Global Analyses of Selective Insulin Resistance in Hepatocytes Caused by Palmitate Lipotoxicity.

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 fa

SUBMITTER: Li Z 

PROVIDER: S-EPMC5930403 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature