Tilves, Curtis
(2017)
Association of lipopolysaccharide-binding protein with increases in liver fat in African ancestry men.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a disease with increasing prevalence worldwide, especially in developed countries. While the etiology of NAFLD is complex, the intestinal microbiome may play a role in the development of liver steatosis through bacterial-induced inflammation. Lipopolysaccharide-binding protein (LBP) is an acute-phase protein produced by the liver and which facilitates bacterial-induced inflammation. LBP levels in the serum tend to be low but are raised during infection or in the presence of bacterial components; thus, levels of LBP are considered to be reflective of bacterial-induced inflammation. While the association of LBP with NAFLD has been investigated in cross-sectional studies, no longitudinal studies have been done to determine if LBP levels are associated with liver fat accumulation. Furthermore, no studies have been performed which show the heritability of LBP levels, which may affect susceptibility to the inflammatory response. Elucidation of the role of LBP in NAFLD can provide insights into the etiology of NAFLD and provide a mechanistic link between the intestinal microbiome and liver fat accumulation, yielding public health importance for the understanding and treatment of NAFLD. This study is the first longitudinal study to look at the associations of LBP with the development of steatosis and it is the first study to determine the heritability of LBP in any population, thus supplying novel information on the associations between LBP and liver fat accumulation.
A large family-based study of African ancestry men and women (N = 470) and a large prospective cohort study of African ancestry men (N = 2853) from Tobago were used for this study. LBP was measured in all individuals in the family study. Heritability analyses were performed using SOLAR. In the prospective cohort study, LBP levels were measured at baseline visit (2004-2007), and liver fat was assessed at the follow-up visit (2013-2016, ~10 years later) by computerized tomography (CT) scan, with an overlap of 204 men having both LBP and liver CT completed. Associations were assessed using Spearman correlations and regression analyses. LBP levels in the families were found to have no residual heritability, suggesting that LBP might be entirely environmentally determined in this population. In the prospective cohort, LBP was associated with liver fat infiltration in multivariable analyses which included BMI (p = 0.0469), but not in models which instead included waist circumference. In conclusion, we determined that among African ancestry individuals, LBP levels are completely environmentally determined and that levels may be associated with increases in liver fat accumulation.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 June 2017 |
| Date Type: |
Publication |
| Defense Date: |
4 April 2017 |
| Approval Date: |
29 June 2017 |
| Submission Date: |
13 March 2017 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
47 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
NAFLD, Steatosis, Liver, Microbiome, LBP, African Ancestry |
| Date Deposited: |
29 Jun 2017 23:34 |
| Last Modified: |
01 May 2019 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/30954 |
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