Structure and function of the intestinal epithelial barrier (IEB) are dependent upon the integrity of junctional protein structures sealing the apical surface between epithelial cells. Tight junctions (TJ) and the surrounding apical F-actin cytoskeleton are involved in the regulation of paracellular permeability. The regulation of actin cytoskeleton organization by RhoA/Rho-kinase (ROCK) pathway plays an important role in TJ assembly and function. There is mounting evidence that the adipocyte-derived hormone leptin exerts pleiotropic effects on the intestinal epithelium including nutrient absorption, epithelial growth, inflammation and injury. Leptin activates multiple cell signaling pathways in intestinal epithelial cells (IEC) that can explain these pleiotropic effects. However, these pathways are also involved in the primary role of leptin that is the regulation of energy and glucose metabolism homeostasis. In this commentary, we examine how the interplay between leptin signaling pathways that regulate cell metabolism could impact upon IEB function.
Keywords: AMPK; AMPK, AMP-activated protein kinase; IEB, intestinal epithelial barrier; IEC, intestinal epithelial cells; JAK, Janus kinase; JAK/STAT; LepR-b, leptin receptor; MEF, mouse embryonic fibroblast; MLC, myosin light chain; ROCK, Rho-kinase; RhoA/ROCK; STAT, signal transducer and activator of transcription; TJ, tight junctions; VAT, visceral adipose tissue; barrier repair; intestinal epithelial barrier; leptin; metabolism; tight-junction.