ArticleCell metabolism2023
Metformin triggers a kidney GDF15-dependent area postrema axis to regulate food intake and body weight.
Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Metformin and Weight Changes in Non-diabetic Older People With HIV (METFORAGING): A Double-Blind, Randomized, Placebo-Controlled, Pilot Trial.Open forum infectious diseases · 2026Trial
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- Effects of a two-week modified ketogenic diet on circulating lipoprotein subclasses, GDF15, and FGF21 in obese adults.Journal of translational medicine · 2025Trial
- GDF-15 levels in patients with polycystic ovary syndrome treated with metformin: a combined clinical and in silico pathway analysis.Archives of endocrinology and metabolism · 2024Trial
- Lipid sensing and brain hormone receptors in food intake and glucose regulation.Nature reviews. Endocrinology · 2026Review
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- Growth Differentiation Factor-15 in Diabetic Kidney and Cardiovascular Disease: Pathogenic Driver or Protective Modulator.Diabetes · 2026Review
- Combined impact of microalbuminuria and obesity on cardiovascular outcomes in hospitalized heart failure patients: a cohort study.BMC cardiovascular disorders · 2026Observational
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
- GDF15 Improves Renal Injury Induced by Ectopic Lipid Deposition via AMPK/SIRT1 Pathway-Mediated Autophagy.Metabolites · 2026Article
- Article
- PPARβ/δ contributes to the antidiabetic effect and the increase in GDF15 caused by metformin.Acta pharmacologica Sinica · 2026Article
- Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- 1,1-Diethoxyethane increases insulin sensitivity and ameliorates obesity and dyslipidemia in mice fed high-fat diet.npj metabolic health and disease · 2026Article
- Hepatic mitochondrial signaling as a systemic hub: inter-organ communication networks in aging and aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- GDF15 as a sentinel of metabolic integrity: a narrative review of stress signaling, multisystem pathophysiology, and therapeutic potential.Frontiers in endocrinology · 2026Review
- Sex Differences in Albuminuria Risk with Metformin Use: Insights from a Cross-Sectional Study and Drug-Target Mendelian Randomization Analysis.Diabetes & metabolism journal · 2025Article
- Article
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12 authors at 4 institutions in 3 countries.
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Abstract
Metformin, the most widely prescribed medication for obesity-associated type 2 diabetes (T2D), lowers plasma glucose levels, food intake, and body weight in rodents and humans, but the mechanistic site(s) of action remain elusive. Metformin increases plasma growth/differentiation factor 15 (GDF15) levels to regulate energy balance, while GDF15 administration activates GDNF family receptor α-like (GFRAL) that is highly expressed in the area postrema (AP) and the nucleus of the solitary tract (NTS) of the hindbrain to lower food intake and body weight. However, the tissue-specific contribution of plasma GDF15 levels after metformin treatment is still under debate. Here, we found that metformin increased plasma GDF15 levels in high-fat (HF) fed male rats through the upregulation of GDF15 synthesis in the kidney. Importantly, the kidney-specific knockdown of GDF15 expression as well as the AP-specific knockdown of GFRAL expression negated the ability of metformin to lower food intake and body weight gain. Taken together, we unveil the kidney as a target of metformin to regulate energy homeostasis through a kidney GDF15-dependent AP axis.
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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.