ArticleThe Journal of clinical investigation2018
Thioesterase-mediated control of cellular calcium homeostasis enables hepatic ER stress.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 36 citations in OpenAlex.
- Acyl-CoA thioesterases and their derived lipid mediators: linking Acyl-CoA metabolic reprogramming to the tumor microenvironment.Frontiers in immunology · 2026Review
- Metabolic dysfunction‑associated steatotic liver disease: Pathogenesis, model and treatment (Review).International journal of molecular medicine · 2025Review
- Dietary phosphorus restriction induced phospholipid deficiency, endoplasmic reticulum stress, inflammatory response and gut microbiota disorders inFrontiers in immunology · 2025Article
- Review
- The functions of CaJournal of cell communication and signaling · 2023Review
- Protective Role of Hepassocin against Hepatic Endoplasmic Reticulum Stress in Mice.International journal of molecular sciences · 2022Article
- GABA and FermentedNutrients · 2022Article
- THEM6-mediated reprogramming of lipid metabolism supports treatment resistance in prostate cancer.EMBO molecular medicine · 2022Article
- Up-regulation of thioesterase superfamily member 2 in skeletal muscle promotes hepatic steatosis and insulin resistance in mice.Hepatology (Baltimore, Md.) · 2022Article
- Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitusFrontiers in nutrition · 2022Article
- Emerging Targets in Type 2 Diabetes and Diabetic Complications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Fascin inhibitor increases intratumoral dendritic cell activation and anti-cancer immunity.Cell reports · 2021Article
- Disruption of Endoplasmic Reticulum Proteostasis in Age-Related Nervous System Disorders.Progress in molecular and subcellular biology · 2021Article
- Targeting CaCancers · 2020Review
- Phosphatidylinositol 3-kinase-δ controls endoplasmic reticulum membrane fluidity and permeability in fungus-induced allergic inflammation in mice.British journal of pharmacology · 2020Article
- Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways.Mediators of inflammation · 2020Review
- Multiple mitochondrial thioesterases have distinct tissue and substrate specificity and CoA regulation, suggesting unique functional roles.The Journal of biological chemistry · 2019Article
- Thioesterase Superfamily Member 2 Promotes Hepatic VLDL Secretion by Channeling Fatty Acids Into Triglyceride Biosynthesis.Hepatology (Baltimore, Md.) · 2019Article
- Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1-induced steatosis.The Journal of biological chemistry · 2019Article
- Metabolites as regulators of insulin sensitivity and metabolism.Nature reviews. Molecular cell biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The incorporation of excess saturated free fatty acids (SFAs) into membrane phospholipids within the ER promotes ER stress, insulin resistance, and hepatic gluconeogenesis. Thioesterase superfamily member 2 (Them2) is a mitochondria-associated long-chain fatty acyl-CoA thioesterase that is activated upon binding phosphatidylcholine transfer protein (PC-TP). Under fasting conditions, the Them2/PC-TP complex directs saturated fatty acyl-CoA toward β-oxidation. Here, we showed that during either chronic overnutrition or acute induction of ER stress, Them2 and PC-TP play critical roles in trafficking SFAs into the glycerolipid biosynthetic pathway to form saturated phospholipids, which ultimately reduce ER membrane fluidity. The Them2/PC-TP complex activated ER stress pathways by enhancing translocon-mediated efflux of ER calcium. The increased cytosolic calcium, in turn, led to the phosphorylation of calcium/calmodulin-dependent protein kinase II, which promoted both hepatic insulin resistance and gluconeogenesis. These findings delineate a mechanistic link between obesity and insulin resistance and establish the Them2/PC-TP complex as an attractive target for the management of hepatic steatosis and insulin resistance.
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.