ArticleScientific reports2024
Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction.
Article in Scientific reports, 2024. 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.
- ASK1-Induced FGF21 Synthesis in the Liver Prevents Obesity in Mice.Obesity (Silver Spring, Md.) · 2026Article
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- Growth differentiation factor 15 mitigates lipotoxic steatosis by preserving mitochondrial morphodynamics and augmenting fatty acid oxidation in hepatocytes and liver organoids.Diabetes, obesity & metabolism · 2026Article
- The impact of bariatric and metabolic surgery on the levels of circulating growth differentiation factor 15 in humans.Journal of physiology and biochemistry · 2026Review
- Selective β3-adrenoceptor agonist reduces energy intake and elevates GDF15 levels in lean and diet-induced obese mice.Endocrine journal · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- GDF15 Is Elevated in Eating Disorders and Is Involved in the Gut-Brain Axis via Ghrelin.European eating disorders review : the journal of the Eating Disorders Association · 2026Article
- Growth Differentiation Factor 15 (GDF-15) as a modulator of hepatic steatosis and fibrosis: insights from a 6-year retrospective cohort study.Frontiers in medicine · 2026Article
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Artificial intelligence as a ploy to delve into the intricate link between genetics and mitochondria in patients with MASLD.JHEP reports : innovation in hepatology · 2025Article
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Pharmacological but Not Physiological Levels of GDF15 and FGF21 Regulate Body Weight and Glycemic Control in Obese Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Adipokine and Hepatokines in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Current and Developing Trends.Biomedicines · 2025Article
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21.Science advances · 2025Article
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
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15 authors.
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Abstract
GDF15 and FGF21, stress-responsive cytokines primarily secreted from the liver, are promising therapeutic targets for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the interaction between GDF15 and FGF21 remains unclear. We examined the effects of hepatocyte-specific GDF15 or FGF21 overexpression in high-fat diet (HFD)-fed mice for 8 weeks. Hydrodynamic injection of GDF15 or FGF21 sustained high circulating levels of GDF15 or FGF21, respectively, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and hepatic steatosis. In addition, GDF15 treatment led to early reduction in body weight despite no change in food intake, indicating the role of GDF15 other than appetite loss. GDF15 treatment increased liver-derived serum FGF21 levels, whereas FGF21 treatment did not affect GDF15 expression. GDF15 promoted eIF2α phosphorylation and XBP1 splicing, leading to FGF21 induction. In murine AML12 hepatocytes treated with free fatty acids (FFAs), GDF15 overexpression upregulated Fgf21 mRNA levels and promoted eIF2α phosphorylation and XBP1 splicing. Overall, continuous exposure to excess FFAs resulted in a gradual increase of β-oxidation-derived reactive oxygen species and endoplasmic reticulum stress, suggesting that GDF15 enhanced this pathway and induced FGF21 expression. GDF15- and FGF21-related crosstalk is an important pathway for the treatment of MASLD.
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