Cairns, Rose and Fischer, Alexander W. and Blanco-Munoz, Patricia and Alvarez-Guaita, Anna and Meneses-Salas, Elsa and Egert, Antonia and Buechler, Christa and Hoy, Andrew J. and Heeren, Joerg and Enrich, Carlos and Rentero, Carles and Grewal, Thomas (2018) Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet. PLOS ONE, 13 (8): e0201310. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Annexin A6 (AnxA6) controls cholesterol and membrane transport in endo- and exocytosis, and modulates triglyceride accumulation and storage. In addition, AnxA6 acts as a scaffolding protein for negative regulators of growth factor receptors and their effector pathways in many different cell types. Here we investigated the role of AnxA6 in the regulation of whole body lipid metabolism and insulin-regulated glucose homeostasis. Therefore, wildtype (WT) and AnxA6-knockout (KO) mice were fed a high-fat diet (HFD) for 17 weeks. During the course of HFD feeding, AnxA6-KO mice gained less weight compared to controls, which correlated with reduced adiposity. Systemic triglyceride and cholesterol levels of HFD-fed control and AnxA6-KO mice were comparable, with slightly elevated high density lipoprotein (HDL) and reduced triglyceride-rich lipoprotein (TRL) levels in AnxA6-KO mice. AnxA6-KO mice displayed a trend towards improved insulin sensitivity in oral glucose and insulin tolerance tests (OGTT, ITT), which correlated with increased insulin-inducible phosphorylation of protein kinase B (Akt) and ribosomal protein S6 kinase (S6) in liver extracts. However, HFD-fed AnxA6-KO mice failed to downregulate hepatic gluconeogenesis, despite similar insulin levels and insulin signaling activity, as well as expression profiles of insulin-sensitive transcription factors to controls. In addition, increased glycogen storage in livers of HFD-and chow-fed AnxA6-KO animals was observed. Together with an inability to reduce glucose production upon insulin exposure in AnxA6-depleted HuH7 hepatocytes, this implicates AnxA6 contributing to the fine-tuning of hepatic glucose metabolism with potential consequences for the systemic control of glucose in health and disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LOW-DENSITY-LIPOPROTEIN; ANNEXIN A6; CHOLESTEROL TRANSPORT; SIGNALING PATHWAYS; INSULIN-RESISTANCE; APO-B; LIVER; RECEPTOR; METABOLISM; GLUCONEOGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Jan 2020 10:20 |
| Last Modified: | 10 Jan 2020 10:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14048 |
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