Leptin, a railroad switch enabling crossover signals among inflammation, immunity and metabolism (original) (raw)
Related papers
2010
white adipose tissue is currently considered as an active endocrine organ that secretes a plethora of factors named adipokines, some of them being of pro-inflammatory na-ture that likely contribute to the low-level systemic inflammation, a status that is often present in metabolic syndrome-associated chronic pathologies such as obesity, type 2 diabetes, and atherosclerosis. Leptin is historically indisputably one of the most im-portant adipokine secreted by fat cells, with a variety of physiological roles ranging from to the control of metabolism, energy homeostasis and inflammatory response to cognition. Leptin is also implicated in the connection between nutritional status and immune competence, modulating both the innate and adaptive immune responses in normal as well as pathological conditions. it has been shown that conditions char-acterized by low leptin levels are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune dise...
Leptin in the interplay of inflammation, metabolism and immune system disorders
Nature reviews. Rheumatology, 2017
Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including im...
Leptin: Role of metabolism in the regulation of inflammation
Biomed Rev, 2006
Over the last few years the intricate interaction between immune system and adipose tissue has been recognized. Indeed, it has been suggested that adipose tissue is not only a mere site of lipid and energy storage but can be considered as an "immunerelated" organ producing a series of molecules named adipokines. Among these, leptin, an adipocyte-derived cytokine-like hormone, seems to play a pivotal role in the regulation of several neuroendocrine and immune functions. In this review, we describe the effects of leptin in inflammation and immunity, and speculate on the possible modulation of the leptin axis in novel adipopharmacotherapeutic settings.
Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications
Arquivos Brasileiros de Endocrinologia & Metabologia, 2012
Leptin, 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 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
Role of Leptin in the Activation of Immune Cells
Mediators of Inflammation, 2010
Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated diso...
Obesity, Fat Mass and Immune System: Role for Leptin
Frontiers in physiology, 2018
Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.
2010
Leptin, an adipocyte-secreted peptide, has a dual role acting as hormone in central regulation of metabolism and energy homeostasis, and as cytokine to regulate the innate and adaptive immune response in normal and pathological conditions. This review provides a synopsis of recent advances regarding the emerging role of leptin as a modulator of inflammatory and immune responses in adipose tissue in obesity. Scientific databases (Medline and PubMed) have been used to acquire the most recent and valuable reports about this issue. Recent findings indicate that leptin in adipose tissue acts to promote adipogenesis and angiogenesis processes, to enhance proliferation and production of pro-inflammatory cytokines by T-cells, macrophages and dendritic cells, and to negatively regulate the proliferation and expansion of regulatory T-cells, a specific lymphocytes subset involved in the control of immune responses. New therapeutic strategies based on developing leptin- or leptinreceptor neutra...
Current Immunology Reviews, 2008
The past few years of research on leptin have provided important information on the link between metabolism and immune homeostasis. Adipocytes influence not only the endocrine system but also the immune response through several cytokine-like mediators known as adipokines, which include leptin. It is widely accepted that leptin can directly link nutritional status and pro-inflammatory T helper 1 immune responses, and that a decrease of leptin plasma concentration during food deprivation can lead to an impaired immune function. Additionally, several studies have implicated leptin in the pathogenesis of chronic inflammation, and the elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, type II diabetes, or degenerative disease including autoimmunity and cancer. Conversely, reduced levels of leptin such as those found in malnourished individuals have been linked to increased risk of infection and reduced cell-mediated immune responses. We discuss here the functional influences of leptin in the physiopathology of inflammation, and the effects of leptin in the modulation of such responses.
Leptin, a new “godfather” in the cytokines super “family”
The elevate prevalence of obesity and obesity-related diseases drew an increasing interest over the last 10 years on white adipose tissue and its secretory products, being the discovery of leptin in 1994 the trigger of the renaissance of the studies about adipose tissue. Leptin was initially depicted as the most important anorexigenic factor with neuroendocrine actions, but it has been later shown to regulate significantly also immune and inflammatory processes. Truly, leptin is a dual molecule: apart from its previously envisaged actions, increasing evidence frames leptin as a novel pro-inflammatory adipokine and it is at present considered the link among immune system, inflammatory response and neuroendocrine system. Leptin is able to regulate and participate both in immune homeostasis and inflammatory processes by acting as a modulator of cell activity and playing an active role in articular degenerative inflammatory diseases such as osteoarthritis and rheumatoid arthritis but also in a host of autoimmune inflammatory conditions such as encephalomyelitis, type 1 diabetes, and bowel inflammation. This review has been focussed more on the cytokine facet of leptin, even though its role as metabolic hormone has been also addressed.