Recombinant Human Leptin protein (LEP)

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Description

Production and Biochemical Properties

Recombinant LEP is produced via heterologous expression systems, optimized for yield and bioactivity:

Production Systems

SystemAdvantagesSource
E. coliHigh yield, low cost, soluble expression
Mammalian (HEK 293)Proper post-translational modifications

Mechanisms of Action

Recombinant LEP mimics endogenous leptin’s signaling via LepR, activating pathways critical for energy balance:

Signaling Pathways

  1. JAK-STAT Pathway:

    • LepR binds leptin → JAK2 autophosphorylation → STAT3 phosphorylation → nuclear translocation → transcriptional regulation .

  2. PI3K and MAPK/ERK Pathways:

    • Modulates insulin sensitivity and anorexigenic effects .

Negative Regulation

RegulatorMechanismSource
SOCS3Inhibits JAK2 phosphorylation
PTP1BDephosphorylates JAK2, reducing signaling

Hypothalamic Effects

  • Inhibits NPY/AgRP neurons and activates POMC neurons, reducing food intake .

  • Rapidly alters synaptic density on hypothalamic neurons (observed within 6 hours) .

Therapeutic Applications and Research Findings

Recombinant LEP has shown promise in obesity and metabolic disorders:

Preclinical Studies

ModelOutcomeSource
Mice (ip injection)Reduced food intake, body weight, serum insulin
BaF3 Leptin R+ CellsDose-dependent proliferation (ED₅₀: 0.4–2 ng/mL)

Clinical Trials

Trial DesignResultsSource
Dose-Escalation (4–24 weeks)Weight loss: -1.9 kg (4 weeks) to -7.1 kg (24 weeks)
Fat Mass Reduction>95% of weight loss in high-dose cohorts
Adverse EffectsMild injection-site reactions

Table 2: Bioactivity Assays

AssayResultSource
BaF3 Cell ProliferationED₅₀: 0.4–2 ng/mL
ELISA BindingLinear range: 1.22–261.45 ng/mL
SDS-PAGESingle band at 13–16 kDa (reducing conditions)

Product Specs

Buffer
0.2 µm filtered 50 mM Phosphate Buffered Saline (PBS), pH 3.5, with 0.02% Tween-20, lyophilized
Form
Liquid or Lyophilized powder
Lead Time
Generally, we can ship products within 1-3 working days of receiving your order. Delivery times may vary depending on the purchasing method or location. Please contact your local distributors for specific delivery times.
Note: All of our proteins are shipped with standard blue ice packs. If you require dry ice shipping, please communicate with us in advance as additional fees may apply.
Shelf Life
The shelf life of our products is dependent on factors such as storage conditions, buffer ingredients, temperature, and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Storage Condition
Upon receipt, store at -20°C/-80°C. Aliquoting is recommended for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag-Free
Synonyms
FLJ94114; LEP; LEP_HUMAN; LEPD; Leptin (murine obesity homolog); Leptin (obesity homolog, mouse); Leptin; Leptin Murine Obesity Homolog; Leptin Precursor Obesity Factor; OB; Obese protein; Obese, mouse, homolog of; Obesity; Obesity factor; Obesity homolog mouse; Obesity Murine Homolog Leptin; OBS; OTTHUMP00000212285
Datasheet & Coa
Please contact us to get it.
Expression Region
22-167aa
Mol. Weight
16.0 kDa
Protein Length
Full Length of Mature Protein
Purity
>97% as determined by SDS-PAGE.
Research Area
Signal Transduction
Source
E.Coli
Species
Homo sapiens (Human)
Target Names
LEP
Uniprot No.

Target Background

Function
Leptin is a crucial regulator of energy balance and body weight control. Once released into the bloodstream, it exerts both central and peripheral effects by binding to the leptin receptor (LEPR) found in various tissues. This binding activates several major signaling pathways.

