ArticleNature communications2024
Glucocorticoids increase adiposity by stimulating Krüppel-like factor 9 expression in macrophages.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Article
- Glucocorticoid resistance-induced inflammation drives cardiovascular-kidney-metabolic (CKM) syndrome pathophysiology.Trends in endocrinology and metabolism: TEM · 2026Review
- Enalaprilat reverses neutrophil polarization imbalance via targeting taurine-STING axis for treatment of diabetic wounds.Cell reports. Medicine · 2026Article
- Luminespib protects against dexamethasone-induced hepatic, vascular, and metabolic abnormalities in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Identification and characterization of MARCO-expressing tumor-associated macrophages in pancreatic ductal adenocarcinoma with pan-cancer relevance.NPJ precision oncology · 2026Article
- Macrophage Niche Reconstitution Reveals Dynamic Transcriptional and Communication Networks Renal Macrophage-Epithelial Communication.Research square · 2026Article
- The roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.Military Medical Research · 2026Review
- ATG5 Plays a Role inTransboundary and emerging diseases · 2026Article
- Article
- Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)-Induced Polycystic Ovary Syndrome via Liver-Ovary Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glucocorticoid receptor epigenetic activity in the heart.Epigenetics · 2025Review
- Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.Cartilage · 2025Article
- DNA methylation reshapes the expression of adipokines and adipose factors in white adipose tissues.Epigenetics & chromatin · 2025Review
- Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head.Journal of traditional and complementary medicine · 2025Article
- Klf9 Loss of Function Protects Against Glucocorticoids Induced Skeletal Muscle Wasting.Journal of cachexia, sarcopenia and muscle · 2025Article
- Klf9 promotes the repair of myocardial infarction by regulating macrophage recruitment and polarization.JCI insight · 2025Article
- The blood transcriptome of musk deer under heat stress condition reveals the regulatory mechanism of genes to maintain homeostasis metabolism.BMC genomics · 2025Article
- KLF9 in cancer: a potential prognostic marker and therapeutic target.Frontiers in oncology · 2025Review
- Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins.Journal of endocrinological investigation · 2024Review
- Interleukin-6: An Under-Appreciated Inducer of Thermogenic Adipocyte Differentiation.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The mechanisms underlying glucocorticoid (GC)-induced obesity are poorly understood. Macrophages are the primary targets by which GCs exert pharmacological effects and perform critical functions in adipose tissue homeostasis. Here, we show that macrophages are essential for GC-induced obesity. Dexamethasone (Dex) strongly induced Krüppel-like factor 9 (Klf9) expression in macrophages. Similar to Dex, lentivirus-mediated Klf9 overexpression inhibits M1 and M2a markers expression, causing macrophage deactivation. Furthermore, the myeloid-specific Klf9 transgene promotes obesity. Conversely, myeloid-specific Klf9-knockout (mKlf9KO) mice are lean. Moreover, myeloid Klf9 knockout largely blocks obesity induced by chronic GC treatment. Mechanistically, GC-inducible KLF9 recruits the SIN3A/HDAC complex to the promoter regions of Il6, Ptgs2, Il10, Arg1, and Chil3 to inhibit their expression, subsequently reducing thermogenesis and increasing lipid accumulation by inhibiting STAT3 signaling in adipocytes. Thus, KLF9 in macrophages integrates the beneficial anti-inflammatory and adverse metabolic effects of GCs and represents a potential target for therapeutic interventions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.