ArticleProceedings of the National Academy of Sciences of the United States of America2023
CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- [Lonicera japonica attenuates oxidative stress and improves post-ischemic heart failure in miceNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Ultrasound-Activatable Piezoelectric Hydrogel Reprograms Mitochondrial Epigenetics for Osteoarthritis Therapy via the mTOR/GATD3A Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanism and therapeutic prospects of adipose tissue B lymphocytes in obesity and obesity‑associated metabolic diseases (Review).Molecular medicine reports · 2026Review
- Saikosaponin D and paeoniflorin improve the HCC immune microenvironment via CLCF1/PD-L1 mediated crosstalk between CAFs and tumor cells.Scientific reports · 2026Article
- The secretory protein, CLCF1, improves cholestatic liver disease by inhibiting hepatic bile acid synthesis and promoting bile acid excretion.Communications biology · 2026Article
- Article
- Latest Advances in Obesity Treatment by Regulating Adipocyte Thermogenesis.PPAR research · 2026Review
- Cardiotrophin-like cytokine factor 1 forms a complex with IL12/IL23p40.Scientific reports · 2025Article
- Mitochondrial Quality Control in Health and Disease.MedComm · 2025Review
- CLCF1 contributes to high-glucose-induced EndMT by modulating JAK2/STAT3 signaling.European journal of medical research · 2025Article
- Advancements in the understanding of mechanisms of the IL-6 family in relation to metabolic-associated fatty liver disease.Frontiers in endocrinology · 2025Review
- Detection of CLCF1 protein expression by flow cytometry.Scientific reports · 2024Article
- The Role of Exerkines in Obesity-Induced Disruption of Mitochondrial Homeostasis in Thermogenic Fat.Metabolites · 2024Review
- The secretory function of adipose tissues in metabolic regulation.Life metabolism · 2024Review
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- CLCF1 signaling restrains thermogenesis and disrupts metabolic homeostasis by inhibiting mitochondrial biogenesis in brown adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1β, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.
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