| The carcinoembryonic antigen related cell adhesion molecule (CEACAM) family of proteins has been implicated to play roles in insulin signaling, lipogenesis, immunity, and tumor suppression. We report the generation of a murine model in which Ceacam2 expression has been deleted. The male Ceacam2 knockout mice exhibit increased insulin secretion and overall remain insulin sensitive. Female Ceacam2 knockout mice, however, are insulin and leptin resistant, with hyperphagia and decreased energy expenditure. Incomplete oxidation in the muscle of the female Ceacam2 knockout mice results in an uncoupling from the citric acid cycle that results in an impairment in substrate switching between fatty acids and glucose. We also show the hepatic insulin resistance produced when Ceacam1 is deleted from the mouse, and how consumption of a high fat diet can cause the L-SACC1 murine model to progress from insulin resistance and fatty liver disease to steatohepatitis. These studies further our understanding of the role of CEACAM proteins in the regulation of energy balance and insulin action. |
