ArticleThe Journal of biological chemistry2016
Hepatic FOXO1 Target Genes Are Co-regulated by Thyroid Hormone via RICTOR Protein Deacetylation and MTORC2-AKT Protein Inhibition.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 53 citations in OpenAlex.
- Thyroid hormone acts independently of the thyroid hormone receptor beta in hepatocytes to improve systemic insulin sensitivity.Hepatology communications · 2026Article
- Nonlinear Association Between THs, TSH, and HbA1c in Patients With Type 2 Diabetes Mellitus: A Retrospective Study.Journal of diabetes · 2026Article
- Resmetirom and thyroid hormone receptor-targeted treatment for metabolic dysfunction-associated steatotic liver disease (MASLD).Portal hypertension & cirrhosis · 2025Article
- Targeting lipophagy and nuclear receptors in metabolic-associated fatty liver disease: insights from traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Actions of thyroid hormones and thyromimetics on the liver.Nature reviews. Gastroenterology & hepatology · 2025Review
- Impaired thyroid hormone sensitivity is associated with the degrees of fatty infiltration in metabolic dysfunction associated steatotic liver disease.Frontiers in endocrinology · 2025Article
- Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Article
- Metabolic Messengers: Thyroid Hormones.Nature metabolism · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Chronic Exposure to Chlorpyrifos Damages Thyroid Activity and Imbalances Hepatic Thyroid Hormones Signaling and Glucose Metabolism: Dependency of T3-FOXO1 Axis by Hyperglycemia.International journal of molecular sciences · 2023Article
- Hepatic Energy Metabolism under the Local Control of the Thyroid Hormone System.International journal of molecular sciences · 2023Review
- Metabolism-Disrupting Chemicals Affecting the Liver: Screening, Testing, and Molecular Pathway Identification.International journal of molecular sciences · 2023Review
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Important Hormones Regulating Lipid Metabolism.Molecules (Basel, Switzerland) · 2022Review
- Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy.Autophagy · 2022Article
- Higher Free Triiodothyronine Is Associated With Higher HDL Particle Concentration and Smaller HDL Particle Size.The Journal of clinical endocrinology and metabolism · 2022Article
- Endocrine Regulation on Bone by Thyroid.Frontiers in endocrinology · 2022Review
- Effects of Forkhead box O1 on lipopolysaccharide-induced mitochondrial dysfunction in human cervical squamous carcinoma SiHa cells.Oncology letters · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
MTORC2-AKT is a key regulator of carbohydrate metabolism and insulin signaling due to its effects on FOXO1 phosphorylation. Interestingly, both FOXO1 and thyroid hormone (TH) have similar effects on carbohydrate and energy metabolism as well as overlapping transcriptional regulation of many target genes. Currently, little is known about the regulation of MTORC2-AKT or FOXO1 by TH. Accordingly, we performed hepatic transcriptome profiling in mice after FOXO1 knockdown in the absence or presence of TH, and we compared these results with hepatic FOXO1 and THRB1 (TRβ1) ChIP-Seq data. We identified a subset of TH-stimulated FOXO1 target genes that required co-regulation by FOXO1 and TH. TH activation of FOXO1 was directly linked to an increase in SIRT1-MTORC2 interaction and RICTOR deacetylation. This, in turn, led to decreased AKT and FOXO1 phosphorylation. Moreover, TH increased FOXO1 nuclear localization, DNA binding, and target gene transcription by reducing AKT-dependent FOXO1 phosphorylation in a THRB1-dependent manner. These events were associated with TH-mediated oxidative phosphorylation and NAD(+) production and suggested that downstream metabolic effects by TH can post-translationally activate other transcription factors. Our results showed that RICTOR/MTORC2-AKT can integrate convergent hormonal and metabolic signals to provide coordinated and sensitive regulation of hepatic FOXO1-target gene expression.
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.