scholarly journals Expression of Leptin Receptor in Human Endometrium and Fluctuation during the Menstrual Cycle

2000 ◽  
Vol 85 (5) ◽  
pp. 1946-1950 ◽  
Author(s):  
Jo Kitawaki ◽  
Hisato Koshiba ◽  
Hiroaki Ishihara ◽  
Izumi Kusuki ◽  
Katsumi Tsukamoto ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Splice Variants ◽  
Human Endometrium ◽  
Messenger Ribonucleic Acid ◽  
Leptin Receptors ◽  
Decidual Tissue ◽  
Long Form ◽  
Uterine Diseases ◽  
Disease Free

Abstract Leptin is secreted by adipocytes and regulates appetite through interaction with hypothalamic leptin receptors (OB-R). Accumulated evidence shows that leptin is involved in the stimulation of reproductive functions and that local expression of leptin and OB-R in the ovary, oocyte, embryo, and placenta plays a role in early development. To investigate the role of leptin in implantation, we examined the expression of OB-R and leptin in the human endometrium. Northern and Western blot analyses and RT-PCR showed that the long form of OB-R (OB-RL) messenger ribonucleic acid (mRNA) and protein were expressed. In contrast, leptin mRNA or protein was not detected. All of the splice variants of OB-R (OB-RT) and OB-RL transcripts were expressed in 90% and 84% of the cases, respectively. OB-R mRNA expression peaked in the early secretory phase. Decidual tissue of early gestation also expressed OB-RT and OB-RL. Their incidence and abundance were comparable among endometria with benign uterine diseases and disease-free endometria and were not related to a body mass index within the normal range. The present results indicate that OB-R, but not leptin, is expressed in the human endometrium.

Hyperleptinemia and reduced TNF-α secretion cause resistance of db/db mice to endotoxin

2003 ◽  
Vol 284 (3) ◽  
pp. R763-R770 ◽  
Author(s):  
Abram M. Madiehe ◽  
Tiffany D. Mitchell ◽  
Ruth B. S. Harris
Keyword(s):  
Rectal Temperature ◽  
Leptin Receptor ◽  
Short Form ◽  
Endotoxic Shock ◽  
Cytokine Receptors ◽  
Leptin Receptors ◽  
Leptin Deficiency ◽  
Tnf Α ◽  
Long Form

Leptin deficiency in ob/ob mice increases susceptibility to endotoxic shock, whereas leptin pretreatment protects them against LPS-induced lethality. Lack of the long-form leptin receptor (Ob-Rb) in db/db mice causes resistance. We tested the effects of LPS in C57BL/6J db3J/db3J (BL/3J) mice, which express only the circulating leptin receptors, compared with C57BL/6J db/db (BL/6J) mice, which express all short-form and circulating isoforms of the leptin receptor. Intraperitoneal injections of LPS significantly decreased rectal temperature and increased leptin, corticosterone, and free TNF-α in fed and fasted BL/3J and BL/6J mice. TNF-α was increased three- and fourfold in BL/3J and BL/6J, respectively. LPS (100 μg) caused 50% mortality of fasted BL/6J mice but caused no mortality in fasted BL/3J mice. Pretreatment of fasted BL/3J mice with 30 μg leptin prevented the drop in rectal temperature, blunted the increase in corticosterone, but had no effect on TNF-α induced by 100 μg LPS. Taken together, these data provide evidence that fasted BL/3J mice are more resistant than BL/6J mice to LPS toxicity, presumably due to the absence of leptin receptors in BL/3J mice. This resistance may be due to high levels of free leptin cross-reacting with other cytokine receptors.

scholarly journals 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

2004 ◽  
Vol 181 (2) ◽  
pp. 297-306 ◽  
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.

scholarly journals Suppression of Leptin Receptor Messenger Ribonucleic Acid and Leptin Responsiveness in the Ventromedial Nucleus of the Hypothalamus during Pregnancy in the Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3868-3874 ◽  
Author(s):  
S. R. Ladyman ◽  
D. R. Grattan
Keyword(s):  
Choroid Plexus ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Ventromedial Nucleus ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Messenger Ribonucleic Acid ◽  
Leptin Receptors ◽  
Receptor Isoforms

