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Title: Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet
Author: Cairns, Rose
Fischer, Alexander W.
Blanco Muñoz, Patricia
Alvarez Guaita, Anna
Meneses Salas, Elsa
Egert, Antonia
Buechler, Christa
Hoy, Andrew J.
Heeren, Joerg
Enrich Bastús, Carles
Rentero Alfonso, Carles
Grewal, Thomas
Keywords: Insulina
Metabolisme dels lípids
Metabolisme dels glúcids
Cèl·lules hepàtiques
Lipid metabolism
Carbohydrate metabolism
Liver cells
Issue Date: 15-Aug-2018
Publisher: Public Library of Science (PLoS)
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 HFDand 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.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2018, vol. 13, num. 8, p. e0201310
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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