ArticleNature metabolism2022
Histone deacetylase 6 inhibition restores leptin sensitivity and reduces obesity.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Secretion Patterns of Leptin: A Key Component in the Regulation of Energy Homeostasis and Its Therapeutic Applications.Biomolecules · 2026Review
- Identification of a mechanism-based binding mode for a histone deacetylase 6 inhibitor.Nature communications · 2026Article
- Targeting hypothalamic SIK3 to promote weight loss and improve glycemic control in mice.Nature communications · 2026Article
- Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors.ACS pharmacology & translational science · 2026Review
- Modulation and Reprogramming of Adipose Tissue Macrophages in Obesity.Biomolecules · 2026Review
- Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.Journal of translational medicine · 2026Review
- The focal adhesion kinases regulate leptin action and the weight reducing effect of HDAC6 inhibition.Nature communications · 2026Article
- Recent Insights Into Circulating Adipokines in Obesity: Systematic Review and Meta-Analysis.Obesity science & practice · 2026Review
- A small molecule PTER-selective inhibitor reduces food intake and body weight.bioRxiv : the preprint server for biology · 2026Article
- Restoring leptin sensitivity in metabolic and extra-metabolic leptin resistance: Pharmacologic strategies, systemic implications, and future directions.EXCLI journal · 2026Review
- Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions.Military Medical Research · 2026Review
- Decoding the Adipocyte Epigenome: Differentiation, Metabolic Memory, and Obesity.Journal of obesity & metabolic syndrome · 2025Review
- Epigenetic Changes Associated With Obesity-related Metabolic Comorbidities.Journal of the Endocrine Society · 2025Review
- Gut Microbiota as a Mediator Between Intestinal Fibrosis and Creeping Fat in Crohn's Disease.United European gastroenterology journal · 2025Review
- Leptin and leptin resistance in obesity: current evidence, mechanisms and future directions.Endocrine connections · 2025Review
- Review
- Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Epigenetic Mechanisms of Obesity: Insights from Transgenic Animal Models.Life (Basel, Switzerland) · 2025Review
- Butyrate Prevents Obesity Accompanied by HDAC9-Mediated Browning of White Adipose Tissue.Biomedicines · 2025Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The adipose tissue-derived hormone leptin can drive decreases in food intake while increasing energy expenditure. In diet-induced obesity, circulating leptin levels rise proportionally to adiposity. Despite this hyperleptinemia, rodents and humans with obesity maintain increased adiposity and are resistant to leptin's actions. Here we show that inhibitors of the cytosolic enzyme histone deacetylase 6 (HDAC6) act as potent leptin sensitizers and anti-obesity agents in diet-induced obese mice. Specifically, HDAC6 inhibitors, such as tubastatin A, reduce food intake, fat mass, hepatic steatosis and improve systemic glucose homeostasis in an HDAC6-dependent manner. Mechanistically, peripheral, but not central, inhibition of HDAC6 confers central leptin sensitivity. Additionally, the anti-obesity effect of tubastatin A is attenuated in animals with a defective central leptin-melanocortin circuitry, including db/db and MC4R knockout mice. Our results suggest the existence of an HDAC6-regulated adipokine that serves as a leptin-sensitizing agent and reveals HDAC6 as a potential target for the treatment of obesity.
Indexed as
Identifiers
What OpenQuestion holds
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.