Molecular and neural mediators of leptin action

Abstract

The adipose tissue-derived hormone, leptin, acts via its receptor (LepRb) in the brain to regulate energy balance and neuroendocrine function. Parsing the biology of leptin requires understanding LepRb signaling and the roles for specific signaling pathways in neural and physiological leptin action. Since the leptin acts via a broadly distributed network of LepRb-expressing neurons, understanding the function of each of these LepRb neural populations will also be crucial. Here, we review the status of knowledge regarding the molecular mediators of leptin action and the neural substrate via which leptin acts to regulate physiologic processes. LeptinAdipose tissue produces the hormone leptin in approximate proportion to fat stores. Circulating leptin communicates the level of energy reserves in the periphery to the central nervous system (CNS) in order to suppress food intake and permit energy expenditure (1-4). Adequate leptin levels permit energy expenditure on the processes of reproduction and growth, and similarly regulate other elements of the endocrine and immune systems (4-6). Conversely, lack of leptin signaling due to mutation of leptin (e.g. ob/ob mice) or the leptin receptor (LepR) (e.g. db/db mice) in rodents and humans results in increased food intake in combination with reduced energy expenditure (and thus obesity), plus neuroendocrine dysfunction (including hypothyroidism, decreased growth, infertility and decreased immune function) (1;7-9). Many of the effects of leptin are attributable to effects in the CNS, particularly in the hypothalamus, a site of high LepRb mRNA expression (2;3).

Leptin promotes the proliferation and migration of human breast cancer through the extracellular-signal regulated kinase pathway

“…Leptin acts via multiple intracellular signaling pathways, including STAT3, ERK and PI3K/AKT, to modulate cellular and organismal physiology (41). MAPK and PI3K inhibitors markedly blocked leptin-induced proliferation (42).…”

Obesidad monogénica humana: papel del sistema leptina-melanocortina en la regulación de la ingesta de alimentos y el peso corporal en humanos

“…Dicha hormona atraviesa la barrera hematoencefálica para actuar como una señal indicadora de las reservas energéticas interactuando con su receptor específico a nivel del núcleo arcuato del hipotálamo 7 . Dicho núcleo posee dos tipos de poblaciones neuronales con altos niveles de expresión del receptor de leptina: las neuronas POMC/CART, las cuales transfieren señales anorexigénicas a través de los derivados de la proopiomelanocortina (POMC), y las neuronas AGRP/NPY, que transfieren señales estimuladoras de la ingesta a través del neuropéptido Y (NPY) y la proteína relacionada con Agouti (AGRP) 8 . Ante situaciones de niveles reducidos de leptina (durante el ayuno prolongado o por deficiencia genética de leptina), se favore-ce la expresión de AGRP/NPY, lo que impulsa a una mayor ingesta de alimentos 9 .…”

The levels of the leptin and adiponectin according to body mass index and their relationship with oxidative parameters

“…Endoteliyal hücrelerin leptin ile uyarılması hücre içinde H 2 O 2 ve HO gibi reaktif oksijen türlerinin aşırı birikimine ve metalloproteinaz-1 ekspresyonunda artışa neden olmaktadır (29). Bu artışta leptin aracılı tirozin kinaz reseptörleri de rol oynamaktadır (30). Leptinin bu etkilerini önle-mede N-asetilsistein'in etkin olduğu gösterilmiştir (31).…”