scholarly journals Leptin and Obesity: Role and Clinical Implication

2021 ◽  
Vol 12 ◽  
Author(s):  
Milan Obradovic ◽  
Emina Sudar-Milovanovic ◽  
Sanja Soskic ◽  
Magbubah Essack ◽  
Swati Arya ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Body Mass ◽  
Animal Studies ◽  
Leptin Receptor ◽  
Reproductive Function ◽  
Peptide Hormone ◽  
Feedback Mechanism ◽  
Leptin Resistance ◽  
Total Body Mass ◽  
Negative Feedback Mechanism

The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese (ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin’s pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.

P3482Leptin, receptor to leptin and expression in adipocytes isolated from different adipose depots in patients with ischemic heart disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y A Dyleva ◽  
O Gruzdeva ◽  
E Uchasova ◽  
E Belik ◽  
N Brel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Heart Disease ◽  
Leptin Receptor ◽  
Artery Bypass ◽  
Leptin Resistance ◽  
Protective Mechanism ◽  
Negative Dependence ◽  
Soluble Receptor ◽  
High Concentration ◽  
Magnetic Resonance Imaging Mri

Abstract Purpose To study the peculiarities of the content of leptin and the leptin receptor in adipocyte culture of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue and the expression of their genes. Methods 29 patients with coronary heart disease were examined. Adipocytes were isolated from SAT, EAT and PVAT samples obtained during coronary artery bypass grafting, followed by evaluation (after 24 hours) of the leptin concentration (Human resistin ELISA, R&D Systems, USA) and leptin gene expression in cell culture. Magnetic resonance imaging (MRI) was used to determine the area of the visceral (VAT) and subcutaneous adipose tissue (SAT) of the abdominal region, the thickness of epicardial adipose tissue (EAT). The calculation of the free leptin index (FLI) was determined by the formula: leptin/SOB-R * 100. Leptin resistance was defined as an FLI >0.25. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0. Results In adipocytes of EAT, leptin secretion was 1.2 times higher than in adipocytes of PVAT, which is consistent with the expression of the leptin gene. The content of leptin soluble receptor was opposite in the adipocytes of PVAT higher than in EAT and SAT 2.3 and 3.1 times, respectively. At the same time, the index of free leptin was higher in SAT adipocytes 1.3 and 3.2 times in comparison with EAT and PVAT. The correlation analysis confirmed the relationship between EAT thickness and the serum concentrations of leptin. Thus, in patients with VO, the leptin concentration had a negative dependence on the thickness of the left and right ventricle (r=−0.28, p=0.02; r=−0.33, p=0.02, respectively). A negative dependence on the EAT thickness was also established for the FLI (r=−0.28; p=0.03). PVAT of the abdominal aorta is similar to the properties of visceral AT. An analysis of the possible relationship between perivascular adipocytes and adipokine exchange rates showed a direct relationship between the volume PVAT of the abdominal aortic ventricle and leptin (r=0.44, p=0.01), as well as the FLI (r=0.56; p=0.03). Conclusion Adipocytes SAT, EAT and PVAT differed in the level of secretion of leptin. In epicardial and, to a greater extent, in perivascular adipocytes, a protective mechanism against a high concentration of leptin was observed due to increased secretion of the soluble receptor to leptin. The high content of leptin and the low soluble receptor for leptin led to the development of leptin resistance, which was more pronounced in the culture of adipocytes SAT. Meanwhile, the EAT thickness was inversely related to the concentration of leptin and the FLI index (one of the main leptin-resistance markers).

Abstract 25: Angiotensin AT 1A Receptors on Leptin Receptor-Expressing Cells are Required for the Blood Pressure and Metabolic Rate Effects of Leptin

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Justin L Grobe ◽  
Kristin E Claflin
Keyword(s):  
Blood Pressure ◽  
Metabolic Rate ◽  
Body Mass ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Brain Regions ◽  
Leptin Resistance ◽  
Brown Adipose ◽  
Obesity Hypertension ◽  
The Brain

