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Cited by 24Adipose Tissue and MetabolismCircadian rhythm and melatoninAdipokines, Inflammation, and Metabolic Diseases

Circadian clock control of MRTF/SRF pathway suppresses beige adipocyte thermogenic recruitment

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Xiong, Xuekai, Li, Weini, Liu, Ruya, Saha, Pradip, Yechoor, Vijay, Ma, Ke·2023·Journal of Molecular Cell Biology
DOI 10.1093/jmcb/mjac079PMC PMC10174720

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Abstract

The morphological transformation of adipogenic progenitors into mature adipocytes requires dissolution of actin cytoskeleton with loss of myocardin-related transcription factor (MRTF)/serum response factor (SRF) activity. Circadian clock confers temporal control in adipogenic differentiation, while the actin cytoskeleton–MRTF/SRF signaling transduces extracellular physical niche cues. Here, we define a novel circadian transcriptional control involved in actin cytoskeleton–MRTF/SRF signaling cascade that modulates beige fat thermogenic function. Key components of actin dynamic–MRTF/SRF pathway display circadian regulation in beige fat depot. The core clock regulator, brain and muscle arnt-like 1 (Bmal1), exerts direct transcriptional control of genes within the actin dynamic–MRTF/SRF cascade that impacts actin cytoskeleton organization and SRF activity. Employing beige fat-selective gene-targeting models together with pharmacological rescues, we further demonstrate that Bmal1 inhibits beige adipogenesis and thermogenic capacity in vivo via the MRTF/SRF pathway. Selective ablation of Bmal1 induces beigeing with improved glucose homeostasis, whereas its targeted overexpression attenuates thermogenic induction resulting in obesity. Collectively, our findings identify the clock–MRTF/SRF regulatory axis as an inhibitory mechanism of beige fat thermogenic recruitment with significant contribution to systemic metabolic homeostasis.

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Cited by

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Authors
Xiong, X., Li, W., Liu, R., Saha, P., Yechoor, V., & Ma, K.
Affiliations
  • City Of Hope National Medical Center (US)
  • University of Pittsburgh (US)
  • Baylor College of Medicine (US)
Corresponding author
Ma, Ke
ORCID
Venue
Journal of Molecular Cell Biology
Publisher
Oxford University Press (OUP)
Published
2022-12
Volume
14
Issue
12
ISSN
  • 1674-2788 (ISSN-L)
  • 1759-4685
DOI
10.1093/jmcb/mjac079
PMC
PMC10174720
OpenAlex
W4313312171
Cited by
24
References
1
Citations by year
2026: 9 · 2025: 6 · 2024: 3 · 2023: 6
FWCI
2.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Cell Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • National Institutes of Health (1R01DK112794, DK097160-01, 1R01DK130499)
  • American Heart Association (17GRNT33370012)
Topics
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
circadian clock, Bmal1, beige adipocytes, thermogenesis, actin cytoskeleton, adipogenesis, adipose tissue browning, glucose homeostasis, obesity
MeSH terms
Adipocytes, Beige, Myocardin, Actins, Animals, Trans-Activators, Thermogenesis, Serum Response Factor, Mice, ARNTL Transcription Factors, Circadian Clocks

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