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

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 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.

Leptin action is modified by an interaction between dietary fat content and ambient temperature

2004 ◽  
Vol 287 (5) ◽  
pp. R1250-R1255 ◽  
Author(s):  
Andrea L. Haltiner ◽  
Tiffany D. Mitchell ◽  
Ruth B. S. Harris
Keyword(s):  
Energy Intake ◽  
Body Fat ◽  
Dietary Fat ◽  
Leptin Receptor ◽  
Environmental Temperature ◽  
Short Form ◽  
Uncoupling Protein ◽  
Fat Content ◽  
High Fat ◽  
Leptin Receptors

Mice adapted to a high-fat diet are reported to be leptin resistant; however, we previously reported that mice fed a high-fat (HF) diet and housed at 23°C remained sensitive to peripheral leptin and specifically lost body fat. This study tested whether leptin action was impaired by a combination of elevated environmental temperature and a HF diet. Male C57BL/6 mice were adapted to low-fat (LF) or HF diet from 10 days of age and were housed at 27°C from 28 days of age. From 35 days of age, baseline food intake and body weight were recorded for 1 wk and then mice on each diet were infused with 10 μg leptin/day or PBS from an intraperitoneal miniosmotic pump for 13 days. HF-fed mice had a higher energy intake than LF-fed mice and were heavier but not fatter. Serum leptin was lower in PBS-infused HF- than LF-fed mice. Leptin significantly inhibited energy intake of both LF-fed and HF-fed mice, and this was associated with a significant increase in hypothalamic long-form leptin receptors with no change in short-form leptin receptor or brown fat uncoupling protein-1 mRNA expression. Leptin significantly inhibited weight gain in both LF- and HF-fed mice but reduced the percentage of body fat mass only in LF-fed mice. The percentage of lean and fat tissue in HF-fed mice did not change, implying that overall growth had been inhibited. These results suggest that dietary fat modifies the mechanisms responsible for leptin-induced changes in body fat content and that those in HF-fed mice are sensitive to environmental temperature.

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.

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.

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.

scholarly journals A possible role of neuropeptide Y, agouti-related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat

Diabetologia ◽  
2004 ◽  
Vol 48 (1) ◽  
pp. 140-148 ◽  
Author(s):  
M. L�pez ◽  
L. M. Seoane ◽  
S. Tovar ◽  
M. C. Garc�a ◽  
R. Nogueiras ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Related Protein ◽  
Receptor Isoforms ◽  
Agouti Related Protein

scholarly journals Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 18
Author(s):  
Laura Toma ◽  
Camelia Sorina Stancu ◽  
Anca Volumnia Sima
Keyword(s):  
Plasma Proteins ◽  
Diabetes Complications ◽  
Vascular Complications ◽  
High Density Lipoproteins ◽  
Diabetic Patients ◽  
Inflammatory Stress ◽  
Glycation End Products ◽  
Molecular Therapies ◽  
Specific Receptors

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.

scholarly journals The LEPR Gene Is Associated with Reproductive Seasonality Traits in Rasa Aragonesa Sheep

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2448
Author(s):  
Kenza Lakhssassi ◽  
Malena Serrano ◽  
Belén Lahoz ◽  
María Pilar Sarto ◽  
Laura Pilar Iguácel ◽  
...  
Keyword(s):  
Amino Acid Change ◽  
Leptin Receptor ◽  
Extreme Values ◽  
Reproductive Traits ◽  
Reproductive Seasonality ◽  
Synonymous Substitutions ◽  
Lepr Gene ◽  
Exon 20 ◽  
First Time

The aim of this study was to characterize and identify causative polymorphisms in the leptin receptor (LEPR) gene responsible for the seasonal variation of reproductive traits in sheep. Three reproductive seasonality traits were studied: the total days of anoestrous (TDA), the progesterone cycling months (P4CM) and the oestrous cycling months (OCM). In total, 18 SNPs were detected in 33 ewes with extreme values for TDA and OCM. Six SNPs were non-synonymous substitutions and two of them were predicted in silico as deleterious: rs596133197 and rs403578195. These polymorphisms were then validated in 239 ewes. The SNP rs403578195, located in exon 8 and leading to a change of alanine to glycine (Ala284Gly) in the extracellular domain of the protein, was associated with the OCM trait, being the G allele associated with a decrease of 12 percent of the OCM trait. Haplotype analyses also suggested the involvement of other non-synonymous SNP located in exon 20 (rs405459906). This SNP also produces an amino acid change (Lys1069Glu) in the intracellular domain of the protein and segregates independently of rs403578195. These results confirm for the first time the role of the LEPR gene in sheep reproductive seasonality.

scholarly journals Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas
Keyword(s):  
Action Potentials ◽  
Channel Blocker ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Afferent Neurons ◽  
Sodium Channel Blocker ◽  
Voltage Gated Sodium Channels ◽  
New Strategy ◽  
Specific Receptors

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

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