| First Author | Williams AS | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 10 | Pages | 6546-57 |
| PubMed ID | 25593319 | Mgi Jnum | J:219330 |
| Mgi Id | MGI:5620528 | Doi | 10.1074/jbc.M114.615716 |
| Citation | Williams AS, et al. (2015) Integrin alpha1-null Mice Exhibit Improved Fatty Liver When Fed a High Fat Diet Despite Severe Hepatic Insulin Resistance. J Biol Chem 290(10):6546-57 |
| abstractText | Hepatic insulin resistance is associated with increased collagen. Integrin alpha1beta1 is a collagen-binding receptor expressed on hepatocytes. Here, we show that expression of the alpha1 subunit is increased in hepatocytes isolated from high fat (HF)-fed mice. To determine whether the integrin alpha1 subunit protects against impairments in hepatic glucose metabolism, we analyzed glucose tolerance and insulin sensitivity in HF-fed integrin alpha1-null (itga1(-/-)) and wild-type (itga1(+/+)) littermates. Using the insulin clamp, we found that insulin-stimulated hepatic glucose production was suppressed by approximately 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. |
