Williams 2015 J Biol Chem

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Williams AS, Kang L, Zheng J, Grueter CA, Bracy DP, James FD, Pozzi A, Wasserman DH (2015) Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance. J Biol Chem 290:6546-57.

» PMID:25593319

Williams AS, Kang L, Zheng J, Grueter CA, Bracy DP, James FD, Pozzi A, Wasserman DH (2015) J Biol Chem

Abstract: Hepatic insulin resistance is associated with increased collagen. Integrin α1β1 is a collagen binding receptor expressed on hepatocytes. Here we show that expression of the α1 subunit is increased in hepatocytes isolated from high fat fed (HF-fed) mice. To determine whether the integrin α1 subunit protects against impairments in hepatic glucose metabolism, we analyzed glucose tolerance and insulin sensitivity in HF-fed integrin α1-null (itgα1-/-) and wild-type littermates (itgα1+/+). Using the insulin clamp, we found that insulin-stimulated hepatic glucose production was suppressed by ~50% in HF-fed itgα1+/+ mice. In contrast, it was not suppressed in HF-fed itgα1-/- mice indicating severe hepatic insulin resistance. This was associated with decreased hepatic insulin signaling in HF-fed itgα1-/- mice. Interestingly, hepatic triglyceride and diglyceride content were normalized to chow-fed levels in HF-fed itgα1-/- mice. This indicates that hepatic steatosis is dissociated from insulin resistance in HF-fed itgα1-/- mice. The decrease in hepatic lipid accumulation in HF-fed itgα1-/- mice was associated with altered free fatty acid metabolism. These studies establish a role for integrin signaling in facilitating hepatic insulin action, while promoting lipid accumulation in mice challenged with a HF diet.

Copyright © 2015, The American Society for Biochemistry and Molecular Biology.

Keywords: Extracellular matrix, Insulin resistance, Integrin lipid metabolism Liver metabolism

O2k-Network Lab: US TN Nashville Wasserman DH

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Liver, Other cell lines  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS  Pathway: F, N  HRR: Oxygraph-2k