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Martina Holubová, Jana Zemenová, Barbora Mikulášková, Vladimíra Panajotova, Jiří Stöhr, Martin Haluzík, Jaroslav Kuneš, Blanka Železná and Lenka Maletínská

standard diet. In addition to the DIO rat model, the Zucker diabetic rat model, which is a model with impaired leptin receptor signaling ( Fellmann et al . 2013 ), is frequently used for studying the potential of anti-obesity and anti-diabetic peptidic

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Sharon E Mitchell, Ruben Nogueiras, Kellie Rance, D Vernon Rayner, Sharon Wood, Carlos Dieguez and Lynda M Williams

( Williams et al. 2001 ). These cells respond to peripheral hormones that signal both the long- and short-term energy status of the animal. Leptin, secreted by, and in proportion to, WATenters the brain via the short forms of the leptin receptor (Ob-Ra and

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Margaret B Allison and Martin G Myers Jr

( Montague et al . 1997 , Farooqi et al . 1999 ). Leptin receptor (LepRb)-deficient humans and db/db mice display a similar phenotype ( Tartaglia et al . 1995 , Chua et al . 1996 ). Numerous studies have elaborated the critical role of leptin in the

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Jeremy T Smith, Peter J Mark and Brendan J Waddell

providing a key signal for the timing of puberty ( Cheung et al. 1997 , Nagatani et al. 1998 ). Accordingly, puberty onset in ob/ob mice occurs only after administration of exogenous leptin ( Zhang et al. 1994 ). The leptin receptor is a member of

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I Sadaf Farooqi and Stephen O'Rahilly

Discovery of mutations in leptin and the leptin receptor in humans Early studies carried out in obese humans showed that leptin mRNA concentrations in adipose tissue and serum leptin concentrations correlated positively and very closely with the

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Massimo Zerani, Cristiano Boiti, Danilo Zampini, Gabriele Brecchia, Cecilia Dall’Aglio, Piero Ceccarelli and Anna Gobbetti

Leydig cells ( Caprio et al. 1999 ). The leptin receptor shows six isoforms (Ob-Ra-f) arising from mRNA splice variants ( Houseknecht et al. 1998 , Sweeney 2002 ). The extracellular and transmembrane domains are identical in Ob-Ra-d and Ob

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Hiroyuki Shimizu, Kinji Inoue and Masatomo Mori

of the leptin receptor (Ob-Rb) that is localized in the Arc ( Friedman & Halaas 1998 , Schwartz et al. 2000 ), where the POMC-expressing neurons co-localize with Ob-Rb ( Cheung et al. 1997 , Munzberg et al. 2003 ). Certain physiological

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F Dong, X Zhang, X Yang, L B Esberg, H Yang, Z Zhang, B Culver and J Ren

gene) and hyperleptinemia (such as db/db mice with a leptin receptor mutation) trigger overt obesity ( Ross et al. 2004 ). Studies from our laboratory revealed that leptin directly depresses cardiac contraction in ventricular myocytes ( Nickola et

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Camila Calvino, Luana L Souza, Ricardo H Costa-e-Sousa, Norma A S Almeida, Isis H Trevenzoli and Carmen C Pazos-Moura

neurons respectively ( Legradi et al . 1997 , Kim et al . 2000 , Nillni et al . 2000 , Harris et al . 2001 ). The action of leptin is initiated by its binding to the long form of the leptin receptor (ObRb) at the plasma membrane, triggering a

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Farid F Chehab

reproduction and were analogous to Coleman's groundbreaking parabiosis experiments that provided a framework for the roles of leptin and leptin receptor. It was not until leptin rescued the sterility of ob/ob mice ( Chehab et al . 1996 , Mounzih et al