Meal timing and energy restriction as regulators of central and peripheral human rhythms
Lead Research Organisation:
University of Surrey
Department Name: Biochemistry & Physiology
Abstract
Most living organisms possess internal biological clocks that regulate daily (circadian) rhythms in many key physiological functions (e.g. hormone secretion, sleep time, metabolism). The circadian timing system in mammals, including humans, consists of a 'master' clock within a part of the brain called the hypothalamus and many 'peripheral' clocks found throughout the body (e.g. in liver, pancreas and fat tissue). There is increasing evidence to show that many of these clocks play an important role in timing our metabolism, including how we respond to meals eaten at different times of day. This work is extremely important as it is beginning to explain how meal timing (not just food type and quantity) influences our body weight and long-term health.
For our internal clocks to be matched to external changes in the environment, they are synchronised by various environmental time cues. Although it is known that the light/dark cycle is the main synchroniser of the 'master' clock in the brain, other signals are important for synchronising clocks throughout the body. The time of feeding is an important signal for synchronising peripheral clocks in animals. We have recently shown for the first time that some human rhythms (e.g. of glucose concentration) are synchronised by meal timing and can even anticipate regular large meals. The condition of negative energy balance (consuming less energy than is needed for the body's basic metabolic needs) also shifts the 'master' clock in the brain of rodents. However, major unanswered questions include: 1) which meal provides the main synchronising signal in humans, and 2) how does negative energy balance affect the influence of meal timing on human circadian biology.
These questions are important as they will enable us to design effective meal timing strategies to best help the millions of people who are subject to disorders caused by a disorganised circadian system. Such individuals include shift workers, people experiencing jet-lag and the blind.
Very few places in the world can perform well-controlled human circadian experiments. At the University of Surrey, we have the benefit of world leading human clinical facilities, plus experts in circadian rhythms and nutritional science. Through our recent research, we have become world leaders in the field of chrono-nutrition (effect of meal timing) and the analysis of metabolite rhythms in samples from human volunteers using state-of-the-art technology called metabolomics. We therefore propose to build upon our recent successes by conducting extremely timely experiments to enhance our understanding of how meal timing can regulate human circadian rhythms and metabolic physiology.
The results of the work will have important implications for scientists and the public. Scientists will learn crucial new information about the basic biology of body clocks and how they are regulated by food timing and energy balance. Our work will provide a major boost to the design of novel dietary interventions to reduce the burden of shift work and jet lag on adverse health consequences (obesity, Type 2 diabetes, cardiovascular disease). Our recent research has received extensive media and public interest, so results from this project are highly likely to be of broad interest. In particular, we hope to discover new scientific findings that will underpin the use of timed meal approaches to treat sufferers of circadian disorders including air travellers, shift workers and the totally blind.
For our internal clocks to be matched to external changes in the environment, they are synchronised by various environmental time cues. Although it is known that the light/dark cycle is the main synchroniser of the 'master' clock in the brain, other signals are important for synchronising clocks throughout the body. The time of feeding is an important signal for synchronising peripheral clocks in animals. We have recently shown for the first time that some human rhythms (e.g. of glucose concentration) are synchronised by meal timing and can even anticipate regular large meals. The condition of negative energy balance (consuming less energy than is needed for the body's basic metabolic needs) also shifts the 'master' clock in the brain of rodents. However, major unanswered questions include: 1) which meal provides the main synchronising signal in humans, and 2) how does negative energy balance affect the influence of meal timing on human circadian biology.
These questions are important as they will enable us to design effective meal timing strategies to best help the millions of people who are subject to disorders caused by a disorganised circadian system. Such individuals include shift workers, people experiencing jet-lag and the blind.
Very few places in the world can perform well-controlled human circadian experiments. At the University of Surrey, we have the benefit of world leading human clinical facilities, plus experts in circadian rhythms and nutritional science. Through our recent research, we have become world leaders in the field of chrono-nutrition (effect of meal timing) and the analysis of metabolite rhythms in samples from human volunteers using state-of-the-art technology called metabolomics. We therefore propose to build upon our recent successes by conducting extremely timely experiments to enhance our understanding of how meal timing can regulate human circadian rhythms and metabolic physiology.
The results of the work will have important implications for scientists and the public. Scientists will learn crucial new information about the basic biology of body clocks and how they are regulated by food timing and energy balance. Our work will provide a major boost to the design of novel dietary interventions to reduce the burden of shift work and jet lag on adverse health consequences (obesity, Type 2 diabetes, cardiovascular disease). Our recent research has received extensive media and public interest, so results from this project are highly likely to be of broad interest. In particular, we hope to discover new scientific findings that will underpin the use of timed meal approaches to treat sufferers of circadian disorders including air travellers, shift workers and the totally blind.
Technical Summary
The mammalian circadian timing system consists of a master/central clock in the hypothalamic suprachiasmatic nuclei (SCN) and many other peripheral clocks throughout the body. The light/dark cycle is the predominant time cue (zeitgeber) for entrainment of the SCN, which then synchronises the peripheral clocks via various mechanisms including neuronal and endocrine signals, plus the timing of sleep-wake and feeding-fasting behavioural cycles.
Timed feeding is a major synchronising signal for animal peripheral clocks. Negative energy balance also shifts the SCN clock of rodents. We have recently shown for the first time that some human rhythms (e.g. of glucose concentration) are synchronised by meal timing and can even anticipate regular large meals. However, major unanswered questions include: 1) which meal (considering time and prior fasting duration) provides the main synchronising signal in humans, and 2) how does negative energy balance effect the influence of meal timing on human SCN clock and other circadian rhythms.
In this study, we will conduct two key experiments. In experiment 1, we will test the hypothesis that, in a state of energy balance, glucose rhythms and most of the circadian metabolites synchronise to the meal occurring after the longest fasting period, while melatonin rhythms (a biomarker of the SCN clock) synchronise to the light-dark cycle. In experiment 2, we will test the hypothesis that melatonin rhythms (as a marker of the SCN clock), glucose rhythms and all circadian plasma metabolites will synchronise to meal timing in a state of negative energy balance.
These experiments will provide a timely and high impact addition to the fields of chronobiology and nutrition/metabolism. The research will provide new scientific findings that will underpin meal timing strategies for sufferers of circadian disorders including air travellers, shift workers and the totally blind.
Timed feeding is a major synchronising signal for animal peripheral clocks. Negative energy balance also shifts the SCN clock of rodents. We have recently shown for the first time that some human rhythms (e.g. of glucose concentration) are synchronised by meal timing and can even anticipate regular large meals. However, major unanswered questions include: 1) which meal (considering time and prior fasting duration) provides the main synchronising signal in humans, and 2) how does negative energy balance effect the influence of meal timing on human SCN clock and other circadian rhythms.
In this study, we will conduct two key experiments. In experiment 1, we will test the hypothesis that, in a state of energy balance, glucose rhythms and most of the circadian metabolites synchronise to the meal occurring after the longest fasting period, while melatonin rhythms (a biomarker of the SCN clock) synchronise to the light-dark cycle. In experiment 2, we will test the hypothesis that melatonin rhythms (as a marker of the SCN clock), glucose rhythms and all circadian plasma metabolites will synchronise to meal timing in a state of negative energy balance.
These experiments will provide a timely and high impact addition to the fields of chronobiology and nutrition/metabolism. The research will provide new scientific findings that will underpin meal timing strategies for sufferers of circadian disorders including air travellers, shift workers and the totally blind.
