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1.
Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk.
Landecho, MF, Tuero, C, Valentí, V, Bilbao, I, de la Higuera, M, Frühbeck, G
Nutrients. 2019;(11)
Abstract
Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
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2.
Interaction between genes involved in energy intake regulation and diet in obesity.
Crovesy, L, Rosado, EL
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:110547
Abstract
Obesity is a multifactorial, complex, and public health problem worldwide. Interaction between genes and environment as associated with diet may predispose an individual to obesity. In this sense, nutrigenetics appears to be a strategy that can improve understanding of the gene-diet interaction. The aim of this literature review was to summarize data from studies of genes involved in the regulation of energy intake (melanocortin 4 receptor [MC4R], fat mass and obesity-associated [FTO], ghrelin [GHRL], leptin [LEP], and cholecystokinin [CCK]) and diet interaction in obesity. The presence of polymorphisms in MC4R, FTO, leptin, and the respective receptor appear to be associated with higher energy and total lipid consumption. Polymorphisms in FTO, leptin, and leptin receptor are also related to increased intake of saturated fatty acids. Individuals with the MC4R, FTO, and ghrelin polymorphisms, who submitted themselves for weight loss intervention, appeared to achieve weight loss similar to individuals without polymorphisms in these genes. Additionally, protein seems to interact with these genes, which increases or decreases appetite, or to drive or lessen body weight recovery. Additionally, polymorphisms in these genes were found to be associated with inappropriate eating behaviors, such as increased consumption of sweets and snacks, consumption of large food portions, desire to eat, and eating associated with emotional issues. Preliminary data has supported the gene-diet interaction in determining weight loss and gain in individuals with polymorphisms in the genes involved in energy intake. Despite the advent of nutrigenetics in obesity, it is still too early to define the dietary management for weight loss based on the presence or absence of obesity polymorphisms.
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3.
Leptin, Obesity, and Leptin Resistance: Where Are We 25 Years Later?
Izquierdo, AG, Crujeiras, AB, Casanueva, FF, Carreira, MC
Nutrients. 2019;(11)
Abstract
Leptin, a hormone that is capable of effectively reducing food intake and body weight, was initially considered for use in the treatment of obesity. However, obese subjects have since been found to have high levels of circulating leptin and to be insensitive to the exogenous administration of leptin. The inability of leptin to exert its anorexigenic effects in obese individuals, and therefore, the lack of clinical utility of leptin in obesity, is defined as leptin resistance. This phenomenon has not yet been adequately characterized. Elucidation of the molecular mechanisms underlying leptin resistance is of vital importance for the application of leptin as an effective treatment for obesity. Leptin must cross the blood-brain barrier (BBB) to reach the hypothalamus and exert its anorexigenic functions. The mechanisms involved in leptin transportation across the blood-brain barrier continue to be unclear, thereby preventing the clinical application of leptin in the treatment of obesity. In recent years, new strategies have been developed to recover the response to leptin in obesity. We have summarized these strategies in this review.
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4.
Association of circulating resistin, leptin, adiponectin and visfatin levels with Behçet disease: a meta-analysis.
Lee, YH, Song, GG
Clinical and experimental dermatology. 2018;(5):536-545
Abstract
BACKGROUND Behçet disease (BD) is a chronic inflammatory disease. Adipokines are synthesized in adipose tissue, and have been reported to play important roles in the pathogenesis of autoimmune and inflammatory diseases, including BD. AIM: To evaluate the relationship between circulating blood adipokine levels and BD. METHODS We conducted a meta-analysis of papers reporting on serum/plasma resistin, leptin, adiponectin and visfatin levels in patients with BD and in healthy controls (HCs). We identified 82 relevant studies using electronic and manual search methods, and selected 16 studies for full-text review based on the title and abstract. Two of these were later excluded (one was a review, one had no data), leaving 14 articles that met the inclusion criteria for this meta-analysis. RESULTS The 14 included studies assessed 637 patients with BD and 520 HCs. Compared with the HCs, the BD group had significantly higher levels of leptin [standardized mean difference (SMD) = 0.68, 95% CI 0.15-1.21, P = 0.01]. Levels of resistin (SMD = 0.51, 95% CI 0.92-0.918, P = 0.02) and adiponectin (SMD = 0.31, 95% CI 0.06-0.56, P = 0.02) were significantly higher in the BD group after adjustment for age, sex and body mass index (BMI), but not without such adjustment (resistin: (SMD = 0.38, 95% CI -0.18 to 0.93, P = 0.19; adiponectin: SMD = -0.59, 95% CI -2.23 to 1.06, P = 0.48). A significantly lower visfatin level was found in the BD group with adjustment (SMD = -1.70, 95% CI -2.14 to -1.25, P < 0.001) but not without adjustment (SMD = 0.31, 95% CI -0.21 to 0.82, P = 0.24). CONCLUSIONS Our meta-analysis revealed significantly higher circulating resistin, leptin and adiponectin levels and lower visfatin levels in patients with BD than in HCs, indicating that adipokines probably play an important role in BD pathogenesis.
