Abstract

Infiltration of immune cells into visceral adipose tissue is observed in type 2 diabetes development. Monocytes are recruited to obese visceral adipose tissue in large numbers and retain the ability to differentiate into dendritic cells, important antigen presenting cells in the immune system. Differentiation of monocytes into dendritic cells likely accounts for the increased number of dendritic cells observed in the adipose tissue of type 2 diabetic patients. We have demonstrated this differentiation process is regulated in part by a major reduction of linker histone proteins. In adipose tissue, dendritic cells are exposed to high levels of saturated fatty acids. Increased saturated fatty acid levels derived from high fat diets are strongly associated with chronic adipose tissue inflammation. Palmitic acid, the most abundant of saturated fatty acids, is pro-inflammatory and has been linked to insulin resistance. However, the mechanisms underlying palmitic acid induction of inflammation remain unknown. We have confirmed palmitic acid binding to Toll-like receptor 4 (TLR4) on human dendritic cells. In response to palmitic acid activation of TLR4, dendritic cells were shown to secrete pro-inflammatory cytokines that may lead to insulin resistance. In addition, we identified anti-palmitic acid IgG antibodies in the serum of patients with unmanaged type 2 diabetes. In conclusion, diet-derived saturated fatty acids may act as mediators of chronic inflammation associated with type 2 diabetes. Together, the experimental data presented support the hypothesis that palmitic acid is an inducer of dendritic cell induced inflammation and is an important target for type 2 diabetes therapy.

LLU Discipline

Biochemistry

Department

Basic Sciences

School

School of Medicine

First Advisor

Langridge, William H. R.

Second Advisor

De Leon, Marino

Third Advisor

Firek, Anthony

Fourth Advisor

Payne, Kimberly J.

Fifth Advisor

Perry, Christopher C.

Sixth Advisor

Soto-Wegner, Ubaldo

Seventh Advisor

Wall, Nathan

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2015

Date (Title Page)

9-2015

Language

English

Library of Congress/MESH Subject Headings

Adipose Tissue - Cytology; Antigen-Presenting Cells; Dendric Cells; Diabetes Mellitus - Type 2; Diet - High Fat; Dietary Fats; Fatty Acids; Inflammasomes; Insulin Resistance; Macrophage Inflammatory Proteins; Palmitic Acid; Toll-Like Receptors

Subject - Local

Immune cells; Monocytes; Linker Histone Proteins; Chronic Adipose Tissue Inflammation;

Type

Dissertation

Page Count

167

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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