Integrated Clinical and Metabolic Phenotyping of Adults with Hidden Adiposity Open Access
Bellissimo, Moriah P. (Spring 2020)
Abstract
Obesity is a common medical condition characterized by excess body fat that leads to metabolic diseases including cardiovascular disease, type 2 diabetes, and some cancers. In addition to increased total body fat, visceral adipose tissue (VAT), fat stored intra-abdominally, is an independent contributor to metabolic disease risk. Clinical evaluation for obesity often uses body mass index (BMI), a ratio of weight to height. However, evidence indicates that metabolic health is heterogeneous and individuals with the same BMI can have vastly different comorbidities. As a result, use of BMI alone may inaccurately assess metabolic health of individuals. The purpose of this dissertation was to utilize body composition and fat distribution analysis to provide greater insight into metabolic health and obesity pathophysiology.
This dissertation included three cross-sectional studies with the following aims 1) leverage a large cohort of working adults (n=693) to investigate differences in diet quality scores and physical fitness levels between adults categorized as lean, as having normal weight obesity (NWO), or as having overweight-obesity; 2) in a subset of the cohort (n=179), compare the plasma metabolome between the body composition groups using high-resolution metabolomics (HRM); and 3) examine diet quality and body fat distribution between adults with CF (n=24) and age-matched healthy controls (n=25) and determine if these factors are related to clinical assessments.
Adults with NWO had lower physical fitness levels than lean adults and included more females than males. Reported diet quality was similar between NWO and lean adults, but higher diet quality was associated with lower body fat and VAT in all participants. HRM analyses detected metabolic perturbations that were not recognized by classic clinical laboratories. Adults with NWO had metabolomic profiles similar to adults with overweight-obesity, including upregulated linoleic acid metabolism and altered amino acid metabolism. Finally, in the clinical cohort, participants with CF reported lower diet quality scores compared to controls. One-third of adults with CF had NWO and participants with CF had more VAT than age-matched controls, which was related to fasting glucose levels and added sugar intake. Larger studies in longitudinal cohorts are needed to evaluate these relationships and confirm findings.
Table of Contents
CHAPTER 1: Introduction 1
Specific Aims and Hypotheses 2
Chapter 1 References 5
CHAPTER 2: Background 8
Obesity Pathophysiology 8
Visceral Adiposity 9
Principles of Nutrition Assessment Applied to Research in Adiposity 10
Lifestyle Determinants Influencing Adiposity 11
Anthropometric Measures of Adiposity 13
Dual-Energy X-Ray Absorptiometry Assessment of Body Composition 14
Novel Biochemical Markers Linked to Adiposity 16
Aminothiol Redox 16
High-Resolution Metabolomics 17
Normal Weight Obesity 19
Cystic Fibrosis 21
Overall Goal and Significance 23
Overview of Chapters 23
Chapter 2 References 25
CHAPTER 3: Extended Methods 42
Specific Aims and Hypotheses 42
Methods Specific to Chapters 4 and 5 43
Center for Health Discovery (CHD) Study Overview 43
CHD Cohort Study Inclusion and Exclusion Criteria 44
CHD Participant Recruitment 45
Assessments 46
Methods Specific to Chapter 6 56
Integration of Nutritional Metabolomics with Bioenergetics in Cystic Fibrosis Study (BEAM-CF) Overview 56
Participant Selection 57
Assessments 59
Chapter 3 References 65
CHAPTER 4: Physical fitness but not diet quality distinguishes lean and normal weight obese adults 68
Abstract 69
Introduction 72
Materials and Methods 73
Results 77
Discussion 81
Chapter 4 References 86
CHAPTER 5: Plasma high-resolution metabolomics differentiates adults with normal weight obesity from lean individuals 106
Abstract 109
Introduction 110
Methods 111
Results 116
Discussion 119
Chapter 5 References 125
CHAPTER 6: Visceral adipose tissue is associated with poor diet quality and higher fasting glucose in adults with cystic fibrosis 144
Introduction 148
Materials and Methods 149
Results 153
Discussion 155
Chapter 6 References 160
CHAPTER 7: Discussion 177
Key Findings 177
Role of Diet Quality and Physical Fitness on Body Composition 179
Role of Sex on Body Composition 181
Novel Metabolic Pathways Linked to Body Composition 182
Clinical Implications and Future Directions for NWO 183
Clinical Implications and Future Directions for Cystic Fibrosis and Other Catabolic Illnesses 187
Strengths and Limitations 189
Conclusions 190
Chapter 7 References 191
About this Dissertation
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