Obesity is a global epidemic that affects 13% of adults world-wide, and over 40% of adults in the United States. Further, obesity contributes substantially to global morbidity and mortality and acts as a major risk factor for type II diabetes, among many other diseases. Therefore, efforts to understand the pathobiology of obesity and generate novel methods of prevention are paramount.

Recent findings suggest the importance of immune cells in the progression and onset of obesity, prominently including microglia, the immune cells of the central nervous system (CNS) , and peripheral macrophages. To this end, our project proposes to explore the role of these immune cells in the etiology and progression of obesity.

Our laboratory found that deletion of the Abi3 gene locus, which is a gene primarily involved in the regulation of actin dynamics within immune cells, resulted in the induction of obesity in mice. Specifically, mice lacking Abi3 had increased body weight and body fat percentage compared to wild-type mice. Additionally, mice without Abi3 showed impaired glucose tolerance and insulin sensitivity, but no changes in acute energy expenditure or food intake. Further, through RNA-seq analysis, we observed that deletion of the Abi3 gene locus substantially altered the expression of immune genes in both the CNS and peripheral tissue.

Through this study, we aimed to metabolically characterize mice with and without the Abi3 gene locus in order to discover the mechanisms by which this deletion alters central and peripheral immune cells to facilitate the onset of obesity. This and future studies will enable us to understand how perturbations to microglia and peripheral immune cells alter metabolic regulation to mediate susceptibility to metabolic disease.


D.C.Smith: None. H.Karahan: None. H.Wijeratne: None. M.Al amin: None. B.Mccord: None. Y.Moon: None. J.Kim: None.


Indiana University Diabetes and Obesity Research Training Program, DK064466

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