A widely accepted explanation for the increasing prevalence of obesity lays on the imbalance between energy intake and energy expenditure. As prevalence continues to rise and economic costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. Recent advances emphasize the impairment of gut epithelial barrier function as a contributing factor, in conjunction with excessive energy intake.
To sustain metabolism, intracellular ATP concentration must be regulated within an appropriate range. This coordination is achieved through the function of the AMP-activated protein kinase (AMPK), a cellular “fuel gauge that represents a point of conversion of regulatory signals monitoring systemic and cellular energy status. Recent evidences indicate that AMPK may also fulfill key functions for the maintenance of IEB integrity but the mechanisms are still poorly understood. Therefore, a more comprehensive analysis of AMPK function in the gastrointestinal tract is needed to uncode the precise effects of AMPK activation on IEB properties.
The overall objective of this project is to study the role of AMPK in the maintenance of IEB homeostasis. The specific aims are 1) to explore the impact of AMPK dysregulation on IEB rupture and development inflammation; 2) to validate strategies of IEB strengthening or restoration by activation of AMPK. Our project will combine molecular and functional analyzes of human pathological/control samples to examination of mice model developing low or high grade chronic inflammation with or without AMPK activation in epithelial cells.