GLTP-fold interaction with planar phosphatidylcholine surfaces is synergistically stimulated by phosphatidic acid and phosphatidylethanolamine.

Among amphitropic proteins, human glycolipid transfer protein (GLTP) forms a structurally-unique fold that translocates on/off membranes to specifically transfer glycolipids. Phosphatidylcholine (PC) bilayers with curvature-induced packing stress stimulate much faster glycolipid intervesicular transfer than nonstressed PC bilayers raising questions about planar cytosol-facing biomembranes being viable sites for GLTP interaction. Herein, GLTP-mediated desorption kinetics of fluorescent glycolipid (tetramethyl-boron dipyrromethene (BODIPY)-label) from lipid monolayers are assessed using a novel microfluidics-based surface balance that monitors lipid lateral packing while simultaneously acquiring surface fluorescence data. At biomembrane-like packing (30-35 mN/m), GLTP uptake of BODIPY-glycolipid from POPC monolayers was nearly nonexistent but could be induced by reducing surface pressure to mirror packing in curvature-stressed bilayers. In contrast, 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) matrices supported robust BODIPY-glycolipid uptake by GLTP at both high and low surface pressures. Unexpectedly, negatively-charged cytosol-facing lipids, i.e., phosphatidic acid and phosphatidylserine, also supported BODIPY-glycolipid uptake by GLTP at high surface pressure. Remarkably, including both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate (5 mol%) and POPE (15 mol%) in POPC synergistically activated GLTP at high surface pressure. Our study shows that matrix lipid headgroup composition, rather than molecular packing per se, is a key regulator of GLTP-fold function while demonstrating the novel capabilities of the microfluidics-based film balance for investigating protein-membrane interfacial interactions.

Obesity and breast cancer: status of leptin and adiponectin in pathological processes.

It is well recognized that obesity increases the risk of various cancers, including breast malignancies in postmenopausal women. Furthermore, obesity may adversely affect tumor progression, metastasis, and overall prognosis in both pre- and postmenopausal women with breast cancer. However, the precise mechanism(s) through which obesity acts is/are still elusive and this relationship has been the subject of much investigation and speculation. Recently, adipose tissue and its associated cytokine-like proteins, adipokines, particularly leptin and adiponectin, have been investigated as mediators for the association of obesity with breast cancer. Higher circulating levels of leptin found in obese subjects could be a growth-enhancing factor as supported by in vitro and preclinical studies, whereas low adiponectin levels in obese women may be permissive for leptin's growth-promoting effects. These speculations are supported by in vitro studies which indicate that leptin promotes human breast cancer cell proliferation while adiponectin exhibits anti-proliferative actions. Further, estrogen and its receptors have a definite impact on the response of human breast cancer cell lines to leptin and adiponectin. More in-depth studies are needed to provide additional and precise links between the in vivo development of breast cancer and the balance of adiponectin and leptin.