ArticleThe Journal of clinical investigation2016
SORLA facilitates insulin receptor signaling in adipocytes and exacerbates obesity.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- LR11/SorLA and its role in cardiovascular disease.International journal of cardiology. Heart & vasculature · 2026Review
- Maternal obesity imprints methylation marks in oocytes to drive intergenerational metabolic dysfunction.Nature metabolism · 2026Article
- Signaling downstream of tumor-stroma interaction regulates mucinous colorectal adenocarcinoma apicobasal polarity.Nature communications · 2026Article
- Alzheimer's disease risk protein SorLA regulates ER homeostasis and lipid metabolism in human microglia, with conserved effects in neurons.Acta neuropathologica · 2026Article
- Latent tuberculosis infection in high TB disease burden countries dysregulates cellular and immunological profiles which is further enhanced with uncontrolled hyperglycemia.Scientific reports · 2026Article
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- Single-cell analysis of the amphioxus hepatic caecum and vertebrate liver reveals genetic mechanisms of vertebrate liver evolution.Nature ecology & evolution · 2024Article
- SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment.EMBO reports · 2024Article
- SORCS2 activity in pancreatic α-cells safeguards insulin granule formation and release from glucose-stressed β-cells.iScience · 2024Article
- Mice and minipigs with compromised expression of the Alzheimer's disease geneBrain communications · 2024Article
- Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis.Aging cell · 2023Article
- Identification of ecdysone receptor target genes in the worker honey bee brains during foraging behavior.Scientific reports · 2023Article
- The Insulin Receptor: An Important Target for the Development of Novel Medicines and Pesticides.International journal of molecular sciences · 2022Review
- Sortilin drives hypertension by modulating sphingolipid/ceramide homeostasis and by triggering oxidative stress.The Journal of clinical investigation · 2022Article
- Sortilin-related receptor is a druggable therapeutic target in breast cancer.Molecular oncology · 2022Article
- SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat.The Journal of cell biology · 2021Article
- The aminosterol Claramine inhibits β-secretase 1-mediated insulin receptor cleavage.The Journal of biological chemistry · 2021Article
- A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance.Oncogene · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In humans, genetic variation of sortilin-related receptor, L(DLR class) A repeats containing (SORL1), which encodes the intracellular sorting receptor SORLA, is a major genetic risk factor for familial and sporadic forms of Alzheimer's disease. Recent GWAS analysis has also associated SORL1 with obesity in humans and in mouse models, suggesting that this receptor may play a role in regulating metabolism. Here, using mouse models with genetic loss or tissue-specific overexpression of SORLA as well as data from obese human subjects, we observed a gene-dosage effect that links SORLA expression to obesity and glucose tolerance. Overexpression of human SORLA in murine adipose tissue blocked hydrolysis of triacylglycerides and caused excessive adiposity. In contrast, Sorl1 gene inactivation in mice accelerated breakdown of triacylglycerides in adipocytes and protected animals from diet-induced obesity. We then identified the underlying molecular mechanism whereby SORLA promotes insulin-induced suppression of lipolysis in adipocytes. Specifically, we determined that SORLA acts as a sorting factor for the insulin receptor (IR) that redirects internalized receptor molecules from endosomes to the plasma membrane, thereby enhancing IR surface expression and strengthening insulin signal reception in target cells. Our findings provide a molecular mechanism for the association of SORL1 with human obesity and confirm a genetic link between neurodegeneration and metabolism that converges on the receptor SORLA.
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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.