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ARRA Investments in Genetics of Obesity

Public Health Burden
Obesity is a major public health problem that is principally a result of excessive energy intake and reduced physical activity.  While environmental factors such as poor diet and lack of exercise are important determinants of obesity, they can be strongly modulated by genetic factors that help determine whether or not an individual will become obese.

Prenatal Environment, Epigenetics, and Epigenomics
Extensive epidemiologic evidence has linked many early life and environmental factors to adult-onset diseases. One plausible mechanism for how the environment could alter disease risk later in life is through genetic effects on cells, leading to activation or silencing of key genes in critical pathways. Thus, people with identical genes, such as twins, may have different disease outcomes because of differential changes in DNA that affect the ability of specific genes to produce specific proteins.  Examples of ARRA-funded projects exploring this topic are:
  • A grant to examine the associations between maternal famine exposure in the different stages of pregnancy and gene expression patterns in adulthood; and how variations in gene expression in adulthood are related to disease risk factors for cardio-vascular disease and diabetes such as obesity.1
  • A grant studying the relationships among maternal diets in early pregnancy, global gene expression patterns during early and late pregnancy, and adiposity-related outcomes in 3- and 7-year-old offspring.2
Complications of Obesity
Obesity is a strong risk factor for several complications such as type 2 diabetes, fatty liver disease, cardiovascular diseases, and many other disorders.  However, not all obese individuals develop these diseases, and variations in an individual’s genetic profile may have significant influence on disease development and progression.  Examples of ARRA-funded projects exploring this topic are:
  • A study that will determine if blood vessel injury can be detected in African-American adolescents who have obesity-related high blood pressure and identify the molecular signature and genetic variations that may be associated with injury.3
  • A project that will determine if physical activity reduces the amount of a protein on the surface of immune cells that is involved in communicating with fat cells to cause high blood pressure and atherosclerosis.4
Systems Biology (Integrated Molecular Control of Physiological Processes)
ARRA grants are focused on defining the molecular circuits controlling physiological processes that influence energy expenditure and body weight, which can serve as key targets for preventing or treating obesity:
  • A study that will use the fruit fly as a simple genetic model system to define the fundamental mechanisms that control lipid metabolism with the goal of providing new directions for understanding and treating human metabolic disorders.5
  • A grant to use genomic and systems biology techniques to identify "switch" genes that enable stable weight loss in the honey bee, and to test that these genes regulate body weight and energy metabolism in mammals.  The bee is useful for this purpose because it undergoes a striking, predictable, and stable loss of abdominal fat as it matures.6
  • A project that will study how molecular pathways and factors in the brain respond to changes in nutrient availability to turn on or off specific genes that control body weight.7

  1. 1RC1HD063549-01 -- Exploring Persistent Epigenetic Changes After Prenatal Famine Exposure in Humans -- Lumey, L.H. (NY)
  2. 1RC1HD063590-01 -- Epidemiology & Epigenetics: Maternal Diet, DNA Methylation, & Offspring Adiposity -- Gillman, Matthew W. (MA)
  3. 1R01HL092030-01A1 -- Inflammation and Injury in Obesity Hypertension in African American Adolescents -- Falkner, Bonita (PA)
  4. 1R21HL093663-01A1 -- Influence of Physical Activity on Leptin Receptor Expression in Adult Women -- Cannon, Joseph G. (GA)
  5. 1RC1DK086426-01 -- A Drosophila Model for Genetic Studies of Metabolism -- Thummel, Carl S. (UT)
  6. 1R01DK082605-01A1 -- Regulation of Stable Fat Loss in a Model System -- Robinson, Gene E. (IL)
  7. 1RC1DK086655-01 -- Small RNAs: Regulation and Regulatory Activity in Body Weight Control -- Good, Deborah Jean (VA)

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