Effects of Irregular Feeding on the Daily Fluctuations in mRNA Expression of the Neurosecretory Protein GL and Neurosecretory Protein GM Genes in the Mouse Hypothalamus.

Atsuki Kadota,Eiko Iwakoshi-Ukena,Yuki Narimatsu,Keisuke Fukumura,Kenshiro Shikano,Megumi Furumitsu,Kazuyoshi Ukena

doi:10.3390/ijms22042109

Atsuki Kadota, Eiko Iwakoshi-Ukena + Show 5 more

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https://doi.org/10.3390/ijms22042109

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Abstract

Circadian desynchrony induced by a long period of irregular feeding leads to metabolic diseases, such as obesity and diabetes mellitus. The recently identified neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are hypothalamic small proteins that stimulate food intake and fat accumulation in several animals. To clarify the mechanisms that evoke feeding behavior and induce energy metabolism at the appropriate times in accordance with a circadian rhythm, diurnal fluctuations in Npgl and Npgm mRNA expression were investigated in mice. Quantitative RT-PCR analysis revealed that the mRNAs of these two genes were highly expressed in the mediobasal hypothalamus during the active dark phase under ad libitum feeding. In mice restricted to 3 h of feeding during the inactive light phase, the Npgl mRNA level was augmented in the moment prior to the feeding period and the midnight peak of Npgm mRNA was attenuated. Moreover, the mRNA expression levels of clock genes, feeding regulatory neuropeptides, and lipid metabolic enzymes in the central and peripheral tissues were comparable to those of central Npgl and Npgm. These data suggest that Npgl and Npgm transcription fluctuates daily and likely mediates feeding behavior and/or energy metabolism at an appropriate time according to the meal timing.

Highlights

In many industrialized countries, the health of shift workers has become an issue of concern, given that night shift and rotating shift work are associated with an increased prevalence of various disorders, such as diabetes, cardiovascular disease, and cancer [1,2].The body’s biological clock regulates the sleep/wake cycle, body temperature, metabolism, and hormone secretion, allowing the physiological processes to adapt to the light/dark cycle [3]
We investigated the mRNA expression profiles of four clock genes (Bmal1, Per2, Cry1, and Nr1d1) to examine their rhythmicity and responses to feeding times
We examined the daily mRNA expression profiles of Npgl and Npgm under ad libitum feeding (ALF)

Summary

Introduction

The body’s biological clock regulates the sleep/wake cycle, body temperature, metabolism, and hormone secretion, allowing the physiological processes to adapt to the light/dark cycle [3]. In mammals, these circadian rhythms are controlled through the suprachiasmatic nucleus (SCN), the central region in the hypothalamus that generates neuronal and hormonal activity [4,5,6]. CLOCK and BMAL1 heterodimerize and inhibit their own expression by inducing the transcription of their transcriptional repressors, the Per and Cry genes [10,11,12]. It is known that peripheral tissues, such as liver, skeletal muscle, and adipose tissue, have independent biological rhythms in accordance with the light/dark cycle [7,15]

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