ArticleThe Journal of clinical investigation2021
LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Investigating the Role ofJournal of clinical research in pediatric endocrinology · 2026Article
- Circulating immunometabolic signatures of sarcopenia at high altitude.The journal of nutrition, health & aging · 2026Article
- Immunometabolic Dysregulation in Obesity: Integrating Macrophage Polarization, Metabolic Reprogramming, and Gut Microbiota Crosstalk.Immunity, inflammation and disease · 2026Review
- Cell-type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.Cell reports · 2026Article
- Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.Cellular & molecular immunology · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Advances in Adipose Tissue Biology.Endocrine reviews · 2026Review
- Cell type-specific proximity labeling of organ secretomes reveals energy balance-dependent proteomic remodeling.bioRxiv : the preprint server for biology · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Circulating spexin and adiponectin as early biomarkers of insulin resistance in pediatric obesity.BMC endocrine disorders · 2026Article
- Intermittent fasting ameliorates MAFLD by downregulating Lrg1: insights from bulk RNA sequencing and functional verification.Frontiers in endocrinology · 2026Article
- Adipokine in Metabolic Liver Disease: Adipo-Brain-Liver Cross talk.International journal of endocrinology · 2026Review
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Recent advances in reprogramming lactate metabolism in polycystic ovary syndrome.Journal of ovarian research · 2025Review
- Leucine-rich alpha-2-glycoprotein 1 (LRG1) decrement during biologics therapy and its correlation with disease features and treatment outcomes in rheumatoid arthritis patients.Clinical rheumatology · 2025Article
- The Change of Noncoding RNA Expression in Olfactory Bulb of Hepatic Encephalopathy Mouse Model: Transcriptomic Analysis and Cellular Analysis.CNS neuroscience & therapeutics · 2025Article
- The Role of Obesity in the Regulation of Immunosuppressive Cell Infiltration and Immunosurveillance in Cancers.Diseases (Basel, Switzerland) · 2025Review
- Article
- Diet-enhanced LRG1 expression promotes insulin hypersecretion and ER stress in pancreatic beta cells.Diabetologia · 2025Article
- Mechanism-guided pharmacotherapy for cardiometabolic multimorbidity: from pathophysiology to phenotype-prioritized treatment.Frontiers in endocrinology · 2025Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet-induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.
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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.