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5.
Leptin, An Adipokine With Central Importance in the Global Obesity Problem.
Mechanick, JI, Zhao, S, Garvey, WT
Global heart. 2018;(2):113-127
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Abstract
Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases.
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Appetite hormones in children and adolescents with cancer: a systematic review of observational studies.
Fayh, APT, Bezerra, ADL, Friedman, R
Nutricion hospitalaria. 2018;(1):201-210
Abstract
INTRODUCTION Malnutrition in children with cancer is a significant risk factor for negative outcomes, but in the clinical practice setting, it is difficult to pinpoint which factors operate to cause substantial weight loss and malnutrition in a given patient. Appetite-related hormones like ghrelin and leptin are among possible mediators. However, only few studies have examined the role of these hormones in pediatric patients with cancer to date. Thus, the purpose of this study was to systematically review possible changes in the levels of appetite hormones, specially leptin and ghrelin, in pediatric patients with cancer. MATERIAL AND METHODS We systematically reviewed the literature using PubMed, Lilacs and Scielo, as well as manual bibliographical reference search of the studies. According to the Medical Subject Headings of the National Library of Medicine (MeSH), "childhood cancer", "ghrelin" and "leptin" were used as descriptors. RESULTS Fifteen studies were included in this systematic review published in English, from 2000 to 2015. A total of 863 patients were evaluated, ages ranging from 0 to 21 years, and most of the studies reported on children and adolescents with acute lymphoblastic leukemia (ALL) survivors. Most studies analyzed leptin levels; only two studies evaluated levels of ghrelin. CONCLUSION This review confirms that changes in the responses of the ghrelin and leptin hormones in children and adolescents with cancer are quite diverse, probably due to the different types of cancer observed, different treatments performed and biological characteristics of this age group.
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The effect of L-carnitine supplementation on serum leptin concentrations: a systematic review and meta-analysis of randomized controlled trials.
Nazary-Vannani, A, Ghaedi, E, Mousavi, SM, Teymouri, A, Rahmani, J, Varkaneh, HK
Endocrine. 2018;(3):386-394
Abstract
PURPOSE The actual effects of L-carnitine administration on leptin serum level is inconsistent. In order to assess the efficacy of L-carnitine supplementation on serum leptin we conducted a meta-analysis of randomized controlled trials (RCTs). METHODS Seven studies with 325 cases and 330 controls were included. The pooled weighted mean difference (WMD) was calculated by random-effects model. The heterogeneity across studies was evaluated by using Cochrane's Q and I2 tests. In addition, we carried out the metaninf command to test the effect of each individual study on the overall result. RESULTS L-carnitine supplementation seemed to have no significant effect on serum leptin concentrations (WMD: -0.565 ng/mL; 95% CI: -2.417 to 1.287, p = 0.550). However, between-study heterogeneity was higher across all studies (I2 = 84.3%, p < 0.0001). Subgroup analysis to find the sources of heterogeneity showed that L-carnitine dosage (g) ( < 2 g: I2 = 00.0%, p = 0.408), and study population (diabetes: I2 = 46.7%, p = 0.153, and non-diabetes: I2 = 15.1%, p = 0.317) were the potential sources of heterogeneity. Besides, a more significant reduction in serum leptin concentration was observed with a daily dose of ≥ 2 mg L-carnitine (WMD: -2.742 ng/mL; 95% CI: -3.039 to -2.444, p < 0.001), in diabetic patients (WMD: -2.946 ng/mL; 95% CI: -3.254 to -2.638, p < 0.001), and with intervention duration <12 weeks (WMD: -2.772 ng/mL; 95% CI: -3.073 to -2.471, p < 0.001). CONCLUSION L-carnitine consumption does not reduce serum leptin significantly. However, a significant effect on leptin was observed in diabetic patients and patients who received doses more than 3 mg per day in the course of <12 weeks.
