leptin and Rheumatic-Diseases

In the last two decades, white adipose tissue (WAT) has been recognized as a key actor of many physiological and pathological conditions. WAT is able to produce mediators, named "adipokines", which may affect systemic homeostasis. In particular, leptin is not only involved in appetite and energy metabolism, but also in immune system. Increasing evidence established that leptin can regulate both innate and adaptive immunity mainly with pro-inflammatory effects but also, to a lesser extent, with anti-inflammatory features. In autoimmune diseases, a failure or breakdown of the mechanisms of self-tolerance is observed. Leptin, which plays an important role in the control of immune balance, has been involved in autoimmunity generation and maintenance. In this review, it has been provided an up-to-date report about the role of leptin in systemic autoimmune diseases, with particular reference to connective tissue diseases, inflammatory arthritis, and vasculitis.

Topics: Adaptive Immunity; Adipose Tissue, White; Animals; Biomarkers; Cytokines; Energy Metabolism; Gene Expression Regulation; Humans; Immunity, Innate; Leptin; Rheumatic Diseases

The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

Topics: Adipokines; Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Metabolic Syndrome; Nicotinamide Phosphoribosyltransferase; Resistin; Rheumatic Diseases

A large body of evidence from clinical and experimental studies is aiding to understand the close relationships between obesity and rheumatic diseases. For instance, it is generally accepted that obesity contributes to the development of osteoarthritis by increasing mechanical load of the joints, at least in weight bearing joints. However, besides mechanical effects, recent studies demonstrated that white adipose tissue is able to secrete a plethora of soluble factors, called adipokines, which have a critical role in the development and progression of some rheumatic diseases such as osteoarthritis and rheumatoid arthritis. In this article, we summarize the recent findings on the interaction of certain adipokines with the two most common rheumatic diseases: osteoarthritis and rheumatoid arthritis.

Topics: Adipokines; Adiponectin; Animals; Arthritis, Rheumatoid; Humans; Leptin; Osteoarthritis; Rheumatic Diseases

Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications.

Topics: Adipokines; Adiponectin; Animals; Atherosclerosis; Cardiovascular Diseases; Humans; Leptin; Rheumatic Diseases

Topics: Adipokines; Adiponectin; Adiposity; Cardiovascular Diseases; Humans; Leptin; Rheumatic Diseases

Important advances in our understanding of the relationships between adipokines, inflammation and the immune response have been achieved in the past 10 years. White adipose tissue has emerged as a highly dynamic organ that releases a plethora of immune and inflammatory mediators that are involved in numerous diseases, including not only rheumatic diseases such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus, but also cardiovascular and metabolic complications that are frequently observed in rheumatic diseases. Our rapidly growing knowledge of adipokine biology is revealing the complexity of these amazing proteins, thereby redefining white adipose tissue as a key element of the inflammatory and immune response in rheumatic diseases. Adipokines exert potent modulatory actions on target tissues and cells involved in rheumatic disease, including cartilage, synovium, bone and various immune cells. In this Review, we describe the most recent advances in adipokine research in the context of rheumatic diseases, focusing primarily on leptin, adiponectin, visfatin and resistin, and also the potential role of newly identified adipokines such as chemerin, lipocalin 2 and serum amyloid A3.

Topics: Adipokines; Adiponectin; Animals; Disease Models, Animal; Humans; Leptin; Rheumatic Diseases

Leptin is a 16 kDa adipocyte-secreted hormone that regulates weight centrally and links nutritional status with neuroendocrine and immune function. Since its cloning in 1994, leptin's role in regulating immune and inflammatory response has become increasingly evident. Actually, the increase of leptin production that occurs during infection and inflammation strongly suggests that leptin is a part of the cytokines loop which governs the inflammatory-immune response and the host defence mechanism. Indeed, leptin stimulates the production of pro-inflammatory cytokines from cultured monocytes and enhances the production of Th1 type cytokines from stimulated lymphocytes. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions such as type 1 diabetes, rheumatoid arthritis and chronic bowel disease. Obesity is characterized by elevated circulating leptin levels which might contribute significantly to the so called low-grade systemic inflammation, making obese individuals more susceptible to the increased risk of developing cardiovascular diseases, type II diabetes or inflammatory articular degenerative disease such as osteorathritis (OA). As a matter of fact, a key role for leptin in OA has been recently demonstrated since leptin exhibits, in synergy with other pro-inflammatory cytokines, a detrimental effect on articular cartilage cells by promoting nitric oxide synthesis. This review will focus prevalently on the complex relationships existing among leptin, inflammatory response and immunity, trying to provide surprising insights into leptin's role and to discuss challenges and prospects for the future.

Topics: Animals; Humans; Immunity, Cellular; Immunologic Factors; Inflammation Mediators; Leptin; Receptors, Cell Surface; Receptors, Leptin; Rheumatic Diseases

To investigate obesity as susceptibility factor in patients with idiopathic AA amyloidosis.. Clinical, biochemical and genetic data were obtained from 146 patients with AA amyloidosis. Control groups comprised 40 patients with long-standing inflammatory diseases without AA amyloidosis and 56 controls without any inflammatory disease.. Patients with AA amyloidosis had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases as underlying inflammatory disease (n = 111, median age 46 years). However, in a significant proportion of patients with AA amyloidosis no primary disease was identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic AA amyloidosis were more obese and older than patients with AA amyloidosis secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of more than 30 µg/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in 40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1 polymorphism was confirmed as a susceptibility factor for AA amyloidosis irrespective of the type of the disease.. Obesity, age and the SAA1 polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent advances in treatment of FMF and rheumatic disorders will decrease the incidence of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an emerging problem in the ageing and increasingly obese population.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Familial Mediterranean Fever; Female; Genetic Predisposition to Disease; Humans; Leptin; Male; Middle Aged; Obesity; Polymorphism, Genetic; Rheumatic Diseases; Serum Amyloid A Protein

Topics: Animals; Autoimmune Diseases; Humans; Leptin; Rheumatic Diseases

Authors discuss the musculoskeletal aspects of obesity by applying a novel approach. Biochemical changes associated with obesity and especially metabolic syndrome, may have a great impact on the function of bones, joints and muscles. Therefore we need a new view and new strategies in rheumatic diseases. Obesity-associated metabolic changes should be considered during the progress of as well as the selection of treatment in inflammatory rheumatic diseases. Individualised treatment is necessary due to associated comorbidities as well. Orv Hetil. 2019; 160(44): 1727-1734.. Absztrakt: A szerzők az elhízás mozgásszervi vonatkozásait új megközelítésben, elsősorban annak metabolikus hatásait kiemelve ismertetik. Az elhízással és különösen a metabolikus szindrómával járó biokémiai változások megváltoztatják a csont, az ízületi struktúrák és az izomzat működését. Ezek alapján szemléletváltozás szükséges bizonyos kórképekben az eddig kialakult nézetekben. A gyulladásos reumatológiai betegségek lefolyásának súlyosságában és az alkalmazott kezelések megválasztásában is figyelembe kell venni az elhízással járó anyagcsere-változásokat. A társuló komorbiditások miatt a személyre szabott kezelés fontossága kiemelt jelentőségű. Orv Hetil. 2019; 160(44): 1727–1734.

Topics: Adipokines; Arthritis; Humans; Joint Diseases; Leptin; Metabolic Syndrome; Musculoskeletal Diseases; Obesity; Osteoarthritis; Rheumatic Diseases