In the hypothalamus, leptin acts as an appetite-regulating factor. It decreases food intake and increases energy expenditure by inducing anorexigenic factors (suppressing appetite) and suppressing orexigenic neuropeptides (stimulating appetite). Additionally, it regulates bone mass and the secretion of hypothalamo-pituitary-adrenal hormones.

Peripherally, leptin increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, exhibits pro-angiogenic activity on endothelial cells, and modulates both innate and adaptive immunity.

Within the arcuate nucleus of the hypothalamus, leptin activates POMC neurons via depolarization, inducing the expression of FOS and SOCS3, leading to the release of anorexigenic peptides. Conversely, it inhibits NPY neurons via hyperpolarization, inducing SOCS3 expression and reducing the release of orexigenic peptides.

Beyond its well-established satiety-inducing effect, leptin also plays a modulatory role in nutrient absorption. In the intestine, it reduces glucose absorption by enterocytes by activating PKC, which sequentially activates p38, PI3K, and ERK signaling pathways, ultimately inhibiting glucose uptake.

Leptin acts as a growth factor in specific tissues. Through the activation of various signaling pathways, it increases the expression of genes involved in cell cycle regulation, such as CCND1 (via the JAK2-STAT3 pathway), and VEGFA (via the MAPK1/3 and PI3K-AKT1 pathways).

Leptin can also induce apoptosis via the JAK2-STAT3 pathway and upregulation of BIRC5 expression.

As a pro-angiogenic factor, leptin possesses mitogenic activity on vascular endothelial cells and participates in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs).

In innate immunity, leptin modulates the activity and function of neutrophils by enhancing chemotaxis and the secretion of oxygen radicals. It increases phagocytosis by macrophages and promotes the secretion of pro-inflammatory mediators. Additionally, leptin enhances the cytotoxic ability of NK cells.

Leptin plays a pro-inflammatory role, acting synergistically with IL1B to induce NOS2, which promotes the production of IL6, IL8, and Prostaglandin E2 via a signaling pathway involving JAK2, PI3K, MAP2K1/MEK1, and MAPK14/p38.

