leptin and Immune-System-Diseases

White adipose tissue (WAT) is a specialized tissue whose main function is lipid synthesis and triglyceride storage. It is now considered as an active organ secreting a plethora of hormones and cytokines namely adipokines. Discovered in 1994, leptin has emerged as a key molecule with pleiotropic functions. It is primarily recognized for its role in regulating energy homeostasis and food intake. Currently, further evidence suggests its potent role in reproduction, glucose metabolism, hematopoiesis, and interaction with the immune system. It is implicated in both innate and adaptive immunity, and it is reported to contribute, with other adipokines, in the cross-talking networks involved in the pathogenesis of chronic inflammation and immune-related diseases of the musculo-skeletal system such as osteoarthritis (OA) and rheumatoid arthritis (RA). In this review, we summarize the most recent findings concerning the involvement of leptin in immunity and inflammatory responses in OA and RA.

Topics: Adipokines; Arthritis, Rheumatoid; Humans; Immune System Diseases; Inflammation; Leptin; Osteoarthritis

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 immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.

Topics: Adaptive Immunity; Animals; Arthritis, Rheumatoid; Humans; Immune System Diseases; Immunity, Innate; Inflammation; Killer Cells, Natural; Leptin; Neutrophils; Osteoarthritis; Receptors, Leptin

Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody-related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated.

Topics: Abortion, Habitual; Cell-Derived Microparticles; Chorionic Gonadotropin; Endocrine System Diseases; Female; Glycodelin; Glycoproteins; Humans; Immune System Diseases; Leptin; Polymorphism, Genetic; Pregnancy; Risk Factors; Uterine Diseases; Uterus

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. Since its discovery in 1994, leptin has attracted increasing interest in the scientific community for its pleiotropic actions. One of these functions is the relationship between nutritional status and immune competence. It structurally resembles proinflammatory cytokines, such as IL-6 and IL-12. The cytokine-like structural characteristic of leptin is implicative of its function in regulating immune responses. The role of leptin in regulating immune responses has been assessed in vitro as well as in clinical studies. It has been shown that disease conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders, such as autoimmune diseases, are associated with the increased secretion of leptin and the production of proinflammatory pathogenic cytokines. In this paper, we review the most recent advances of the role of leptin in immune-rheumatological diseases, and we discuss whether strategies aimed at modifying leptin levels could represent innovative and therapeutic tools for autoimmune disorders.

Topics: Cytokines; Humans; Immune System Diseases; Immunomodulation; Inflammation Mediators; Leptin; Rheumatology; Structural Homology, Protein

PLeptin is an adipocyte-derived hormone with pleiotropic effects on energy homeostasis, endocrine and reproductive functions, and immune responses. The multiple actions of leptin have led to the design and development of several leptin-based approaches to modulate the metabolic and endocrine status, to reduce inflammation, and to improve immune responses. Here, we review the current patents on leptin in different clinic applications.

Topics: Animals; Biomimetics; Genetic Therapy; Humans; Immune System Diseases; Immunization; Infertility; Leptin; Metabolic Diseases; Neoplasms; Patents as Topic

Treatment of obesity and its associated immune mediated diseases is challenging due to impaired function of leptin system. Thus leptin is providing an interesting target for therapeutic intervention. Leptin, an adipose tissue-derived adipokine, displays a variety of immune functions, and regulate both innate and adaptive immune responses. The increased secretion of leptin (hyperleptinemia) and production of proinflammatory cytokines has been implicated in the pathogenesis of obesity-related immune diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer, systemic lupus erythematosus, rheumatoid arthritis, crohn's disease and multiple sclerosis. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carries a degree of risk, is time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need of an alternative approach for the management of immune dysfunction associated with obesity and its related diseases. For the aforementioned diseases that are related to leptin overabundance, new drugs blocking leptin signaling need to be generated. The research on the discovery of clinically important novel compounds from natural source is expanding due to their safety and no side effect. The fungal endophytes are the microbes that colonize internal tissue of plants without causing negative effects to the host. They produce plethora of substances of potential use to modern medicinal and pharmaceutical industry. The increasing body of evidence associated with application of bioactive metabolites derived from fungal endophytes in diverse disease states merits its use as therapeutic drugs. In particular, the saponins have been extensively proved to modulate the immune system, which has raised a significant interest in their potential as immunomodulators. Thus, our hypothesis is that the saponins derived from fungal endophytes can be explored as clinical applicable leptin inhibitors for treating immune mediated diseases.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Cytokines; Endophytes; Fungi; Humans; Immune System; Immune System Diseases; Immunologic Factors; Immunotherapy; Inflammation; Leptin; NF-kappa B; Obesity; Translational Research, Biomedical