|Gonzales, Naomi -|
|Goldie, Lauren -|
Submitted to: Angiogenesis
Publication Type: Abstract Only
Publication Acceptance Date: September 19, 2012
Publication Date: October 14, 2012
Citation: Gonzales, N.M., Goldie, L.C. 2012. Role of leptin signaling in hemato-vascular development and niche function: Leptin receptor-mediated signaling regulates LT-HSC homeostasis in vivo [abstract]. The 2012 North American Vascular Biology Organization (NAVBO) Workshop, Session: Systems Biology of Vascular Disease and Metabolic Syndrome, October 14-18, 2013, Pacific Grove, California. Angiogenesis, 16(1):267-268. Technical Abstract: Homeostatic functioning of the cardiovascular and hematopoietic systems is known to be interdependent and strongly influenced by the microenvironment in which hemato-vascular cells develop and reside. The role of nutrition and metabolism as regulable and dynamic extracellular cues however, remains a significant "black box" in our understanding of how hemato-vascular cells are extrinsically regulated in vivo. Leptin is a circulating adipokine that regulates hypothalamic feedback relays controlling food intake and metabolism. Mice rendered genetically deficient in leptin or unresponsive to leptin signaling thus exist within a metabolic state of perceived starvation; satiety signaling is disrupted, metabolism slows, and obesity prevails, bringing with it a constellation of cardiovascular and immune risk factors collectively termed "metabolic syndrome". These pathological changes are mirrored in both human obesity and experimental high-fat feeding, where they are associated with attenuation of the hypothalamic response to leptin signaling. Leptin receptors are widely expressed throughout the hemato-vascular system, and as a circulating hormone with potent pro-inflammatory and pro-angiogenic activity, leptin has the potential to modulate blood and vascular cell function directly. Data from leptin (ob/ob) and leptin receptor (db/db) deficient mice reveal profound changes in homeostatic regulation of the bone marrow HSC compartment, characterized by progressive loss of LT-HSC and lineage-specific alterations in hematopoietic differentiation potential. We hypothesize that aberrant leptin signaling associated with overnutrition represents a mechanistic link between obesity and associated defects in adaptive immunity.