Time-Restricted Eating: Benefits, Mechanisms, and Challenges in Translation

Prashant Regmi, Leonie K Heilbronn, Prashant Regmi, Leonie K Heilbronn

Abstract

Eating out of phase with daily circadian rhythms induces metabolic desynchrony in peripheral metabolic organs and may increase chronic disease risk. Time-restricted eating (TRE) is a dietary approach that consolidates all calorie intake to 6- to 10-h periods during the active phase of the day, without necessarily altering diet quality and quantity. TRE reduces body weight, improves glucose tolerance, protects from hepatosteatosis, increases metabolic flexibility, reduces atherogenic lipids and blood pressure, and improves gut function and cardiometabolic health in preclinical studies. This review discusses the importance of meal timing on the circadian system, the metabolic health benefits of TRE in preclinical models and humans, the possible mechanisms of action, the challenges we face in implementing TRE in humans, and the possible consequences of delaying initiation of TRE.

Keywords: Biological Sciences; Chronobiology; Nutrition.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1
Figure 1
TRE Metabolic Benefits
Figure 2
Figure 2
TRE Regulation of Peripheral Circadian Clocks TRE can reprogram circadian clock in the fasting state via AMPK and in the fed state via mTOR. (A) In the fed state, nutrient availability activates mTOR. Activated mTOR induces Cry, which represses Clock:Bmal1. (B) In the fasting state, nutrient depletion activates AMPK that directly and indirectly enhances phosphorylation on cry, and per. Phosphorylation is key for degradation of these proteins. Next, AMPK can activate SIRT1 activity via NAMPT. SIRT1 binds with clock:bmal1 and represses the transcription of per2. The acetyltransferase activity of clock is counteracted by SIRT1. Blue arrows represent core clock machinery, green arrows represent effect of TRE. AMPK:,AMP-activated protein kinase; bmal1, brain and muscle arnt like 1; CCG, clock-controlled genes; CK, casein kinase; clock, circadian locomotor output cycle kaput; cry, cryptochrome; mTOR, mechanistic target of rapamycin; NAD, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyl transferase; per, period; SIRT1, sirtuin1.

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