Journal Article

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

Bensalem, Julien, Liu, Bo, Heilbronn, Leonie K., Hutchison, Amy T., Wittert, Gary A., Chaudhary, Rajesh, Sargeant, Timothy J., Page, Amanda J.

2022

Overview

•In this study, the effect of intermittent fasting on tissue-specific autophagy was examined in humans and mice.•Fasting transiently increased markers of autophagy in liver, but not skeletal muscle, in intermittent fasting mice that were fed chow or high-fat diet. However, diet-induced obese mice displayed impaired ability to alter autophagy including lysosomal function.•Fasting also did not alter markers of autophagy at the mRNA level in skeletal muscle of humans. However, reductions in markers of autophagy were noted on non-fasting days, potentially indicating a positive effect of weight loss. Intermittent 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. Ten-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. Fasting 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 . Markers 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.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Animals / Autophagy / Body mass index / Body weight loss / Cardiac muscle / Diet / Energy / Energy requirements / Fasting / Food / Gene expression / Glucose / High fat diet / Immunoblotting / Insulin / Intermittent fasting / Liver / males / Markers / Membrane proteins / Metabolism / mice / microtubules / mRNA / Muscles / Musculoskeletal system / myocardium / Obesity / Polymerase chain reaction / Proteins / Quadriceps muscle / Skeletal muscle / Weight loss