting remarkably induces Fgf21 expression in eWAT, although fasting-induced hepatic Fgf21 expression is completely reversed by refeeding. The free-running period of locomotor activity rhythm under ALF and the food anticipatory activity (FAA) under RF remained intact in Fgf21 knockout (KO) mice, suggesting that FGF21 is dispensable for both the central clock in the suprachiasmatic nucleus (SCN) and the food-entrainable oscillator that governs the FAA. Temporal expression profiles of circadian genes such as mPer2 and BMAL1 were essentially identical in both tissues between WT and Fgf21 KO mice under RF. The physiological role of the refeeding-induced adipose Fgf21 expression remains to be elucidated.

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Time-imposed daily restricted feeding induces rhythmic expression of Fgf21 in white adipose tissue of mice

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