Integrating the Genetic and Metabolic Faces of Obesity

Summary

The goal of this study is to determine why some obese individuals develop insulin resistance and others do not. We hypothesize that an impairment in differentiation of fat cells (adipocytes) is responsible for the development of insulin resistance in select obese individuals. This study will evaluate obese individuals at baseline with respect to characteristics of adipocytes, including gene expression, and will then entail randomizing subjects to either weight loss or treatment with an insulin sensitizing drug (pioglitazone). Changes in insulin resistance will be associated with changes in adipocyte morphology and gene expression.

Timeline

Start

2005-10

Primary completion

2012-10

Completion

2012-10

Publications

• McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, Hui Yen Chng M, Engleman E. T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2637-43. doi: 10.1161/ATVBAHA.114.304636. Epub 2014 Oct 23.
• McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011 Nov;96(11):E1756-60. doi: 10.1210/jc.2011-0615. Epub 2011 Aug 24.
• McLaughlin T, Deng A, Yee G, Lamendola C, Reaven G, Tsao PS, Cushman SW, Sherman A. Inflammation in subcutaneous adipose tissue: relationship to adipose cell size. Diabetologia. 2010 Feb;53(2):369-77. doi: 10.1007/s00125-009-1496-3. Epub 2009 Oct 9.
• McLaughlin T, Deng A, Gonzales O, Aillaud M, Yee G, Lamendola C, Abbasi F, Connolly AJ, Sherman A, Cushman SW, Reaven G, Tsao PS. Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women. Diabetologia. 2008 Dec;51(12):2303-8. doi: 10.1007/s00125-008-1148-z. Epub 2008 Sep 30.

Drugs

Indications