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Cell Metab. 2017 Dec 5;26(6):856-871.e5. doi: 10.1016/j.cmet.2017.09.020. Epub 2017 Oct 26.

System-wide Benefits of Intermeal Fasting by Autophagy.

Author information

1
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA.
3
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
4
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA; Department of Neurology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5
Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.
6
Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: rajat.singh@einstein.yu.edu.

Abstract

Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin. ITAD feeding decreases adiposity and, unlike CR, enhances muscle mass. ITAD feeding drives energy expenditure, lowers lipid levels, suppresses gluconeogenesis, and prevents age/obesity-associated metabolic defects. Using liver-, adipose-, myogenic-, and proopiomelanocortin neuron-specific autophagy-null mice, we mapped the contribution of tissue-specific autophagy to system-wide benefits of ITAD feeding. Our studies suggest that consuming two meals a day without CR could prevent the metabolic syndrome.

KEYWORDS:

POMC; aging; autophagy; caloric restriction; circadian; fatty liver; gluconeogenesis; metabolic syndrome; myogenic progenitors; twice-a-day feeding

Comment in

PMID:
29107505
PMCID:
PMC5718973
DOI:
10.1016/j.cmet.2017.09.020
[Indexed for MEDLINE]
Free PMC Article

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