| First Author | Key CC | Year | 2017 |
| Journal | Cell Rep | Volume | 19 |
| Issue | 10 | Pages | 2116-2129 |
| PubMed ID | 28591582 | Mgi Jnum | J:255881 |
| Mgi Id | MGI:6103205 | Doi | 10.1016/j.celrep.2017.05.032 |
| Citation | Key CC, et al. (2017) Hepatocyte ABCA1 Deletion Impairs Liver Insulin Signaling and Lipogenesis. Cell Rep 19(10):2116-2129 |
| abstractText | Plasma membrane (PM) free cholesterol (FC) is emerging as an important modulator of signal transduction. Here, we show that hepatocyte-specific knockout (HSKO) of the cellular FC exporter, ATP-binding cassette transporter A1 (ABCA1), leads to decreased PM FC content and defective trafficking of lysosomal FC to the PM. Compared with controls, chow-fed HSKO mice had reduced hepatic (1) insulin-stimulated Akt phosphorylation, (2) activation of the lipogenic transcription factor Sterol Regulatory Element Binding Protein (SREBP)-1c, and (3) lipogenic gene expression. Consequently, Western-type diet-fed HSKO mice were protected from steatosis. Surprisingly, HSKO mice had intact glucose metabolism; they showed normal gluconeogenic gene suppression in response to re-feeding and normal glucose and insulin tolerance. We conclude that: (1) ABCA1 maintains optimal hepatocyte PM FC, through intracellular FC trafficking, for efficient insulin signaling; and (2) hepatocyte ABCA1 deletion produces a form of selective insulin resistance so that lipogenesis is suppressed but glucose metabolism remains normal. |
