Introduction Leptin is a cytokine hormone released into circulation from adipose tissue, placenta and stomach, and is best known for its effects on energy balance ( 1 , 2 , 3 , 4 , 5 ). Animals that lack leptin ( ob/ob ), or its long
Robert A Hart, Robin C Dobos, Linda L Agnew, Neil A Smart and James R McFarlane
Juan Carlos Juárez-Cruz, Miriam Daniela Zuñiga-Eulogio, Monserrat Olea-Flores, Eduardo Castañeda-Saucedo, Miguel Ángel Mendoza-Catalán, Carlos Ortuño-Pineda, Ma Elena Moreno-Godínez, Sócrates Villegas-Comonfort, Teresita Padilla-Benavides and Napoleón Navarro-Tito
, which further enhances the predisposition of developing breast tumors ( 4 ). Among these molecules, leptin is one of the most important adipokines involved in the development and progression of mammary tumors ( 5 ). Leptin is a hormone with a molecular
Anna Kistner, Mireille Vanpée and Kerstin Hall
is associated with obesity. Increased body fat percentage in humans has been shown to be correlated with higher leptin levels (12) . Leptin is a peptide hormone produced and secreted from the white adipose tissue (13) . In a population of relatively
Estíbaliz Castillero, Ana Isabel Martín, Maria Paz Nieto-Bona, Carmen Fernández-Galaz, María López-Menduiña, María Ángeles Villanúa and Asunción López-Calderón
lipoprotein metabolism. Adipose tissue is not only an energy storage organ but also an important endocrine organ secreting proteins known as adipokines. Adiponectin and leptin are adipocytokines secreted specifically by adipose cells and both may play an
Henryk F Urbanski, Kevin Mueller and Cynthia L Bethea
. Blood samples were collected from each animal under ketamine HCl sedation (10 mg/kg body weight, intramuscular), at Month −1 and again at Month 24; the serum was stored frozen at −20°C and subsequently assayed for leptin, cortisol and DHEAS. Note
Jana Ernst, Urszula Grabiec, Kathrin Falk, Faramarz Dehghani and Kristina Schaedlich
leptin and decreasing serum adiponectin ( 14 , 15 , 16 ). Accordingly, data from in vitro models showed a DEHP-dependent impairment of adipogenesis and adipocyte function ( 14 , 17 ). Analyses on underlying mechanisms are difficult, because energy
Teresa Vilariño-García, Antonio Pérez-Pérez, Esther Santamaría-López, Nicolás Prados, Manuel Fernández-Sánchez and Victor Sanchez-Margalet
INTRODUCTION: Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, obesity, and insulin resistance, that leads to subfertility. Sam68 is an RNA-binding protein with signaling functions that is ubiquitously expressed, including gonads. Sam68 is recruited to leptin signaling, mediating different leptin actions.
OBJECTIVE: We aimed to investigate the role of Sam68 in leptin signaling mediating the effect on aromatase expression in granulosa cells, and the posible implication of Sam68 in the leptin resistance in PCOS.
MATERIALS AND METHODS: Granulosa cells were from healthy donor (n=25) and women with PCOS (n=25), within age range 20-40 years old, from Valencian Infertility Institute (IVI), Seville, Spain. Sam68 expression was inhibited by siRNA method and overexpressed by expression vector. Expression level was analysed by qPCR and immunoblot. Statistical significance was assessed by ANOVA followed by different post hoc tests. A P value <0.05 was considered statistically significant.
RESULTS: We have found that leptin stimulation increases phosphorylation, and expression level of Sam68, and aromatase in granulosa cells. Downregulation of Sam68 expression resulted in a lower activation of MAPK and PI3K pathways in response to leptin, whereas overexpression of Sam68 increased leptin stimulation of signaling, enhancing aromatase expression. Granulosa cells from women with PCOS presented lower expression of Sam68 and were resistant to the leptin effect on aromatase expression.
CONCLUSIONS: These results suggest the participation of Sam68 in leptin receptor signaling, mediating the leptin effect on aromatase expression in granulosa cells, and points to a new target in leptin resistance in PCOS.
Hichem Bouguerra, Amal Gorrab, Stephan Clavel, Hammouda Boussen, Jean François Louet and Asma Gati
Large prospective studies established a link between obesity and breast cancer (BC) development. Yet, the mechanisms underlying this association are not fully understood. Among the diverse adipocytokine secreted by hypertrophic adipose tissue, leptin is emerging as a key candidate molecule linking obesity and cancer, since it promotes proliferation and invasiveness of tumors. However, the potential implication of leptin on tumor escape mechanisms remains unknown. This study aims to explore the effect of leptin on tumor resistance to NK lysis and the underlying mechanism. We found that leptin promotes both BC resistance to NK92-mediated lysis and β oxidation on MCF-7, by the up-regulation of a master regulator of mitochondrial biogenesis, peroxisome proliferator activated receptor coactivator-1 α (PGC-1α). Using adenoviral approaches, we show that acute elevation of PGC-1α enhances the fatty acid oxidation pathway and decreases the susceptibility of BC cells to NK92-mediated lysis. Importantly, we identified new regulatory functions of PGC-1α and leptin in regulating the expression of hypoxia-inducible factor-1 alpha (HIF-1α by tumor cells, a transcriptional factor with pleiotropic role in cancer. We further demonstrate that basal BC cells MDA-MB-231 and BT-20 exhibit an increased PGC-1α mRNA level, an enhanced activity of oxidative phosphorylation and are more resistance to NK92 lysis in comparison with luminal BC cells (MCF7 and MDA-361). Altogether, our results demonstrate for the first time how leptin could promote tumor resistance to immune attacks. Reagents blocking leptin or PGC-1α activity might aid in developing new therapeutic strategies to limit tumor development in obese BC patients.
Katarzyna Wyskida, Grzegorz Franik, Tomasz Wikarek, Aleksander Owczarek, Alham Delroba, Jerzy Chudek, Jerzy Sikora and Magdalena Olszanecka-Glinianowicz
Introduction It has been shown that the levels of different adipokines, such as leptin, adiponectin, resistin, vaspin, omentin-1 and RBP4 are higher in women than those in men ( 1 , 2 , 3 , 4 , 5 , 6 ), and that estrogens stimulate
Benjamin Paul Green, Javier Thomas Gonzalez, Kevin Thomas, Emma Stevenson and Penny Louise Sheena Rumbold
) , glucagon (3) , insulin (4) , and leptin (5) , among others, represent several commonly measured metabolic variables documented as key effectors targeting energy intake and expenditure. Accurate quantification of these peptides is therefore essential when