In adaptive immunity, leptin promotes the differentiation of memory T-cells towards T helper-1 cell immune responses. It increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation through MTOR signaling pathway activation and BCL2 upregulation.
Gene References Into Functions
  1. Elevated levels of chemerin and leptin, coupled with decreased levels of omentin-1 and visfatin, are observed in women with gestational diabetes mellitus complicated by obesity. PMID: 29337272
  2. A recent study elucidated novel molecular events associated with leptin-induced inflammation in ligamentum flavum (LF) tissue. Leptin promotes IL-6 expression, potentially contributing to the understanding of LF fibrosis and hypertrophy. PMID: 29436483
  3. Leptin protein levels were significantly elevated in pre-liver transplantation alcoholics and subsequently decreased post-transplantation. PMID: 29912265
  4. The AA genotype of leptin rs7799039 is associated with metabolic syndrome and higher serum leptin levels in Egyptian women. PMID: 27966294
  5. In critically ill heart failure patients, the circadian rhythm of plasma leptin concentration remains preserved during the first day after admission but is disrupted by the third day. PMID: 29527917
  6. This research suggests a potential link between gastric leptin and microbial-derived metabolites in the context of obesity and diabetes. PMID: 29851973
  7. The results indicate that the LEP rs7799039 allele A is associated with a slight reduction in total and LDL cholesterol, suggesting that this genetic variant may serve as a useful biomarker for cardiometabolic risk in obese patients. PMID: 28975585
  8. This study aimed to determine serum ghrelin and leptin levels in obese and lean Saudi women with Polycystic ovary syndrome and to investigate their relationship to metabolic profiles. PMID: 30131073
  9. The serum leptin level does not exhibit a significant difference between non-obese OSA patients with moderate/severe OSA and those with snoring/mild OSA. PMID: 29174427
  10. Leptin concentrations are consistently higher in the obese group, regardless of their glucose tolerance status. PMID: 29108900
  11. Elevated leptin-to-adiponectin ratio and IL-6 levels were observed in men with prostate cancer. Leptin, chemerin, and IL-6 were associated with Gleason score, and their relationships were interdependent. PMID: 29465157
  12. These findings provide evidence that leptin modulates ovarian cancer cell invasion by stimulating MMP7 expression through the ERK and JNK pathways. PMID: 28885729
  13. This study demonstrates that leptin regulates the pro-inflammatory response in human epidermal keratinocytes. PMID: 29468452
  14. AMH, IGF1, and leptin levels in follicular fluid are not associated with fertility disorders caused by endometriosis or fallopian tube damage. However, they serve as biomarkers for anovulatory fertility disorders. PMID: 29595066
  15. Our data suggest that leptin-mediated OPN upregulation promotes TH2 inflammation in asthma, achieved through the alpha4 integrin and PI3K/AKT signaling pathways. PMID: 29885866
  16. By analyzing a comprehensive dataset of 1129 proteins from 494 obese subjects, this study identified and validated FAM46A as a trans-regulator for leptin. PMID: 29234017
  17. Cord blood klotho levels were inversely correlated with leptin and insulin levels at birth. PMID: 29648999
  18. Estradiol and physical activity were stronger predictors of leptin at menses, while sexual activity was a stronger predictor of leptin at ovulation. These findings suggest that predictors of serum leptin, potentially linked to energy storage and expenditure, vary throughout the menstrual cycle. PMID: 29454804
  19. Leptin, leptin receptor, and apelin receptor genes are associated with susceptibility to coronary artery disease and hypertension. PMID: 29883719
  20. Serum levels of leptin (and adiponectin) were significantly and negatively associated with bone mineral density in patients with knee osteoarthritis. PMID: 29343264
  21. This study provides evidence that polymorphisms in the LEP and LEPR genes are associated with the magnitude of the effects of regular physical activity on glucose and LDL-C levels, respectively. Additionally, we found an association of the G allele of the LEPR polymorphism with body mass and BMI. PMID: 29373433
  22. Increased levels of mucosal leptin may interact with mast cells and the nervous system, contributing to the pathogenesis of diarrhea-predominant irritable bowel syndrome. PMID: 29358881
  23. Data suggest that leptin upregulates the expression of aquaporin-9 in term placenta. These studies utilized placental explants following term birth via cesarean section. PMID: 28942694
  24. By analyzing different estrogen receptor-alpha (ER-α)-positive and ER-α-negative breast cancer cell lines, this research defined the role of CCN5 in the leptin-mediated regulation of growth and invasive capacity. PMID: 29370782
  25. LEP-rs7799039 was significantly associated with an increased risk for excessive gestational weight gain. PMID: 29241578
  26. Higher serum leptin levels can be used as a risk factor for childhood obesity. PMID: 29412799
  27. H. pylori infection decreased serum concentrations of leptin and obestatin in Mexican schoolchildren, suggesting alterations in appetite and energy homeostasis regulation. PMID: 28422951
