Integrin α1-null mice exhibit improved fatty liver when fed a high fat diet despite severe hepatic insulin resistance

Ashley S. Williams (Lead / Corresponding author), Li Kang, Jenny Zheng, Carrie Grueter, Deanna P. Bracy, Freyja D. James, Ambra Pozzi, David H. Wasserman

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    25 Citations (Scopus)


    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 (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 (itga1−/−) and wild-type (itga1+/+) littermates. Using the insulin clamp, we found that insulin-stimulated hepatic glucose production was suppressed by ∼50% in HF-fed itga1+/+ mice. In contrast, it was not suppressed in HF-fed itga1−/− mice, indicating severe hepatic insulin resistance. This was associated with decreased hepatic insulin signaling in HF-fed itga1−/− mice. Interestingly, hepatic triglyceride and diglyceride contents were normalized to chow-fed levels in HF-fed itga1−/− mice. This indicates that hepatic steatosis is dissociated from insulin resistance in HF-fed itga1−/− mice. The decrease in hepatic lipid accumulation in HF-fed itga1−/− 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.
    Original languageEnglish
    Pages (from-to)6546-6557
    Number of pages12
    JournalJournal of Biological Chemistry
    Issue number10
    Early online date15 Jan 2015
    Publication statusPublished - 6 Mar 2015


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