Circulating leptin and the local brain renin-angiotensin system (RAS) both contribute to the control of food intake (FI), resting metabolic rate (RMR) and blood pressure (BP), and both have been postulated to contribute to obesity-hypertension. Here we examined the provocative hypothesis that the brain RAS is required for (or mediates) the RMR- and BP-stimulating effects of leptin. To create animals lacking the AT 1A receptor specifically in cells expressing the leptin receptor (“KO”), mice with a flox’ed version of the endogenous angiotensin AT 1A receptor gene (AT 1A flox ) were crossed with mice expressing cre-recombinase via the leptin receptor promoter (ObR-Cre). Body mass, body composition, blood chemistry, glucose tolerance, and FI behaviors were essentially unchanged through 34 weeks of age in mice maintained on standard chow (Teklad 7013). In contrast, anesthetized BP (MAP; control n=9, 91.6 ± 4.1, vs KO n=8, 78.0 ± 3.7 mmHg) and heart rate (351 ± 13, vs 308 ± 11 BPM) were reduced in KO mice (both P<0.05). Further, interscapular brown adipose (BAT SNA, 112 ± 22, vs 22 ± 35 % above baseline at 3 hr) and renal (154 ± 19, vs 53 ± 23 % above baseline at 3 hr) sympathetic nerve activity responses to acute leptin injection (60 μg, i.v.) were completely abolished (both P<0.05). When maintained on a 45% high fat diet (OpenSource D12451 ) to increase endogenous leptin production, KO mice exhibited accelerated body mass (control n=15, -0.1 ± 0.1, vs KO n=4, +1.7 ± 0.5 g/wk) and fat mass (+2.9 ± 0.5, vs +4.9 ± 1.1 g/5 wk) gains (both P<0.05), likely due to normal FI behaviors but a 18% reduction in RMR (control n=16, 0.196 ± 0.011, vs KO n=7, 0.161 ± 0.004 kcal/hr at 30°C, P<0.05). We conclude that expression of angiotensin AT 1A receptors on leptin-sensitive cells is required for the metabolic rate and cardiovascular effects of leptin. Ongoing studies are focused on identifying the brain regions and subsets of leptin receptor-expressing cells in which this RAS-leptin cross-talk occurs, and the directionality and molecular mediators of this interaction. We hypothesize that uncontrolled or pathological activity of the brain RAS may thus help explain the clinically variable effects of leptin, and contribute to the mechanism(s) of selective leptin resistance and obesity-hypertension.

scholarly journals Mapping of human brown adipose tissue in lean and obese young men

2017 ◽  
Vol 114 (32) ◽  
pp. 8649-8654 ◽  
Author(s):  
Brooks P. Leitner ◽  
Shan Huang ◽  
Robert J. Brychta ◽  
Courtney J. Duckworth ◽  
Alison S. Baskin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Cold Exposure ◽  
Young Men ◽  
Total Body Mass ◽  
Fat Depots ◽  
Increase Glucose Uptake ◽  
Brown Adipose ◽  
Wide Range

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

scholarly journals db/db Mice Exhibit Features of Human Type 2 Diabetes That Are Not Present in Weight-Matched C57BL/6J Mice Fed a Western Diet

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Susan J. Burke ◽  
Heidi M. Batdorf ◽  
David H. Burk ◽  
Robert C. Noland ◽  
Adrianna E. Eder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass ◽  
Leptin Receptor ◽  
Human Obesity ◽  
Total Body Mass ◽  
Islet Size ◽  
Total Body ◽  
Similar Body ◽  
Deficient Mice

To understand features of human obesity and type 2 diabetes mellitus (T2D) that can be recapitulated in the mouse, we compared C57BL/6J mice fed a Western-style diet (WD) to weight-matched genetically obese leptin receptor-deficient mice (db/db). All mice were monitored for changes in body composition, glycemia, and total body mass. To objectively compare diet-induced and genetic models of obesity, tissue analyses were conducted using mice with similar body mass. We found that adipose tissue inflammation was present in both models of obesity. In addition, distinct alterations in metabolic flexibility were evident between WD-fed mice and db/db mice. Circulating insulin levels are elevated in each model of obesity, while glucagon was increased only in the db/db mice. Although both WD-fed and db/db mice exhibited adaptive increases in islet size, the db/db mice also displayed augmented islet expression of the dedifferentiation marker Aldh1a3 and reduced nuclear presence of the transcription factor Nkx6.1. Based on the collective results put forth herein, we conclude that db/db mice capture key features of human T2D that do not occur in WD-fed C57BL/6J mice of comparable body mass.

scholarly journals BODY COMPONENT COMPOSITION AND STRESS-INDUCED FEATURES OF LEPTIN SECRETION IN FEMALES WITH VARIOUS BODY MASS INDEX

2020 ◽  
Vol 20 (2) ◽  
pp. 80-89
Author(s):  
L Smelysheva ◽  
E Musikhina ◽  
N Artenyan ◽  
G Kovaleva ◽  
G Kuznetsov
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Component Composition ◽  
The Body ◽  
Leptin Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Energy Status ◽  
Significant Difference ◽  
Body Component

Aim. The article aims to study the dynamics of the adipose tissue hormone leptin in healthy females with different body component composition and body mass index to assess their energy status under stress. Materials and methods. Based on anthropometry and bioimpedancemetry, three groups of girls were formed: the first group included girls with a BMI of less than 18.5 kg/m2, body mass deficiency (BMD), the second – from 18.5 to 24.9 kg/m2, normal body mass (NBM), the third – with a BMI of more than 24.9 kg/m2, which corresponds to overweight (OvBM). The body component composition was determined by bioimpedancemetry. Plasma leptin concentration was evaluated by enzyme-linked immunosorbent assay both in normal conditions and during emotional stress. Results. In the selected subgroups, a significant difference in the body component composition was found with an increase in the series of BMD → NBM → OvBM. When assessing the level of metabolic processes by the magnitude of the phase angle, it was found that 3.41% of females with BMD showed signs of increased protein catabolism. The stress-induced dynamics of the hormone leptin was evaluated. In normal conditions, the concentration of leptin in blood plasma positively correlated with BMI and depended on the component composition of the body. Conclusion. In persons with BMD, the adipose tissue hormone leptin had a negative dynamics under stress conditions, which was an adequate adaptive physiological response to stress. Females with BMD had a significantly high positive dynamics of leptin, while girls with OvBM did not have significant changes in its concentrations, which can be explained by the development of leptin resistance.

scholarly journals Leptin-Activity Modulators and Their Potential Pharmaceutical Applications

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1045
Author(s):  
Marianna Greco ◽  
Marzia De Santo ◽  
Alessandra Comandè ◽  
Emilia Lucia Belsito ◽  
Sebastiano Andò ◽  
...  
Keyword(s):  
Drug Targets ◽  
Leptin Receptor ◽  
Biological Activities ◽  
Reproductive Function ◽  
Leptin Resistance ◽  
Biological Functions ◽  
Leptin Signaling ◽  
Promising Strategy ◽  
Wide Range ◽  
Important Drug

Leptin, a multifunctional hormone primarily, but not exclusively, secreted in adipose tissue, is implicated in a wide range of biological functions that control different processes, such as the regulation of body weight and energy expenditure, reproductive function, immune response, and bone metabolism. In addition, leptin can exert angiogenic and mitogenic actions in peripheral organs. Leptin biological activities are greatly related to its interaction with the leptin receptor. Both leptin excess and leptin deficiency, as well as leptin resistance, are correlated with different human pathologies, such as autoimmune diseases and cancers, making leptin and leptin receptor important drug targets. The development of leptin signaling modulators represents a promising strategy for the treatment of cancers and other leptin-related diseases. In the present manuscript, we provide an update review about leptin-activity modulators, comprising leptin mutants, peptide-based leptin modulators, as well as leptin and leptin receptor specific monoclonal antibodies and nanobodies.

scholarly journals Comparison of Two New Mouse Models of Polygenic Type 2 Diabetes at the Jackson Laboratory, NONcNZO10Lt/J and TALLYHO/JngJ

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Edward H. Leiter ◽  
Marjorie Strobel ◽  
Adam O'Neill ◽  
David Schultz ◽  
Andrew Schile ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Models ◽  
Leptin Receptor ◽  
Reproductive Function ◽  
Leptin Resistance ◽  
Morbidly Obese ◽  
Progressive Development ◽  
New Models ◽  
Juvenile Onset Diabetes

This review compares two novel polygenic mouse models of type 2 diabetes (T2D), TALLYHO/JngJ and NONcNZO10/LtJ, and contrasts both with the well-known C57BLKS/J-Leprdb(db/db) monogenic diabesity model. We posit that the new polygenic models are more representative of the “garden variety” obesity underlying human T2D in terms of their polygenetic rather than monogenic etiology. Moreover, the clinical phenotypes in these new models are less extreme, for example, more moderated development of obesity coupled with less extreme endocrine disturbances. The more progressive development of obesity produces a maturity-onset development of hyperglycemia in contrast to the juvenile-onset diabetes observed in the morbidly obesedb/dbmodel. Unlike the leptin receptor-deficientdb/dbmodels with central leptin resistance, the new models develop a progressive peripheral leptin resistance and are able to maintain reproductive function. Although the T2D pathophysiology in both TALLYHO/JngJ and NONcNZO10/LtJ is remarkably similar, their genetic etiologies are clearly different, underscoring the genetic heterogeneity underlying T2D in humans.

Allometry of the distribution of adipose tissue in Carnivora

1992 ◽  
Vol 70 (2) ◽  
pp. 342-347 ◽  
Author(s):  
Caroline M. Pond ◽  
Malcolm A. Ramsay
Keyword(s):  
Adipose Tissue ◽  
Lean Body Mass ◽  
Body Mass ◽  
Gross Anatomy ◽  
Allometric Equations ◽  
Polar Bears ◽  
Total Body Mass ◽  
Abdominal Adipose Tissue ◽  
Total Body ◽  
The Tropics

The gross masses of intra-abdominal viscera and superficial and intra-abdominal adipose tissue are compared in 41 randomly obtained Carnivora. The mass of the intra-abdominal viscera scales as (lean body mass)0.76. In a sample of 28 Carnivora native to the tropics or the temperate zone, in which dissectible adipose tissue is more than 8.4% of the total body mass, superficial adipose tissue scales isometrically to lean body mass, but intra-abdominal adipose tissue increases as (lean body mass)0.74. Comparable measurements from 13 adult and subadult wild polar bears (Ursus maritimus) fit these allometric equations, indicating that the partitioning of adipose tissue between internal and superficial depots can be fully explained by the fact that these animals are larger and more obese than most other Carnivora. There is no evidence for adaptation of the gross anatomy of the adipose tissue of polar bears to their semi-aquatic habits or arctic habitat.

scholarly journals A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Ingrid Koerber-Rosso ◽  
Stephanie Brandt ◽  
Julia von Schnurbein ◽  
Pamela Fischer-Posovszky ◽  
Josef Hoegel ◽  
...  
Keyword(s):  
Animal Studies ◽  
Weight Status ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Reproductive Function ◽  
Pathogenic Variant ◽  
Human Studies ◽  
Fat Percentage ◽  
Pathogenic Variants

AbstractLeptin (LEP) and leptin receptor (LEPR) play a major role in energy homeostasis, metabolism, and reproductive function. While effects of biallelic likely pathogenic variants (-/-) on the phenotype are well characterized, effects of mono-allelic likely pathogenic variants (wt/-) in the LEP and LEPR gene on the phenotype compared to wild-type homozygosity (wt/wt) have not been systematically investigated. We identified in our systematic review 44 animal studies (15 on Lep, 29 on Lepr) and 39 studies in humans reporting on 130 mono-allelic likely pathogenic variant carriers with 20 distinct LEP variants and 108 heterozygous mono-allelic likely pathogenic variant carriers with 35 distinct LEPR variants. We found indications for a higher weight status in carriers of mono-allelic likely pathogenic variant in the leptin and in the leptin receptor gene compared to wt/wt, in both animal and human studies. In addition, animal studies showed higher body fat percentage in Lep and Lepr wt/- vs wt/wt. Animal studies provided indications for lower leptin levels in Lep wt/- vs. wt/wt and indications for higher leptin levels in Lepr wt/- vs wt/wt. Data on leptin levels in human studies was limited. Evidence for an impaired metabolism in mono-allelic likely pathogenic variants of the leptin and in leptin receptor gene was not conclusive (animal and human studies). Mono-allelic likely pathogenic variants in the leptin and in leptin receptor gene have phenotypic effects disposing to increased body weight and fat accumulation.

scholarly journals The Phlorotannin-Rich Fraction of Ecklonia cava Extract Attenuated the Expressions of the Markers Related with Inflammation and Leptin Resistance in Adipose Tissue

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Junwon Choi ◽  
Ji Tae Jang ◽  
Chang Hu Choi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
T Cell ◽  
Chronic Inflammation ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Ecklonia Cava ◽  
M2 Macrophage ◽  
Socs3 Expression ◽  
Treatment Of Obesity ◽  
Central Leptin Resistance

Obesity is associated with systemic chronic inflammation, and it induces central leptin resistance which blocks the appetite-suppressing effect of leptin and leptin resistance in adipocytes. In the present study, we evaluated the effects of Ecklonia cava extract (ECE), which contained rich phlorotannins, on inflammation and leptin resistance in the adipose tissue of a diet-induced obese model. Effects of ECE on fat deposition, inflammation, M1/M2 macrophage, and T-cell infiltrations were investigated, and leptin resistance and SOCS3 were also measured in adipose tissue. Furthermore, ECE attenuated the expression of inflammation-related receptors such as TLR4 and RAGE and leptin resistance by reducing SOCS3 expression, increasing expression of leptin receptor in adipose tissue, and increasing lipolysis. ECE showed antiadiposity and anti-inflammatory effects, attenuated leptin resistance, and increased lipolysis in the diet-induced obese model. This study shows that ECE is a suitable dietary supplement candidate for the prevention or treatment of obesity or obesity-associated diseases, especially inflammation-related diseases.

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