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The Role of the Adipokine Leptin in Immune Cell Function in Health and Disease.
Kiernan, K, MacIver, NJ
Frontiers in immunology. 2020;:622468
Abstract
Leptin is a critical mediator of the immune response to changes in overall nutrition. Leptin is produced by adipocytes in proportion to adipose tissue mass and is therefore increased in obesity. Despite having a well-described role in regulating systemic metabolism and appetite, leptin displays pleiotropic actions, and it is now clear that leptin has a key role in influencing immune cell function. Indeed, many immune cells have been shown to respond to leptin directly via the leptin receptor, resulting in a largely pro-inflammatory phenotype. Understanding the role of adipose-tissue derived mediators in inflammation is critical to determining the pathophysiology of multiple obesity-associated diseases, such as type 2 diabetes, autoimmune disease, and infection. This review, therefore, focuses on the latest data regarding the role of leptin in modulating inflammation.
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Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.
Pietrzyk, L, Torres, A, Maciejewski, R, Torres, K
Asian Pacific journal of cancer prevention : APJCP. 2015;(10):4161-8
Abstract
Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).
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3.
Interrelationship between bone turnover markers, calciotropic hormones and leptin in obese Saudi children.
Saber, LM, Mahran, HN, Baghdadi, HH, Al Hawsawi, ZM
European review for medical and pharmacological sciences. 2015;(22):4332-43
Abstract
OBJECTIVE Fat-bone relationship involves the interaction among endocrine, inflammatory, immune processes and bone turnover. We tried to assess the association between Leptin and bone turnover markers (OCN, β-CTx, ALP), calciotropic hormones PTH and 25(OH)D in obese Saudi children. PATIENTS AND METHODS A cross-sectional study performed with 60 obese children and 36 lean children. For all subjects, OCN, ALP, β-CTx, PTH, 25(OH)D, leptin, Ca and Pi were investigated. Levels of leptin were measured by [ELISA] method, and OCN, β-CTx, PTH and 25-(OH)D by an electrochemiluminescence immunoassay. RESULTS Sixty obese Saudi children had means weight (38.3 vs. 13.8 kg), height (121.0 vs. 91.8 cm) leptin (23.04 vs.16.88 ng/ml), PTH (31.5 vs. 14.7 pg/ml), Pi (1.67 vs. 1.54 mmol/l) were significantly higher and 25(OH)D (21.02 vs. 29.45 ng/ml) was significantly lower than controls. There was no difference in serum OCN, β-CTx, ALP and calcium between groups (p > 0.05). In the correlation study, OCN were significantly positively correlated with height, ALP, age, PTH, and β-CTx (r = 0.347, 0.32, p < 0.05), (r = 0.35, 0.51, 0.66, p < 0.01 respectively), while serum 25(OH)D was negatively correlated with PTH, weight, height and BMI (r = -0.45, -0.55, -0.55, -0.47, p < 0.01 respectively). PTH was positively correlated with leptin and β-CTx (r = 0.41, 0.44, p < 0.01), but not to ALP and BMI percentile. β-CTx correlated significantly positive with Pi (r = 0.34 p < 0.05) and ALP with BMI percentile (r = 0.42, p < 0.05). Multiple regression analysis demonstrated that PTH was predicted by leptin and β-CTx (R2 = 0.55); β-CTx by leptin and OCN (R2 = 0.498); OCN by PTH and β-CTx (R2 = 0.47); and 25(OH)D by PTH (R2 = 0.21). CONCLUSIONS The obese children had increased levels of leptin and PTH with strong associated with bone turn over markers OCN, β-CTx and deficiency of 25(OH)D which may be playing an important role in the pathogenesis of obesity and related bone metabolic risk diseases as osteoporosis and fractures.
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[Novel adipokines: their potential role in the pathogenesis of obesity and metabolic disorders].
Korek, E, Krauss, H
Postepy higieny i medycyny doswiadczalnej (Online). 2015;:799-810
Abstract
Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose tissue has become the subject of intensive research. These studies contributed to the discovery that adipocytes have the ability to synthesize and secrete biologically active substances called "adipokines". Adipokines include a variety of cytokines, peptide hormones and enzymes that play a role in a wide variety of biological functions. For example, they are involved in the regulation of appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory and immune processes and play a role in the metabolism of carbohydrates and fats. In obese patients, the secretion of adipokines is frequently abnormal. These changes may predispose to the development of insulin resistance, hypertension and inflammation. Therefore, adipokines are the subject of ongoing clinical trials. The family of adipokines is increasing by the newly discovered peptides. This paper presents the current state of knowledge about retinol binding protein 4 (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP-4), irisin and their potential role in the pathogenesis of metabolic disorders associated with obesity. The knowledge of the role of newly discovered adipokines may help in the treatment of metabolic syndrome.
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Leptin-based adjuvants: an innovative approach to improve vaccine response.
White, SJ, Taylor, MJ, Hurt, RT, Jensen, MD, Poland, GA
Vaccine. 2013;(13):1666-72
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Abstract
Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥30 kg/m(2)) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin's role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants.
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Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension.
Sonmez, A, Kisa, U, Uckaya, G, Eyileten, T, Comert, B, Koc, B, Kocabalkan, F, Ozata, M
Journal of the renin-angiotensin-aldosterone system : JRAAS. 2001;(2):112-6
Abstract
Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9+/-7.6 years, range 23-49 years, BMI; 27.6+/-3.7kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.