• Nutrition · Sep 2022

    Randomized Controlled Trial

    Intermittent fasting activates markers of autophagy in mouse liver, but not muscle from mouse or humans.

    • Rajesh Chaudhary, Bo Liu, Julien Bensalem, Timothy J Sargeant, Amanda J Page, Gary A Wittert, Amy T Hutchison, and Leonie K Heilbronn.
    • Adelaide Medical School, The University of Adelaide, Adelaide, South Australia; Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
    • Nutrition. 2022 Sep 1; 101: 111662.

    ObjectivesIntermittent fasting (IF) activates autophagy in cardiac muscle and pancreatic islets. We examined the effect of IF on markers of autophagy in liver and skeletal muscle in mice and in humans.MethodsTen-wk-old C57 BL/6 J male mice were ad libitum (AL) fed a high-fat diet (HFD) or chow diet for 8 wk, before randomization to AL or IF (24-h fast, 3 non-consecutive days per week) for 8 wk (8-16 per group). Tissue was collected in the fed or 22-h fasted state. Fifty women (51 ± 2 y, 31.8 ± 4.3 kg/m2) were randomly assigned to one of two IF protocols (24-hfast, 3 non-consecutive days per week) and fed at 70% (IF70) or 100% (IF100) of energy requirements for 8 wk. Vastus lateralis muscle was collected at 0800 after 12- and 24-h fasts. Microtubule-associated protein light chain 1 (Map1 lc3 b), Beclin1 (Becn1), Sequestosome 1 (Sqstm1/p62), and Lysosomal associated membrane protein 2 (Lamp2) were assessed by quantitative polymerase chain reaction and LC3, BECLIN1 and LAMP1 protein content by immunoblotting.ResultsFasting increased hepatic LC3 I protein and Map1 lc3 b mRNA levels in IF mice fed chow or HFD. LAMP1 protein and Beclin1 mRNA levels in liver were also increased by fasting, but only in chow-fed mice. IF did not activate markers of autophagy in mouse muscle. In humans, a 24-h fast increased SQSTM1. BECLIN1, SQSTM1 and LAMP2 mRNA levels were decreased in IF70 after a 12-h overnight fast .ConclusionMarkers of autophagy in liver, but not in muscle, were elevated in response to IF in mice. In humans, autophagy markers in muscle were reduced, likely in response to weight loss.Copyright © 2022 Elsevier Inc. All rights reserved.

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