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Effect of green tea on plasma leptin and ghrelin levels: A systematic review and meta-analysis of randomized controlled clinical trials.
Haghighatdoost, F, Nobakht M Gh, BF, Hariri, M
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:17-23
Abstract
OBJECTIVE The purpose of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea on serum leptin and ghrelin concentrations. METHODS We searched PubMed, ISI Web of Science, Scopus, and Google scholar databases up to December 2016. The searches included RCTs conducted in human adults, and studies on the effect of green tea and green tea extract on serum leptin and ghrelin concentrations as outcome variables. Weighted mean differences (WMDs) and standard errors (SEs) of changes in serum ghrelin and leptin levels were calculated. The random effects model was used to derive the summary mean estimates with their corresponding SEs. RESULTS Eleven RCTs were eligible to be included in the systematic review and the meta-analysis. Our analysis indicated that green tea did not significantly affect leptin and ghrelin concentrations in comparison to placebo (WMD = 1.28 ng/mL, 95% confidence interval: -0.49 to 3.05; P = 0.156, and WMD = 21.49 pg/mL, 95% confidence interval: -40.86 to 83.84; P = 0.499, respectively). However, green tea was associated with an increase in leptin concentration in studies that lasted for more than 12 wk and an increase in ghrelin in women and non-Asians. CONCLUSIONS Green tea or green tea extract might not be able to change circulatory leptin and ghrelin levels, especially with short-term interventions. More RCTs with longer duration of treatment and higher doses are necessary to assess green tea's effect on fat mass and obesity hormones.
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9.
Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.
Packer, M
Circulation. 2018;(15):1614-1631
Abstract
Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits.
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10.
Effect of Conjugated Linoleic Acid Supplementation on Serum Leptin Concentration: A Systematic Review and Meta-Analysis.
Haghighatdoost, F, Hariri, M
Endocrine, metabolic & immune disorders drug targets. 2018;(3):185-193
Abstract
BACKGROUND There are controversies regarding the effect of conjugated linoleic acid (CLA) on serum leptin. OBJECTIVE To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of CLA on serum leptin concentrations. METHOD Databases such as Ovid, PubMed/Medline, SCOPUS, Google Scholar, and ISI databases up to January 2017 were searched. The searches included RCTs conducted among human adults, and studies on the effect of conjugated linoleic acid on serum leptin concentrations as outcome variables. The mean difference and standard deviation of leptin changes in the intervention and control groups were used as effect size measures for the meta-analysis. RESULT Eleven trials with thirteen effect sizes were pooled in this meta-analysis. CLA supplementations could not reduce serum leptin levels significantly (-0.12 (ng/ml); 95% CI: -1.29, 1.05; P=0.837). However, the impact of CLA supplementation differed by sex and BMI status. Compared with the control group, CLA administration reduced serum leptin levels significantly in trials conducted among male (- 0.86 (ng/ml); 95% CI: -1.11, -0.62; P<0.0001) or overweight individuals (-1.37 (ng /ml); 95% CI: -2.55, -0.20; P=0.022) and lasted for less than 8 weeks (-0.90 (ng/ml); 95% CI: -1.64, -0.17; P=0.0.016). CONCLUSION CLA supplementation might be able to decrease circulating leptin levels in studies with duration of less than 8 weeks especially among male and overweight subjects. Additional RCTs that are well controlled for energy intakes may be necessary to explain the cause of short- and long-term effects of conjugated linoleic acid. The protocol was registered with PROSPERO (No. CRD42017059165).