Skip NavigationSkip to Content
Return Return to Search Results

Liver-specific disruption of PPAR gamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes

  1. Author:
    Matsusue, K.
    Haluzik, M.
    Lambert, G.
    Yim, S. H.
    Gavrilova, O.
    Ward, J. M.
    Brewer, B.
    Reitman, M. L.
    Gonzalez, F. J.

  2. Author Address

    NIH, Bldg 37,Rm 2A19, Bethesda, MD 20892 USA NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, NIH, Frederick, MD USA NCI, Lab Metab, NIH, Frederick, MD USA NIDDKD, Diabet Branch, NIH, Frederick, MD USA NHLBI, Mol Dis Branch, NIH, Frederick, MD USA Gonzalez FJ NIH, Bldg 37,Rm 2A19, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Journal of Clinical Investigation
    1. 111
    2. 5
    3. Pages: 737-747
  4. Type of Article: Article
  1. Abstract:

    To elucidate the function of PPARgamma in leptin-deficient mouse (ob/ob) liver, a PPARgamma liver-null mouse on an ob/ob background, ob/ob-PPARgamma(fl/fl)AlbCre(+), was produced using a floxed PPARgamma allele, PPARgamma(fl/fl), and Cre recombinase under control of the albumin promoter (AlbCre). The liver of ob/ob-PPARgamma(fl/fl)AlbCre(+) mice had a deletion of exon 2 and a corresponding loss of full-length PPARgamma mRNA and protein. The PPARgamma-deficient liver in ob/ob mice was smaller and had a dramatically decreased triglyceride (TG) content compared with equivalent mice lacking the AlbCre transgene (ob/ob-PPARgamma(fl/fl)AlbCre(-)). Messenger RNA levels of the hepatic lipogenic genes, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1, were reduced in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice, and the levels of serum TG and FFA in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice were significantly higher than in the control ob/ob- PPARgamma(fl/fl)AlbCre(-) mice. Rosiglitazone treatment exacerbated the fatty liver in ob/ob-PPARgamma(fl/fl)AlbCre(-) mice compared with livers from nonobese Cre(-) mice; there was no effect of rosiglitazone in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice. The deficiency of hepatic PPARgamma further aggravated the severity of diabetes in ob/ob mice due to decreased insulin sensitivity in muscle and fat. These data indicate that hepatic PPARgamma plays a critical role in the regulation of TG content and in the homeostasis of blood glucose and insulin resistance in steatotic diabetic mice.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel