Adipose-Macrophage Crosstalk by TREM-2 during Obesity

Obesity, characterized by excess white adipose tissue expansion, is a significant medical issue worldwide. Indeed, the rise in worldwide obesity rates has resulted in an explosion of obesity related health problems including type 2 diabetes, cardiovascular disease and fatty liver disease. During obesity, adipose expansion is pathologically accelerated and immune cells called macrophages accumulate, where they contribute to the ensuing metabolically triggered inflammation (metaflammation) and insulin resistance that is characteristic of patients suffering from type 2 diabetes. However, the regulation of this cold nutrient driven inflammation and the interplay between adipocytes and macrophages and the consequences herein on obesity and insulin sensitivity is poorly understood. A deeper understanding of this process could provide attractive avenues for potential therapeutic intervention and reduce human suffering. Our preliminary data demonstrate that the triggering receptor expressed on myeloid cells 2 (TREM-2) is a central regulator of adipose tissue driven insulin resistance. However, we still require a more detailed understanding of how TREM-2 exerts these effects. We will address the molecular mechanisms further using cutting edge approaches that encompass mouse models and systems biology. We expect these studies to provide significant insights into how metaflammation is fine-tuned and the modulatory properties of TREM-2 could have substantial translational impact for type 2 diabetes patients.

Obesity, characterized by excess white adipose tissue expansion, is a significant medical issue worldwide. Indeed, the rise in worldwide obesity rates has resulted in an explosion of obesity related health problems including type 2 diabetes, cardiovascular disease and fatty liver disease. During obesity, adipose expansion is pathologically accelerated and immune cells called macrophages accumulate, where they contribute to the ensuing metabolically triggered inflammation (metaflammation) and insulin resistance that is characteristic of patients suffering from type 2 diabetes. However, the regulation of this "cold" nutrient driven inflammation and the interplay between adipocytes and macrophages and the consequences herein on obesity and insulin sensitivity is poorly understood. A deeper understanding of this process could provide attractive avenues for potential therapeutic intervention and reduce human suffering. Our preliminary data demonstrate that the triggering receptor expressed on myeloid cells 2 (TREM-2) is a central regulator of adipose tissue driven insulin resistance. However, we still require a more detailed understanding of how TREM-2 exerts these effects. We will address the molecular mechanisms further using cutting edge approaches that encompass mouse models and systems biology. We expect these studies to provide significant insights into how metaflammation is fine-tuned and the modulatory properties of TREM-2 could have substantial translational impact for type 2 diabetes patients.