Abstract Pregnancy in the rat is a state of leptin resistance associated with impaired leptin signal transduction in the hypothalamus. The aim of this study was to determine whether this leptin-resistant state is mediated by a change in the level of leptin receptors in the hypothalamus. Real-time RT-PCR was used to determine levels of mRNA for the various leptin receptor isoforms in a number of microdissected hypothalamic nuclei and the choroid plexus. To investigate the functional activation of the leptin receptor, immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3) was examined in the arcuate nucleus and the ventromedial nucleus of the hypothalamus (VMH) of fasted diestrous and d-14 pregnant rats after an intracerebroventricular (i.c.v.) injection of either leptin (4 μg) or vehicle. A significant reduction of Ob-Rb mRNA levels was observed in the VMH during pregnancy compared with the nonpregnant controls. Furthermore, in pregnant rats the number of cells positive for leptin-induced pSTAT3 in the VMH was greatly reduced during pregnancy compared with nonpregnant rats. There were no differences in the level of Ob-Rb mRNA or in the number of leptin-induced pSTAT3-positive cells in the arcuate nucleus of nonpregnant and pregnant rats. These data implicate the VMH as a key hypothalamic site involved in pregnancy-induced leptin resistance. There were also reduced levels of mRNA for Ob-Ra, a proposed leptin transporter molecule, in the choroid plexus on d 7 and 21 of pregnancy. Hence, diminished transport of leptin into the brain may also contribute to pregnancy-induced leptin resistance.

scholarly journals Role of leptin receptors in granulosa cells during ovulation

Reproduction ◽  
2014 ◽  
Vol 147 (2) ◽  
pp. 221-229 ◽  
Author(s):  
Lisa Dupuis ◽  
Yasmin Schuermann ◽  
Tamara Cohen ◽  
Dayananda Siddappa ◽  
Anitha Kalaiselvanraja ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Leptin Receptor ◽  
Critical Role ◽  
Follicular Development ◽  
Reproductive Function ◽  
Control Treatment ◽  
Maturation Stage ◽  
Leptin Receptors ◽  
Enhancer Binding Protein

Leptin is an important hormone influencing reproductive function. However, the mechanisms underpinning the role of leptin in the regulation of reproduction remain to be completely deciphered. In this study, our objective is to understand the mechanisms regulating the expression of leptin receptor (Lepr) and its role in ovarian granulosa cells during ovulation. First, granulosa cells were collected from superovulated mice to profile mRNA expression of Lepr isoforms (LeprA and LeprB) throughout follicular development. Expression of LeprA and LeprB was dramatically induced in the granulosa cells of ovulating follicles at 4 h after human chorionic gonadotropin (hCG) treatment. Relative abundance of both mRNA and protein of CCAAT/enhancer-binding protein β (Cebpβ) increased in granulosa cells from 1 to 7 h post-hCG. Furthermore, chromatin immunoprecipitation assay confirmed the recruitment of Cebpβ to Lepr promoter. Thus, hCG-induced transcription of Lepr appears to be regulated by Cebpβ, which led us to hypothesise that Lepr may play a role during ovulation. To test this hypothesis, we used a recently developed pegylated superactive mouse leptin antagonist (PEG-SMLA) to inhibit Lepr signalling during ovulation. I.p. administration of PEG-SMLA (10 μg/g) to superovulated mice reduced ovulation rate by 65% compared with control treatment. Although the maturation stage of the ovulated oocytes remained unaltered, ovulation genes Ptgs2 and Has2 were downregulated in PEG-SMLA-treated mice compared with control mice. These results demonstrate that Lepr is dramatically induced in the granulosa cells of ovulating follicles and this induction of Lepr expression requires the transcription factor Cebpβ. Lepr plays a critical role in the process of ovulation by regulating, at least in part, the expression of the important genes involved in the preovulatory maturation of follicles.

scholarly journals Expression of leptin and leptin receptors in colorectal cancer—an immunohistochemical study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7624 ◽  
Author(s):  
Saad M. Al-Shibli ◽  
Norra Harun ◽  
Abdelkader E. Ashour ◽  
Mohd Hanif B. Mohd Kasmuri ◽  
Shaikh Mizan
Keyword(s):  
Colorectal Cancer ◽  
Leptin Receptor ◽  
Immunohistochemical Study ◽  
Lymph Node Involvement ◽  
Colon Tissue ◽  
Leptin Receptors ◽  
Malaysian Population ◽  
Node Involvement ◽  
Cancer Tissues

Obesity is demonstrated to be a risk factor in the development of cancers of various organs, such as colon, prostate, pancreas and so on. Leptine (LEP) is the most renowned of the adipokines. As a hormone, it mediates its effect through leptin receptor (LEPR), which is widely expressed in various tissues including colon mucosa. In this study, we have investigated the degree of expression of LEP and LEPR in colorectal cancer (CRC). We collected 44 surgically resected colon cancer tissues along with normal adjacent colon tissue (NACT) from a sample of CRC patients from the Malaysian population and looked for leptin and leptin receptors using immunohistochemistry (IHC). All the samples showed low presence of both LEP and LEPR in NACT, while both LEP and LEPR were present at high intensity in the cancerous tissues with 100% and 97.7% prevalence, respectively. Both were sparsed in the cytoplasm and were concentrated beneath the cell membrane. However, we did not find any significant correlation between their expression and pathological parameters like grade, tumor size, and lymph node involvement. Our study further emphasizes the possible causal role of LEP and LEPR with CRC, and also the prospect of using LEPR as a possible therapeutic target.

