Signaling Role of Adipocyte Leptin in Prostate Cell Proliferation Induced by Trichomonas vaginalis

Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.

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Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression

Journal of Endocrinology ◽

10.1677/joe.0.1810297 ◽

2004 ◽

Vol 181 (2) ◽

pp. 297-306 ◽

Cited By ~ 69

Author(s):

J Wilsey ◽

PJ Scarpace

Keyword(s):

Caloric Restriction ◽

Leptin Receptor ◽

Fold Increase ◽

Receptor Expression ◽

Male Rats ◽

Receptor Protein ◽

Leptin Signaling ◽

Stat3 Phosphorylation ◽

Long Form

The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in diet-induced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344xBN male rats, aged 6 months, were given an i.c.v. injection containing 2 micro g leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin induced a >6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptin-stimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptin-resistant DIO animals.

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Long-term consequences of the absence of leptin signaling in early life

eLife ◽

10.7554/elife.40970 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 11

Author(s):

Angela M Ramos-Lobo ◽

Pryscila DS Teixeira ◽

Isadora C Furigo ◽

Helen M Melo ◽

Natalia de M Lyra e Silva ◽

...

Keyword(s):

Early Life ◽

Arcuate Nucleus ◽

Leptin Receptor ◽

Brain Growth ◽

Leptin Signaling ◽

Developmental Problems ◽

The Poor ◽

Long Term Consequences

Leptin regulates energy balance and also exhibits neurotrophic effects during critical developmental periods. However, the actual role of leptin during development is not yet fully understood. To uncover the importance of leptin in early life, the present study restored leptin signaling either at the fourth or tenth week of age in mice formerly null for the leptin receptor (LepR) gene. We found that some defects previously considered irreversible due to neonatal deficiency of leptin signaling, including the poor development of arcuate nucleus neural projections, were recovered by LepR reactivation in adulthood. However, LepR deficiency in early life led to irreversible obesity via suppression of energy expenditure. LepR reactivation in adulthood also led to persistent reduction in hypothalamic Pomc, Cartpt and Prlh mRNA expression and to defects in the reproductive system and brain growth. Our findings revealed that early defects in leptin signaling cause permanent metabolic, neuroendocrine and developmental problems.

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Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth

Nature Communications ◽

10.1038/s41467-019-12308-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 19

Author(s):

Øyvind Helgeland ◽

Marc Vaudel ◽

Petur B. Juliusson ◽

Oddgeir Lingaas Holmen ◽

Julius Juodakis ◽

...

Keyword(s):

Leptin Receptor ◽

Genome Wide Association Study ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Transient Effect ◽

Childhood Growth ◽

Leptin Signaling ◽

Genome Wide

Abstract Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6–12 months (rs2767486, P6m = 2.0 × 10−21, β6m = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y = 1.3 × 10−8, β1.5y = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.

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Abstract P178: The Role of Lateral Hypothalamic Leptin Signaling in Metabolic and Cardiovascular Regulation

Hypertension ◽

10.1161/hyp.70.suppl_1.p178 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Huxing Cui ◽

Eva Rodriguez Cruz

Keyword(s):

Leptin Receptor ◽

Nervous Activity ◽

Cardiovascular Regulation ◽

Brain Regions ◽

Sympathetic Nervous Activity ◽

Hypothalamic Area ◽

Leptin Signaling ◽

Lateral Hypothalamic ◽

Sympathetic Regulation

While neurons in the lateral hypothalamic area (LHA) are clearly involved in feeding, metabolism, and cardiovascular regulation, neurochemically and neuroanatomically heterogeneous nature of LHA neurons has been a challenge in understanding their function in physiological regulation. We have recently identified a unique subset of LHA GABAergic neurons, which are distinct from well-known orexin and MCH neurons, that co-express two metabolically important leptin receptor (LepR) and melanocortin-4 receptor (MC4R), suggesting that these neurons might be the important targets of leptin and melanocortin for metabolic and cardiovascular regulation. Here we show that LHA LepR-positive neurons innervate broadly to intra- and extra-hypothalamic brain regions important for feeding, sympathetic nervous activity, and cardiovascular function, including but not limited to arcuate nucleus, paraventricular nucleus of hypothalamus, parabrachial nucleus, and nucleus of the solitary tract. Stereotaxic microinfusion of leptin into the LHA increases renal sympathetic nerve activity (RSNA) (% changes from baseline at 4 th hour: vehicle -25.03 ± 7.09 % vs leptin 100.23 ± 26.94 %, p<0.001); and specific deletion of LepR from LHA significantly increase body weight when fed high-fat diet (44.5 ± 1.9g vs 52.5 ± 2.5g, p<0.01); and selective chemogenetic activation of LHA LepR+ neurons decrease feeding and increase physical activity. Our findings identify the LHA as a novel brain site for leptin to integrate feeding, metabolism and sympathetic regulation. Further investigation of the role of LHA leptin signaling in blood pressure regulation is underway.