  28. The data suggest that the stimulatory effects of leptin on the proliferative activity of human normal prostate and prostate cancer cell lines require the expression of leptin receptor variant 1 in the affected cells. PMID: 29115533
  29. The findings suggest that the LEP G2548A genetic polymorphism may increase the susceptibility of cancers in non-Hodgkin's lymphoma (meta-analysis). PMID: 25536622
  30. Features of poor prognosis, such as tumor invasion, lymph node involvement, and distant metastasis, have been documented in several cancer types with higher levels of leptin and/or Ob-R. This review provides a comprehensive overview of the current understanding. Generally, obesity indicates a poorer prognosis in cancer patients. [Review] PMID: 29158066
  31. Clinical data on secondary hyperparathyroidism, primarily derived from patients with chronic kidney disease, suggest a potential inverse association between leptin (LEP) and parathyroid hormone (PTH) in some, but not all, studies. [REVIEW] PMID: 28730419
  32. Data suggest that transient increases in plasma adiponectin levels and transient decreases in plasma leptin levels occur following high-intensity interval exercise in overweight and obese young women. These studies were conducted in Turkey among formerly sedentary women aged 20-30 years. PMID: 28857629
  33. There was no simple, linear association of leptin and physical activity in adults with anorexia nervosa. PMID: 29099750
  34. Neoplastic cells appeared unable to downregulate NOX5 mRNA expression in the presence of leptin. Leptin emerged as a potential activator of ROS production in human epithelial mammary cells, where ROS production was apparently linked to NOX5 activation. This novel finding sheds light on the potential role of obesity-associated hyperleptinemia in mammary cells through the activation of NOX enzymes. PMID: 29048637
  35. Data suggest that serum leptin may be a potential biomarker for predicting sarcopenic obesity and physical performance in knee osteoarthritis. PMID: 28374624
  36. Leptin synergizes with IL-1beta in inducing ELF3 expression in chondrocytes. PMID: 29550824
  37. The nitrogen stable isotopic ratio in hair is positively associated with serum leptin levels. PMID: 29081462
  38. The heterozygous genotype AG of the Single Nucleotide Polymorphism -2548 G/A of the leptin gene (LEP) may reduce the risk of endometrial cancer independently of an individual's overall adiposity. The A allele alone of this polymorphism may be a risk factor for this malignancy in obese women, while the G allele may decrease the hazard in these patients. PMID: 28964972
  39. Pregnant adolescents with leptin concentrations exceeding 20 ng/mL exhibited greater gestational weight gain. Leptin concentration correlated with the length and weight of the newborn. PMID: 28953229
  40. LEP and LEPR single-nucleotide polymorphisms are not associated with genetic susceptibility to systemic lupus erythematosus. PMID: 28244652
  41. The upregulation of miR27 inhibits the pathogenesis of osteoarthritis by targeting leptin and inhibiting the NF-kappaB signaling pathway. PMID: 28627582
  42. There was a direct association between polymorphisms in LEP rs7799039 and ADIPOQ rs1501299 with overweight/obesity, and these genotypes affected the response to breast cancer chemotherapeutic treatment in Mexican women. PMID: 28416193
  43. Habitual intake of SFA, MUFA, and n-3 fatty acids was associated with leptin gene expression in visceral and subcutaneous adipose tissues, suggesting a significant role of both the quality and quantity of fatty acid intake in adipose tissue for regulating leptin expression. PMID: 29031395
  44. The studies established a potential link between leptin and adipocyte insulin responsiveness in an NOS2-dependent manner. PMID: 28739528
  45. Leptin serum levels decrease following bariatric surgery and are predictive of disease remission in type 2 diabetes mellitus patients. PMID: 28734574
  46. This research identified alterations in leptin and SCD-1 in patients with homocystinuria. PMID: 28801090
  47. This study suggests that leptin may play a role in androgenetic alopecia in men. PMID: 28423238
  48. This study is the first to describe the mechanism of leptin-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. PMID: 27345723
  49. The study suggested that leptin accelerated the epithelial mesenchymal transition of A549 cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. PMID: 29524411
  50. This research investigated adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) single nucleotide polymorphisms and their association in obesity. Results showed that ADIPOQ 4522CPMID: 28195351

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Database Links

HGNC: 6553

OMIM: 164160

KEGG: hsa:3952

STRING: 9606.ENSP00000312652

UniGene: Hs.194236

Involvement In Disease
Leptin deficiency (LEPD)
Protein Families
Leptin family
Subcellular Location
Secreted.
Tissue Specificity
Adipose tissue is the main source of leptin. It is also produced by other peripheral tissues such as the skeletal muscle. Expressed by intercalated and striated tracts of submandibular and parotid salivary gland intralobular ducts. Detected by fundic epit

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