ArticleScience signaling2023
A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity.
Article in Science signaling, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- A scalable framework for identifying allelic series from summary statistics.American journal of human genetics · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- PPARɑ variant V227A reduces plasma triglycerides through enhanced lipoprotein lipolysis.Journal of lipid research · 2025Article
- Microglial ER stress response via IRE1α regulates diet-induced metabolic imbalance and obesity in mice.Molecular metabolism · 2025Article
- Liver gene expression and its rewiring in hepatic steatosis are controlled by PI3Kα-dependent hepatocyte signaling.PLoS biology · 2025Article
- Inhalation exposure to airborne PMAmerican journal of physiology. Cell physiology · 2025Article
- Cgref1 is a CREB-H-regulated hepatokine that promotes hepaticInternational journal of biological sciences · 2025Article
- 2025: The year in cardiovascular disease - the year of triglyceride lowering therapies. Can we effectively reduce triglyceride-related residual cardiovascular disease and pancreatitis risk?Archives of medical science : AMS · 2025Article
- ER-tethered stress sensor CREBH regulates mitochondrial unfolded protein response to maintain energy homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lipidomics profiling and circulating triglyceride concentrations in sub-Saharan African individuals.Scientific reports · 2024Article
- Angiopoietin-like Proteins and Lipoprotein Lipase: The Waltz Partners That Govern Triglyceride-Rich Lipoprotein Metabolism? Impact on Atherogenesis, Dietary Interventions, and Emerging Therapies.Journal of clinical medicine · 2024Article
- Leptin-mediated suppression of lipoprotein lipase cleavage enhances lipid uptake and facilitates lymph node metastasis in gastric cancer.Cancer communications (London, England) · 2024Article
- A unified model for regulating lipoprotein lipase activity.Trends in endocrinology and metabolism: TEM · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The endoplasmic reticulum (ER)-tethered, liver-enriched stress sensor CREBH is processed in response to increased energy demands or hepatic stress to release an amino-terminal fragment that functions as a transcription factor for hepatic genes encoding lipid and glucose metabolic factors. Here, we discovered that the carboxyl-terminal fragment of CREBH (CREBH-C) derived from membrane-bound, full-length CREBH was secreted as a hepatokine in response to fasting or hepatic stress. Phosphorylation of CREBH-C mediated by the kinase CaMKII was required for efficient secretion of CREBH-C through exocytosis. Lipoprotein lipase (LPL) mediates the lipolysis of circulating triglycerides for tissue uptake and is inhibited by a complex consisting of angiopoietin-like (ANGPTL) 3 and ANGPTL8. Secreted CREBH-C blocked the formation of ANGPTL3-ANGPTL8 complexes, leading to increased LPL activity in plasma and metabolic tissues in mice. CREBH-C administration promoted plasma triglyceride clearance and partitioning into peripheral tissues and mitigated hypertriglyceridemia and hepatic steatosis in mice fed a high-fat diet. Individuals with obesity had higher circulating amounts of CREBH-C than control individuals, and human
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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 Socratic graph.