Effects of feeding time on daily rhythms of neuropeptide and clock gene expression in the rat hypothalamus

Jul 16, 2017Brain research

How Meal Timing Affects Daily Patterns of Brain Chemicals and Internal Clocks in Rats’ Hypothalamus

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Abstract

Feeding at night disrupts the expression of clock genes in the hypothalamus.

Hypothalamic nuclei show diurnal variation in clock gene expression when food is available at all times.
Clock gene rhythms are lost when food is restricted to the light period.
Neuropeptide genes related to energy metabolism exhibit limited daily variation, with orexin-receptor 1 showing some variation in animals with constant food access.
No significant diurnal variation is observed in genes related to glutamatergic and GABAergic signaling regardless of feeding time.
Disruption of feeding timing may lead to desynchronization between brain and body clocks and within the hypothalamus.

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Shiftworkers are exposed to several adverse health conditions, one being eating at night. Food consumption at an unnatural time-of-day is thought to be one of the main factors responsible for the increased risk of developing metabolic diseases, such as obesity and diabetes mellitus. The underlying mechanism is considered to include disruption of the circadian organization of physiology, leading to disruption of metabolism. When food is consumed at night, the hypothalamus, a brain region central to homeostasis, receives contradicting input from the central clock and the systemic circulation. This study investigated how timing of feeding affects hypothalamic function by studying, in different hypothalamic nuclei, expression of clock genes and key neuropeptide genes involved in energy metabolism, including orexin, melanin-concentrating hormone (MCH) and neuropeptide Y. Animals with food available ad libitum showed diurnal variation in the expression of clock genes Per1 and Per2 in the perifornical area and arcuate nucleus. Clock gene rhythms were lost in both nuclei when food was restricted to the light (i.e., sleep) period. Neuropeptide genes did not display significant daily variation in either feeding groups, except for orexin-receptor 1 in ad libitum animals. Analysis of genes involved in glutamatergic and GABAergic signaling did not reveal diurnal variation in expression, nor effects of feeding time. In conclusion, feeding at the 'wrong' time-of-day not only induces desynchronization between brain and body clocks but also within the hypothalamus, which may contribute further to the underlying pathology of metabolic dysregulation.

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Effects of feeding time on daily rhythms of neuropeptide and clock gene expression in the rat hypothalamus

Abstract

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