ArticleMolecular & cellular proteomics : MCP2018
Global Analyses of Selective Insulin Resistance in Hepatocytes Caused by Palmitate Lipotoxicity.
Article in Molecular & cellular proteomics : MCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- Cell-intrinsic insulin signaling defects in human iPS cell-derived hepatocytes in type 2 diabetes.The Journal of clinical investigation · 2025Article
- Sesamin alleviates lipid accumulation induced by elaidic acid in L02 cells through TFEB regulated autophagy.Frontiers in nutrition · 2024Article
- Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death.Cell death & disease · 2022Article
- Article
- Sequential lipidomic, metabolomic, and proteomic analyses of serum, liver, and heart tissue specimens from peroxisomal biogenesis factor 11α knockout mice.Analytical and bioanalytical chemistry · 2022Article
- High-fat diet in a mouse insulin-resistant model induces widespread rewiring of the phosphotyrosine signaling network.Molecular systems biology · 2019Article
- Article
- Broken Energy Homeostasis and Obesity Pathogenesis: The Surrounding Concepts.Journal of clinical medicine · 2018Review
- Hexanoic, Octanoic and Decanoic Acids Promote Basal and Insulin-Induced Phosphorylation of the Akt-mTOR Axis and a Balanced Lipid Metabolism in the HepG2 Hepatoma Cell Line.Molecules (Basel, Switzerland) · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity is tightly linked to hepatic steatosis and insulin resistance. One feature of this association is the paradox of selective insulin resistance: insulin fails to suppress hepatic gluconeogenesis but activates lipid synthesis in the liver. How lipid accumulation interferes selectively with some branches of hepatic insulin signaling is not well understood. Here we provide a resource, based on unbiased approaches and established in a simple cell culture system, to enable investigations of the phenomenon of selective insulin resistance. We analyzed the phosphoproteome of insulin-treated human hepatoma cells and identified sites in which palmitate selectively impairs insulin signaling. As an example, we show that palmitate interferes with insulin signaling to FoxO1, a key transcription factor regulating gluconeogenesis, and identify altered FoxO1 cellular compartmentalization as a contributing mechanism for selective insulin resistance. This model system, together with our comprehensive characterization of the proteome, phosphoproteome, and lipidome changes in response to palmitate treatment, provides a novel and useful resource for unraveling the mechanisms underlying selective insulin resistance.
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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.