Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/26999
Title: | Exploring the Relationships Between Liver Fat, Gut Microbiota, Serotonin, and Brown Adipose Tissue in Humans |
Authors: | Ahmed, Basma |
Advisor: | Steinberg, Gregory |
Department: | Biochemistry and Biomedical Sciences |
Keywords: | Brown Adipose Tissue, NAFLD, MRI, Serotonin, Gut microbiota |
Publication Date: | 2021 |
Abstract: | Obesity is a growing problem that impacts both adults and children. Obesity is linked to the development of unfavorable health outcomes like excess fat accumulation in the liver, a problem known as non-alcoholic fatty liver disease (NAFLD). Brown adipose tissue (BAT), a thermogenic body fat that can be turned on by cold, produces heat by consuming circulating lipids and glucose in a futile cycle. Less active cold-stimulated BAT is linked to obesity and type 2 diabetes in adults but whether this relationship exists in children is unknown. In rodents, increases in BAT activity are associated with reductions in NAFLD, effects that may be mediated through changes in the gut microbiome and reductions in peripheral serotonin. Whether the gut microbiome and serotonin play a role in regulating BAT activity in adults and children is not known. In this thesis, we have utilized magnetic resonance imaging (MRI) proton density fat fraction (PDFF) to assess BAT in the supraclavicular (SCV) region after three hours and one hour of whole-body cold exposure in adults and children, respectively. In 60 adults (aged 18-57 years), we examined whether there is a relationship between cold-stimulated BAT activity and liver fat (assessed via MRI) and whether gut microbiota plays a role in connecting these two tissues. In children, we investigated, BAT activity after whole-body cold exposure in 26 boys (aged 8-10 years). We also explored if BAT activity was different between boys with and without overweight/obesity. Finally, in young boys, we measured the levels of serotonin in platelet-poor plasma and its metabolic end product 5-hydroxyindole acetic acid (5-HIAA) in the urine. We explored if these measures of circulating serotonin were related to cold-stimulated BAT activity and if they were different between boys with and without overweight/obesity. The findings from this research indicate that higher cold-stimulated BAT activity is associated with lower liver fat in adults, but that this relationship is unlikely mediated through changes in the gut microbiota. Additionally, boys with overweight/obesity have lower cold-stimulated BAT activity and lower 5-HIAA in their urine compared to those with normal weight. Moreover, circulatory serotonin is negatively related to total adiposity. However, circulating serotonin is not related to cold-stimulated BAT activity in this cohort. These findings are important as they indicate for the first time that increasing BAT activity in adults and children could potentially be a new avenue for the treatment of NAFLD and obesity. |
URI: | http://hdl.handle.net/11375/26999 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Ahmed_Basma_A_September 2021_PhD.pdf | 4.19 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.