Impact of Obesity and Leptin on Protein Expression Profiles in Mouse Colon

Elevated leptin levels in obesity are associated with increased risk of colon pathology, implicating leptin signaling in colon disease. However, leptin-regulated processes in the colon are currently uncharacterized. Previously, we demonstrated that leptin receptors are expressed on colon epithelium and that increased adiposity and elevated plasma leptin in rats are associated with perturbed metabolism in colon tissue. Thus, we hypothesize that obesity disrupts expression of proteins regulated by leptin in the colon. A proteomic analysis was conducted to investigate firstly, differences in the colon of mice lacking leptin and leptin signaling (ob/ob and db/db, respectively) by comparing protein expression profiles with wild-type mice. Secondly, responses to leptin challenge in wild-type mice and ob/ob mice were compared to identify leptin-regulated proteins and associated cellular processes. Forty proteins were identified with significantly altered expression patterns associated with differences in leptin status in comparisons between all groups of mice. These proteins are associated with calcium binding, cell cycle, cell proliferation, electron transport chain, energy metabolism, protein folding and transport, redox regulation, structural proteins, and proteins involved in transport and regulation of mucus production. This study provides evidence that obesity and leptin significantly alter protein profiles of a number of proteins linked to cellular processes in colon tissues that may be linked to the increased risk of colon pathology associated with obesity.