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Morris DL, Rui L. Recent advances in understanding leptin signaling and leptin resistance. Am J Physiol Endocrinol Metab 297: EI247-E1259, 2009. First published September 1, 2009; doi: 10.1152/ajpendo.00274.2009.--The brain controls energy homeostasis and body weight by integrating various metabolic signals. Leptin, an adipose-derived hormone, conveys critical information about peripheral energy storage and availability to the brain. Leptin decreases body weight by both suppressing appetite and promoting energy expenditure. Leptin directly targets hypothalamic neurons, including AgRP and POMC neurons. These leptin-responsive neurons widely connect to other neurons in the brain, forming a sophisticated neurocircuitry that controls energy intake and expenditure. The anorexigenic actions of leptin are mediated by LEPRb, the long form of the leptin receptor, in the hypothalamus. LEPRb activates both JAK2-dependent and -independent pathways, including the STA[T.sub.3], PI 3-kinase, MAPK, AMPK, and mTOR pathways. These pathways act coordinately to form a network that fully mediates leptin response. LEPRb signaling is regulated by both positive (e.g., SH2B1) and negative (e.g., SOCS3 and PTP1B) regulators and by endoplasmic reticulum stress. Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance. doi: 10.1152/ajpendo.00274.2009.

Mesothelioma is a rapidly progressing, asbestos-related tumour. This tumour was once rare and is now showing an increasing incidence worldwide (1) following the vast mining of asbestos, which peaked in [...], Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as 'preterminal.' We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition. Le mesotheliome est une tumeur liee a l'exposition a l'amiante. Lorsqu'il se forme au niveau de la cage thoracique, le mesotheliome se developpe sur la plevre et prend le nom de mesotheliome pleural. Il s'agit de la forme de mesotheliome la plus repandue, puisqu'il represente 70 % de tous les cas. L'autre forme se manifeste dans l'abdomen : on parle alors de mesotheliome peritoneal. C'est la forme que prend une bonne partie des 30 % de cas restants. Il est souvent difficile de diagnostiquer tot le mesotheliome peritoneal parce que ses premieres manifestations passent dans bien des cas a tort pour de banals malaises digestifs. On etablit donc souvent le diagnostic alors que la maladie s'est deja propagee a toute la cavite peritoneale. Les approches therapeutiques ont evolue depuis une dizaine d'annees, passant de chimiotherapies systemiques et chirurgies palliatives a des chirurgies cytoreductrices et des chimiotherapies perioperatoires intraperitoneales. Ces mesures ont permis de faire augmenter nettement la survie chez des patients que l'on jugeait a une epoque en phase << preterminale >>. Nous faisons ici le point sur les connaissances cliniques actuelles relatives au mesotheliome peritoneal dans l'espoir de sensibiliser davantage les medecins a ces approches et de promouvoir ainsi une prise en charge optimale de la maladie.