Epac1 mediates thermogenesis and lipolysis in white adipose tissue via the p38γ-NFAT5 axis in a PKA-independent manner
Wang B., Chen CY., Liu J., Wang Q., Zhang W., Liu J.
Animal Study, published in Clin Sci (Lond) (2025) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Clin Sci (Lond) (2025)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 40411181
- PMCID
- PMC12238815
- DOI
- 10.1042/cs20256710
- Citations
- 1
Abstract (original English)
Beige adipocytes in white adipose tissue (WAT) share similar functions as brown adipocytes by converting lipids into heat through thermogenesis, while lipolysis is considered as a prerequisite for the activation of non-shivering thermogenesis. β3-adrenergic receptor (β3-AR) agonist CL316,243 (CL) and cold exposure are known to enhance lipolysis and beiging of WAT in a protein kinase A (PKA)-dependent manner, while the role of PKA-independent pathways involved is still poorly understood. Here, we show that the exchange protein directly activated by cAMP 1 (Epac1), a downstream target of cAMP, mediates β3-AR activation to modulate thermogenesis and lipolysis in a PKA-independent manner. Upon CL treatment or cold exposure, both thermogenic and lipolytic responses were compromised in Epac1-deficient mice, as evidenced by reduced oxygen consumption, less beige adipocytes, lower body temperature, and decreased circulating glycerol. Additionally, in vitro beige adipogenesis with or without cAMP analog treatment was significantly impaired in Epac1-deficient mice. Mechanistically, reduced total and phosphorylated p38γ and decreased induction of nuclear factor activated in T cells 5 (NFAT5) were observed in Epac1-deficient mice, which may contribute to the defective beiging of WAT. However, WAT of wildtype and Epac1-deficient mice showed no significant induction difference in phosphoryla
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
How we grade evidenceBrowse all related research
Filter the research library by this study's title keywords, author, or publication year.