Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications

Abstract

SUMMARYLeptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607 Keywords Leptin; immunity; inflammation; cytokines SUMÁRIO A leptina, uma adipocina produzida principalmente pelo tecido adiposo branco, tem um papel importante não somente na regulação da ingestão alimentar, mas também no controle da imunidade e da inflamação. Já foi amplamente demonstrado que a ausência de leptina causa deficiências imunológicas em modelos animais e em humanos, levando ao aumento da mortalidade. A leptina também regula a inflamação por meio da ação em seu receptor, amplamente distribuído em diversos tipos de células do sistema imunológico. Os mecanismos moleculares pelos quais a leptina determina suas ações biológicas foram recentemente elucidados, e três cascatas intracelulares são ativadas pela leptina: JAK-STAT, PI3K e ERK 1/2. Essas cascatas são reguladas por proteínas intracelulares, reduzindo as ações da leptina. Nesta revisão, são discutidos os mecanismos moleculares pelos quais a leptina regula a imunidade e a inflamação, associando-os a enfermidades inflamatórias crônicas. Arq Bras Endocrinol Metab. 2012;56(9):597-607 Descritores

Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

“…33 Leptin is a hormone/cytokine synthetized by the white adipose tissue, with various functions such as regulation of appetite and energy expenditure via the hypothalamic effects on satiety, in addition to regulation of the immune system and systemic inflammatory response, reproduction, glucose homeostasis, hematopoiesis, angiogenesis and wound healing. [33][34][35] During states of normal nutrition, the circulating leptin levels are directly correlated with the adipose tissue mass.…”

“…33 Leptin is a hormone/cytokine synthetized by the white adipose tissue, with various functions such as regulation of appetite and energy expenditure via the hypothalamic effects on satiety, in addition to regulation of the immune system and systemic inflammatory response, reproduction, glucose homeostasis, hematopoiesis, angiogenesis and wound healing. [33][34][35] During states of normal nutrition, the circulating leptin levels are directly correlated with the adipose tissue mass. 36 The biological effects of leptin are mediated through the activation of its various receptors expressed in the brain and peripheral tissues such as pancreas, liver, adipose tissue and immune cells (neutrophils, monocytes, macrophages, subpopulations of T and B cells, mast cells, dendritic cells and natural killer cells).…”

“…36 The biological effects of leptin are mediated through the activation of its various receptors expressed in the brain and peripheral tissues such as pancreas, liver, adipose tissue and immune cells (neutrophils, monocytes, macrophages, subpopulations of T and B cells, mast cells, dendritic cells and natural killer cells). 33,36 One of the six isoforms of the leptin receptor (Ob-R) is secreted in plasma and serves as a leptin-binding protein. 33 Leptin circulates both as a biologically active free form and a presumably inactive form bound to plasma proteins and secreted receptor isoform (Ob-Re).…”

Antioxidant and Anti-inflammatory Activities of a Commercial Noni Juice revealed by Carrageenan-induced Paw Edema

“…Endothelin-1, firstly described in endothelial cells and in vascular smooth muscle cells, was demonstrated to play a pivotal role in inflammation in several human diseases, by stimulating production of reactive oxygen species (Elisa et al 2015, Kowalczyk et al 2015. Leptin, produced mainly by the white adipose tissue, plays important roles in the activation of the immune system, and it is a mediator of inflammation (Gualillo et al 2000, Fernández-Riejos et al 2010, Paz-Filho et al 2012.…”

Metabolic risk factors in obesity and diabetes mellitus: implications in the pathogenesis and therapy

“…Leptin alongwith monocytes induces the rele ase of pro-inflammatory cytokines such as TNF-a or IL-6 as well as CCL2 and VEGF [40]. Leptin helps to maintain a chronic inflammatory state in obesity as its synthesis and release is regulated by the pro-inflammatory cytokines [41].…”