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Effect of repeated bouts of fasting and refeeding on body composition and proteolysis gene expression in skeletal muscles and liver of C57BL/6J mice

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Abstract

Fasting improves metabolic health, but rapid weight gain after fasting might have a negative impact on health. We investigated whether repeated bouts of fasting and refeeding promote accumulation of body fat and protect skeletal muscle as well as liver from wasting during the subsequent exposure to fasting. We compared changes in body composition after the first bout (bout 1) and the eighth bout (bout 8) of 2-day fasting followed by 5-day re-feeding in 22-week-old C57BL/6J male mice. We have also assessed serum IGF-1 and gene expression of proteasome (MurF1, Atrogin-1) and autophagy (p62, LC3b) markers of protein breakdown in skeletal muscles and liver. In contradiction to our expectations, weight- and aged-matched mice showed slightly greater weight loss in bout 8 compared bout 1 of fasting (17.6 ± 2.2 vs. 15.2 ± 2.4 %, n = 10, p < 0.05). Skeletal muscles showed significant upregulation of proteasome and autophagy markers, but only small loss of mass. Liver wasting was significant even though upregulation of autophagy gene expression was modest compared to skeletal muscles. Serum IGF-1 increased and was associated with significant increase in mass of gonadal white adipose tissue. In summary, repeated bouts of fasting and refeeding lead to high serum IGF-1 levels and promote accumulation of body fat, but does not protect from loss of lean body mass during fasting.

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Abbreviations

CON:

control before fasting

FAST:

fasted

REF:

refed

Bout 1:

first bout of fasting end refeeding

Bout 8:

eighth bout of fasting and refeeding

GAST:

gastrocnemius

PLN:

plantaris

SOL:

soleus

TA:

tibialis anterior

EDL:

extensor digitorum longus

TMB:

tetramethylbenzidine

gWAT:

gonadal white adipose tissue

iBAT:

interscapular brown adipose tissue

IGF-1:

insulin like growth factor 1

FoxO:

forkhead family of transcription factors

MurF1:

muscle RING-finger protein-1

p62:

the sequestosome 1 (SQSTM1) gene that is located on 5q35 and encodes p62 protein

LC3B:

Microtubule-associated protein 1 light chain 3 beta

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Correspondence to Edgaras Lapinskas.

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The study was carried in accordance with the “European convention for the protection of vertebrates used for experimental and other scientific purposes” at the animal research facility of the Lithuanian Sports University after receiving approval of all the procedures by the Lithuanian Republic Alimentary and Veterinary Public Office (Nr. G2-90, 2018).

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Lapinskas, E., Krusnauskas, R. & Ratkevicius, A. Effect of repeated bouts of fasting and refeeding on body composition and proteolysis gene expression in skeletal muscles and liver of C57BL/6J mice. Biologia 76, 3501–3510 (2021). https://doi.org/10.1007/s11756-021-00873-z

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  • DOI: https://doi.org/10.1007/s11756-021-00873-z

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