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Leptin-deficient (Ob/Ob) mice are resistant to experimental colitis: Role of pro-inflammatory cytokines

Gastroenterology ◽

10.1016/s0016-5085(01)80599-0 ◽

2001 ◽

Vol 120 (5) ◽

pp. A122-A122

Author(s):

B SIEGMUND ◽

F GAMBONIROBERTSON ◽

G FANTUZZI

Keyword(s):

Inflammatory Cytokines ◽

Experimental Colitis ◽

Pro Inflammatory Cytokines

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The role of inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy as a result of ART

HEALTH OF WOMAN ◽

10.15574/hw.2016.111.73 ◽

2016 ◽

pp. 73-76

Author(s):

B.M. Ventskivskiy ◽

◽

I.V. Poladych ◽

S.O. Avramenko ◽

◽

...

Keyword(s):

Assisted Reproductive Technology ◽

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Local Level ◽

Multiple Pregnancy ◽

Reproductive Technology ◽

System Level ◽

Premature Labor ◽

Pro Inflammatory Cytokines

In recent years there has been an increase in the frequency of multiple pregnancies and the associated perinatal losses. It is a result of multiple pregnancy in ART refers to a high-risk gestation, at which premature births occur in 2 times more often than in singleton pregnancies. The objective: to determine the role of pro-inflammatory cytokines in the pathogenesis of premature labor in multiple pregnancy, as a result of assisted reproductive technology. Patients and methods. to determine the pro-inflammatory cytokines that all pregnant with bagtopliddyam held immunosorbent assay, defined concentrations of interleukin (IL) in serum and cervical mucus. Results. The analysis of the levels of pro-inflammatory cytokines (IL-1, IL-8) in the test environment, found high concentrations in the surveyed women with multiple pregnancy, due to the use of ART, compared with spontaneous multiple and singleton pregnancy. Increased concentration of proinflammatory cytokines in patients with multiple pregnancy by ART is associated with their synthesis at the system level, it stimulated foci of inflammation in the female genitals and extragenital localization. This correlates with the clinical data and statistical analysis, patients with multiple pregnancy as a result of ART had weighed infectious-inflammatory history. Conclusion. The study showed that elevated levels of proinflammatory cytokines in the systemic and local level in patients with multiple pregnancy due to ART, typical for women with miscarriage, because of the physiological course of pregnancy characterized by the predominance of anti-inflammatory cytokines that prevent rejection of the fetus as a foreign factor. Based on the data obtained proved the role of systemic inflammatory factors in the genesis of preterm labor in women with a multiple pregnancy, as a result of assisted reproductive technology. Key words: multiple pregnancy, assisted reproductive technology, premature birth, interleukine-1, interleukine-8.

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Role of Oxidative Stress, Pro-Inflammatory Cytokines, Leptin and Adiponectin in Organophosphorus-Induced Insulin Resistance in Wistar Albino Rats

Asian journal of biochemical and pharmaceutical research ◽

10.24214/ajbpr/8/2/5866 ◽

2018 ◽

Vol 8 (2) ◽

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Inflammatory Cytokines ◽

Albino Rats ◽

Wistar Albino Rats ◽

Pro Inflammatory Cytokines

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Use of riboflavinum and magnesium citrate in obstetrics and gynecology

GYNECOLOGY ◽

10.26442/20795696.2018.6.000045 ◽

2018 ◽

Vol 20 (6) ◽

pp. 60-66

Author(s):

O A Gromova ◽

I Yu Torshin ◽

N K Tetruashvili

Keyword(s):

Thrombus Formation ◽

Sirtuin 1 ◽

Obstetrics And Gynecology ◽

Inflammatory Factor ◽

Vitamin B2 ◽

Magnesium Citrate ◽

Fetal Malformations ◽

Folate Cycle ◽

Pro Inflammatory Cytokines

Low provision of cells with vitamin B2 and magnesium leads to a decrease in the activity of the sirtuin-1 deacetylase and an increase in the activity of the pro-inflammatory factor NF-kB, a decrease in the levels of glutathione, an increase in the levels of homocysteine, thrombus formation, the activity of mitochondria, the development of migraine, convulsions and miscarriage. The role of riboflavin in the regulation of the folate cycle in the genotype MTHFR 677TT for the prevention of folatresistant fetal malformations, the advantages of an aqueous solution of riboflavin and magnesium citrate is considered. The data on titanium dioxide, which increases the level of pro-inflammatory cytokines IL-1b, IL-4, IL-5, IL-6, G-CSF, CCL-2, CCL-3, CCL-4, are presented.

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Understanding the role of Inflammasome in Angina Pectoris

Current Protein and Peptide Science ◽

10.2174/1389203721999201208200242 ◽

2020 ◽

Vol 21 ◽

Author(s):

Ishita Sharma ◽

Tapan Behl ◽

Simona Bungau ◽

Monika Sachdeva ◽

Arun Kumar ◽

...

Keyword(s):

Coronary Artery ◽

Angina Pectoris ◽

Nlrp3 Inflammasome ◽

Vital Role ◽

Death Process ◽

Cell Death Process ◽

Artery Disease ◽

Species Production ◽

Pro Inflammatory Cytokines

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

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