Cellular, molecular and physiological aspects of leptin: Potential application in animal production

1998 ◽  
Vol 78 (4) ◽  
pp. 463-472 ◽  
Author(s):  
Kim L. Hossner
Keyword(s):  
Leptin Receptor ◽  
Short Form ◽  
Signal Transduction Pathway ◽  
Leptin Receptors ◽  
Specific Effects ◽  
Key Words Leptin ◽  
Fat Stores ◽  
Regulate Food Intake ◽  
Specific Receptors

This review encompasses the biochemistry and physiology of the newly discovered adipose hormone, leptin. Leptin appears to fulfill the role of the long sought after "lipostat", which functions to regulate energy intake in relation to body stores in the form of fat. Leptin is a 16 000 Dalton polypeptide which interacts with specific receptors in the hypothalamus to regulate food intake and body fat stores. Leptin receptors exist in several forms, which can be divided into those with small cytoplasmic domains and one with a single long cytoplasmic tail. The latter is thought to mediate most of leptin's effects, acting through the JAK-STAT signal transduction pathway. Several reports have shown direct effects of leptin on tissues with the short form of the leptin receptor. Specific effects of leptin on appetite, energy metabolism and reproduction are reviewed. Leptin may prove to be most useful to animal producers as a stimulant of the reproductive system or as a molecular marker to genetically select livestock for improved reproductive capacities or carcass characteristics, while leptin antagonists may improve metabolic rate and body composition. Key words: Leptin, obese protein, leptin receptor, review, livestock production

scholarly journals Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation

2014 ◽  
Vol 307 (3) ◽  
pp. E316-E325 ◽  
Author(s):  
Michael E. Hall ◽  
Matthew W. Maready ◽  
John E. Hall ◽  
David E. Stec
Keyword(s):  
Body Weight ◽  
Lipid Accumulation ◽  
Leptin Receptor ◽  
Systolic Function ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Cardiac Lipid ◽  
Leptin Receptors ◽  
Triglyceride Accumulation ◽  
Long Form

Increased leptin levels have been suggested to contribute to cardiac hypertrophy and attenuate cardiac lipid accumulation in obesity, although it has been difficult to separate leptin's direct effects from those caused by changes in body weight and adiposity. To determine whether leptin attenuates cardiac lipid accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we generated a novel mouse model in which the long form of the leptin receptor (LepR) was “rescued” only in cardiomyocytes of obese db/db mice. Reexpression of cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced cardiac triglycerides and improved cardiac function. Compared with lean wild-type (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5 ± 0.07 in db/db vs. 1.9 ± 0.08 and 1.8 ± 0.11 in WT and db/db-cardiac LepR rescue mice, respectively. No differences in systolic function were observed. Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides were significantly higher in db/db compared with WT and db/db cardiac LepR rescue mice, averaging 13.4 ± 4.2 vs. 3.8 ± 1.6 vs. 3.8 ± 0.7 mg/g, respectively. These results demonstrate that despite significant obesity and increases in plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected against myocardial lipid accumulation. However, we found no evidence that leptin directly causes LVH.

scholarly journals The role of leptin in selected skin diseases

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Klaudia Dopytalska ◽  
Agnieszka Baranowska-Bik ◽  
Marek Roszkiewicz ◽  
Wojciech Bik ◽  
Irena Walecka
Keyword(s):  
Lupus Erythematosus ◽  
Intracellular Signaling ◽  
Leptin Receptor ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Wide Distribution ◽  
Signal Transducers ◽  
Leptin Receptors ◽  
Pleiotropic Functions

Abstract Leptin is an adipokine, adipocyte-derived compound, which acts both as a hormone and cytokine. It is mainly synthesized by adipocytes of white adipose tissue. Leptin possesses pleiotropic functions including, among others, stimulation of angiogenesis and production of proinflammatory cytokines. The various types of leptin activity are related to the wide distribution of leptin receptors. This adipokine acts by activating intracellular signaling cascades such as JAKs (Janus kinases), STATs (signal transducers and activators of transcription), and others. In a course of obesity, an increased serum level of leptin coexists with tissue receptor resistance. It has been reported that enhanced leptin levels, leptin receptor impairment, and dysfunction of leptin signaling can influence skin and hair. The previous studies revealed the role of leptin in wound healing, hair cycle, and pathogenesis of skin diseases like psoriasis, lupus erythematosus, and skin cancers. However, the exact mechanism of leptin’s impact on the skin is still under investigation. Herein, we present the current knowledge concerning the role of leptin in psoriasis and selected skin diseases.

Sign in / Sign up

Export Citation Format

Share Document