PMID- 37154385
OWN - NLM
STAT- MEDLINE
DCOM- 20230616
LR  - 20230706
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 601
IP  - 12
DP  - 2023 Jun
TI  - Exercise improves homeostasis of the intestinal epithelium by activation of 
      apelin receptor-AMP-activated protein kinase signalling.
PG  - 2371-2389
LID - 10.1113/JP284552 [doi]
AB  - Intestinal remodelling is dynamically regulated by energy metabolism. Exercise is 
      beneficial for gut health, but the specific mechanisms remain poorly understood. 
      Intestine-specific apelin receptor (APJ) knockdown (KD) and wild-type male mice 
      were randomly divided into two subgroups, with/without exercise, to obtain four 
      groups: WT, WT with exercise, APJ KD and APJ KD with exercise. Animals in the 
      exercise groups were subjected to daily treadmill exercise for 3 weeks. Duodenum 
      was collected at 48 h after the last bout of exercise. AMP-activated protein 
      kinase (AMPK) alpha1 KD and wild-type mice were also utilized for investigating the 
      mediatory role of AMPK on exercise-induced duodenal epithelial development. AMPK 
      and peroxisome proliferator-activated receptor gamma coactivator-1 alpha were upregulated 
      by exercise via APJ activation in the intestinal duodenum. Correspondingly, 
      exercise induced permissive histone modifications in the PR domain containing 16 
      (PRDM16) promoter to activate its expression, which was dependent on APJ 
      activation. In agreement, exercise elevated the expression of mitochondrial 
      oxidative markers. The expression of intestinal epithelial markers was 
      downregulated due to AMPK deficiency, and AMPK signalling facilitated epithelial 
      renewal. These data demonstrate that exercise-induced activation of the APJ-AMPK 
      axis facilitates the homeostasis of the intestinal duodenal epithelium. KEY 
      POINTS: Apelin receptor (APJ) signalling is required for improved epithelial 
      homeostasis of the small intestine in response to exercise. Exercise intervention 
      activates PRDM16 through inducing histone modifications, enhanced mitochondrial 
      biogenesis and fatty acid metabolism in duodenum. The morphological development 
      of duodenal villus and crypt is enhanced by the muscle-derived exerkine apelin 
      through the APJ-AMP-activated protein kinase axis.
CI  - (c) 2023 The Authors. The Journal of Physiology (c) 2023 The Physiological Society.
FAU - Chae, Song Ah
AU  - Chae SA
AD  - Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, 
      Washington State University, Pullman, WA, USA.
FAU - Du, Min
AU  - Du M
AUID- ORCID: 0000-0002-7232-072X
AD  - Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, 
      Washington State University, Pullman, WA, USA.
FAU - Son, Jun Seok
AU  - Son JS
AD  - Laboratory of Perinatal Kinesioepigenetics, Department of Obstetrics, Gynecology 
      & Reproductive Sciences, University of Maryland School of Medicine, Baltimore, 
      MD, USA.
AD  - Department of Physiology, University of Maryland School of Medicine, Baltimore, 
      MD, USA.
FAU - Zhu, Mei-Jun
AU  - Zhu MJ
AUID- ORCID: 0000-0001-8027-1780
AD  - School of Food Science, Washington State University, Pullman, WA, USA.
LA  - eng
GR  - R01 HD067449/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230516
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Apelin Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Mice
MH  - Male
MH  - Animals
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - Apelin Receptors
MH  - *Signal Transduction/physiology
MH  - Transcription Factors/metabolism
MH  - Homeostasis
MH  - Intestinal Mucosa/metabolism
PMC - PMC10280693
MID - NIHMS1898813
OTO - NOTNLM
OT  - AMPK
OT  - APJ
OT  - PRDM16
OT  - duodenum
OT  - exercise
OT  - mitochondrial oxidation
COIS- Competing interests. The authors declare no competing interests.
EDAT- 2023/05/08 13:41
MHDA- 2023/06/16 06:42
PMCR- 2024/06/01
CRDT- 2023/05/08 07:33
PHST- 2023/02/16 00:00 [received]
PHST- 2023/05/05 00:00 [accepted]
PHST- 2024/06/01 00:00 [pmc-release]
PHST- 2023/06/16 06:42 [medline]
PHST- 2023/05/08 13:41 [pubmed]
PHST- 2023/05/08 07:33 [entrez]
AID - 10.1113/JP284552 [doi]
PST - ppublish
SO  - J Physiol. 2023 Jun;601(12):2371-2389. doi: 10.1113/JP284552. Epub 2023 May 16.