ARRA Investments in Obesity and Inflammation
Public Health Burden
Obesity is characterized by chronic mild inflammation. The main basis for this view is that there is an increased circulating level of several inflammatory markers in the obese. Given the observation that “white” fat secretes a number of inflammation-related proteins, it is probable that this tissue is a major source of the increase in inflammatory markers in obesity. While chronic inflammation is generally considered a consequence of obesity, the new results suggest the inflammatory reaction might also contribute to obesity and associated diseases, including diabetes. It has increasingly been considered that the inflammatory state associated with obesity and the production of inflammatory factors is important in the development of the diseases associated with a high body mass index, a measure of weight relative to height. Thus, diseases associated with obesity, such as type 2 diabetes and cardiovascular disease, have been causally linked to inflammation. However, much work remains to unravel the mechanistic basis for the link between specific inflammatory factors and obesity-related disorders.
Numerous ARRA grants have been funded that are based on studying obesity-associated inflammation and its effects directly in humans:
A project to examine whether omega-3 polyunsaturated fatty acid dietary supplements during pregnancy act as insulin sensitizers thereby decreasing insulin resistance and inflammation.
A study to determine if vascular injury is detectable at a young age in obesity-related high blood pressure, and whether it is associated with a pro-inflammatory adipokine profile which, in turn, is associated with the presence of genetic variants in adipokine regulatory genes in African American children.
A grant to compare the effects of a low-carbohydrate diet with a low-calorie/ low-fat diet, each alone or combined with exercise, on abdominal and liver fat, insulin levels, and inflammation.
A grant to provide insights into the mechanisms by which diet and exercise reduce abdominal fatness and improve cardiovascular health in overweight and obese persons with type 2 diabetes. These mechanisms include systemic inflammation, insulin sensitivity, and aerobic and strength fitness.
A grant to identify demographic and clinical characteristics associated with a higher likelihood of having type 2 diabetes despite being normal weight, and to determine whether three previously-identified risk factors for type 2 diabetes (inflammation, nervous system function, and depression) are predictors of disease in the absence of obesity.
Novel Targets for Intervention
Several ARRA-funded projects are investigating novel methods of obesity interventions focused on inflammation:
A grant to explore the hypothesis that during chronic stress induced by a high fat diet, Grp78 (a multifunctional endoplasmic reticulum (ER) protein) in adipose tissue triggers compensatory and protective measures, such as increases in production of other proteins and mitochondrial activity, which lead to enhanced energy expenditure, attenuation of ER stress and inflammatory responses resulting in improved insulin sensitivity.
A grant to determine how the actions of Tumor Progression Locus 2, a mediator of inflammatory signaling, promote obesity-associated inflammation and insulin resistance.
A grant to test the hypothesis that early life exposure to Bisphenol A promotes adult-onset obesity and related complications (such as diabetes) in mice by altering energy metabolism in key metabolic tissues such as fat and skeletal muscle.
A project to examine the molecular mechanisms controlling fatty acid release from fat tissue, a key step in the induction of insulin resistance during obesity and type 2 diabetes.
A study to investigate whether exposure to ambient fine-particulate pollution combined with a high fat diet will act together to cause increased obesity and type 2 diabetes as measured by outcomes of obesity, inflammation, insulin resistance, and abnormal vascular function in mice.
-- Omega 3 Supplementation Decreases Inflammation and Fetal Obesity in Pregnancy -- Catalano, Patrick Michael (OH)
-- Inflammation and Injury in Obesity Hypertension in African American Adolescents -- Falkner, Bonita (PA)
-- Two Diets With Exercise in Abdominal Obesity: Cardiovascular Effects -- Stewart, Kerry J. (MD)
-- Diet and Exercise in Type 2 Diabetes -- Stewart, Kerry J. (MD)
-- Epidemiologic Studies of Type 2 Diabetes in Normal Weight Adults -- Carnethon, Mercedes Renee (IL)
-- Endoplasmic Reticulum Chaperone as a Regulator of Obesity and Diabetes -- Lee, Amy S. (CA)
-- TPL2: A Central Node in Obesity-Associated Inflammation and Metabolic Disorders -- Greenberg, Andrew (MA)
-- Defining the Role of BPA in Promoting Obesity and Associated Metabolic Complications -- Rubin, Beverly Sharon (MA)
-- The Control of Fatty Acid Release in Adipocytes -- Ruan, Hong (NJ)
-- Obesity Development: Role of Air Pollution and High Fat Diet -- Sun, Qinghua (OH)
Page Last Updated on June 30, 2018
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