The effects of obesity and the role of the transcription factor NF-kappa B in liver regeneration.

Format:

Book

Thesis/Dissertation

Author/Creator:

DeAngelis, Robert Anthony.

Contributor:

Taub, Rebecca, advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Physiology.

Molecular biology.

0307.

0433.

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

Local Subjects:

Penn dissertations--Cell and molecular biology.

Cell and molecular biology--Penn dissertations.

0307.

0433.

Physical Description:

220 pages

Contained In:

Dissertation Abstracts International 64-05B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Several factors are rapidly activated during liver regeneration following partial hepatectomy or carbon tetrachloride (CCl4)-mediated liver injury, including the transcription factor NF-kappaB. NF-kappaB is felt to be important in proliferative and antiapoptotic regenerative responses, but in vivo genetic studies have been difficult due to lethality or developmental problems with mice deficient for NF-kappaB subunits. However, mice lacking the NF-kappaB p50 subunit (p50-/-) are viable and show few abnormalities, providing a model for the study of liver regeneration in the absence of NF-kappaB. Following partial hepatectomy, p50-/- livers could fully regenerate, despite absent NF-kappaB and decreased STAT3 transcription factor DNA binding. Compensation may have occurred through increased nuclear levels of the NF-kappaB p65 subunit and decreased levels of the NF-kappaB inhibitor IkappaBalpha. Following CCl4 treatment, liver regeneration was not severely impaired in p50-/- mice, but histological analysis indicated slightly less overall liver damage. After injection of Fas antibody, p50-/- livers showed an earlier onset of nuclear changes consistent with apoptosis. Feeding mice a high-fat diet results in obesity and steatosis (fatty liver), which can cause problems with liver regeneration, possibly related to impaired NF-kappaB function. In obese mice, liver regeneration occurred at a slower rate, and livers showed more damage and slight impairment of function. NF-kappaB activity was slightly decreased, while IkappaBalpha levels were increased. After CCl4 injection, obese mice showed much greater liver damage and increased morbidity and mortality. Thus, these results indicate that the p50 subunit of NF-kappaB is not critical for liver regeneration, and that p65 can compensate. Increased p65 may confer greater protection to the liver during toxin-induced damage. Obesity interferes with proliferative responses to slow down regeneration, possibly due to decreased NF-kappaB induction, and sensitizes the liver to damage after partial hepatectomy, and especially after toxic damage, which may be more fatal. These studies further define the role of NF-kappaB in the regenerative responses of the liver.

Notes:

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2003.

Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 2033.

Adviser: Rebecca Taub.

Local Notes:

School code: 0175.

ISBN:

9780496375882

Access Restriction:

Restricted for use by site license.