Obesity Genomics and Metabolomics: a Nexus of Cardiometabolic Risk
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CARDIOVASCULAR GENOMICS (P NATARAJAN, SECTION EDITOR)
Obesity Genomics and Metabolomics: a Nexus of Cardiometabolic Risk Jessica A. Regan 1,2 & Svati H. Shah 1,2 Accepted: 14 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Obesity is a significant international public health epidemic with major downstream consequences on morbidity and mortality. While lifestyle factors contribute, there is an evolving understanding of genomic and metabolomic pathways involved with obesity and its relationship with cardiometabolic risk. This review will provide an overview of some of these important findings from both a biologic and clinical perspective. Recent Findings Recent studies have identified polygenic risk scores and metabolomic biomarkers of obesity and related outcomes, which have also highlighted biological pathways, such as the branched-chain amino acid (BCAA) pathway that is dysregulated in this disease. These biomarkers may help in personalizing obesity interventions and for mitigation of future cardiometabolic risk. Summary A multifaceted approach is necessary to impact the growing epidemic of obesity and related diseases. This will likely include incorporating precision medicine approaches with genomic and metabolomic biomarkers to personalize interventions and improve risk prediction. Keywords Obesity . Genomics . Metabolomics . Cardiometabolic . Polygenic risk score . Branched-chain amino acids
Introduction
Obesity: the Scope of the Problem
The epidemic of overweight and obesity is an important contributor to short- and long-term cardiometabolic morbidity and mortality across the world. The negative health consequences of obesity reach across the life span contributing to adverse outcomes for adults, and unfortunately now even in children. While lifestyle factors such as diet and sedentary behavior contribute, novel insights including from genomic and metabolomic studies have highlighted the underlying biology, and, in parallel, have identified clinically relevant biomarkers for personalized medicine approaches to potentially decrease the prevalence of obesity and improve cardiometabolic outcomes.
Epidemiology The prevalence of overweight (body mass index [BMI] ≥ 25) and obesity (BMI ≥ 30) has reached epidemic proportions in developed countries such as the United States (U.S.), and is starting to increase in prevalence even in the developing world. In the U.S., greater than 40% of adults are obese and Hispanic and Black adults have higher rates of obesity [1]. Internationally, the prevalence of obesity nearly doubled between 1980 and 2014. Sadly, rates of childhood obesity are also rising, creating additional concern for the true extent of long-term health consequences [2]. For example, in the U.S., the 2015–2016 NHANES study reports that 20.6% of children and adolescents 12–19 years old are obese [3]. These rising rates of obesity contribute to significant morbidity and mortality worldwide [4–8]. In 2010, overweight/ obesity were estimated to ac
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