研究發(fā)現(xiàn)，LEP通過與大腦中的特定受體結(jié)合，可以調(diào)節(jié)食欲和代謝。最新的研究還發(fā)現(xiàn)，LEP可能還參與了腫瘤的發(fā)生和發(fā)展過程。一些研究表明，LEP可以通過多種機制抑制腫瘤生長，具有一定的抗腫瘤作用。這些研究為進一步研究LEP在腫瘤治療中的應(yīng)用提供了新思路和方向。

Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity. In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides. In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption. Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways. May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells (Probable). Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38. In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses. Increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.

1. Leptin was found to stimulate mast cells to degranulation and histamine release. It induced the intracellular Ca(2+) increase, as well. In response to leptin stimulation, mast cells generated and released cysLTs and chemokine CCL3. Leptin-induced upregulation of CYSLTR1 and CYSLTR2 surface expression was observed. It stimulated mast cells to migratory response, even in the absence of extracellular matrix (ECM) proteins. PMID: 30019195
2. Leptin and chemerin levels: DJOS lowered leptin and chemerin plasma levels versus SHAM, while HF/HF, CD/HF, and HF/CD significantly increased leptin and chemerin plasma levels when compared to CD/CD. PMID: 29849871
3. These results suggest that leptin and its receptor may serve significant roles in the pathogenesis of varicocele-induced testicular dysfunction. PMID: 29568885
4. The role of brain-derived serotonin and peripheral leptin in the regulation of bone metabolism and strength in young rats, was examined. PMID: 28797891
5. Study have generated Lep- mutant rat model to study obesity related diseases. I14 in LEP is essential for LEP-LEPR interaction and biological function, and LepDeltaI14/DeltaI14 rats recapitulate the expected mutant phenotypes of LEP null animals. Structural study of LEPDeltaI14-LEPR interaction reveal the defective ligand/receptor interaction due to deletion of this 14th Ile in mature LEP. PMID: 27378381
6. The upregulation of miR27 inhibits the pathogenesis of osteoarthritis by targeting leptin and inhibiting the NF-kappaB signaling pathway. PMID: 28627582
7. high gonadal and gonadal-white adipose tissue expression of leptin system was observed in the offspring of dams fed a high fat diet during pregnancy and lactation. PMID: 28759941
8. These results demonstrated that vaspin prevented leptininduced inflammation and catabolism by inhibiting the activation of NFkappa B in rat chondrocytes. PMID: 28677772
9. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following fenugreek seed extract feeding. PMID: 28407664
10. Leptin suppresses glutamate-induced cytotoxicity in primary astrocytes. Leptin inhibits glutamate-induced phosphorylation of ERK1/2 in astrocytes PMID: 29241183
11. A high fat diet not only disturbs normal metabolism, but it also leads to liver inflammation which is obvious by the changes in transaminase activity as well as leptin and hepcidin levels. PMID: 29254298
12. Taken together, our results demonstrated that reduced serum leptin, at least in part, contributes to exercise-mediated improvement of insulin sensitivity, indicating JAK2 as a potent therapeutical target of insulin resistance. PMID: 29294325
13. Leptin expression levels increased in prefrontal cortex and hippocampus following exercise. PMID: 28179125
14. Study establishes that females are more responsive to long-term central leptin overexpression than males and that leptin antagonism has a greater physiological impact in males. PMID: 29044801
15. Results show that, in nonpregnant female rats, central leptin can suppress basal insulin concentrations and lead to impaired glucose tolerance despite unchanged glucose-stimulated insulin secretion. PMID: 27623562
16. Alteration of the neonatal leptin surge in rats can modify the timing of pubertal onset and have long-term effects on hypothalamic expression of reproductive and metabolic neuropeptides. PMID: 27751931
17. Leptin promotes tendon-derived stem cell osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in both vitro and vivo model. PMID: 28407241
18. Hypoxia male offspring had higher plasma leptin from postnatal day (PN) 6 through 14 vs. normoxia pups. PMID: 28957383
19. These data support prior findings suggesting that IL-6 mediates the leptin-sensitizing effects of amylin on VMN neurons and that the inherent leptin resistance of DIO rats can be effectively reversed at a cellular level by IL-6. PMID: 27534878
20. these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D. PMID: 28112679
21. These results suggest that leptin's powerful chronic CNS antidiabetic actions are mediated primarily via nonautonomic mechanisms. PMID: 27923809
22. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their alpha-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development. PMID: 27629888
23. High leptin expression is associated with Hypothyroidism and Hyperthyroidism. PMID: 28097455
24. Data suggest that leptin is involved in mediating the alterations to body energy balance and arcuate nucleus activity following intermittent hypoxia. PMID: 27222924
25. a novel mechanism of leptin-induced fatty acid oxidation in muscle tissue; namely, this process is dependent on the activation of AMPK to induce the translocation of FAT/CD36 to the plasma membrane, thereby stimulating fatty acid uptake. PMID: 27827305
26. High-fat diet combined with chronic stress has a synergistic and adverse effect on visceral adiposity and results in elevated plasma leptin. PMID: 28276709
27. geniposide may regulate tau phosphorylation through leptin signaling PMID: 26496899
28. The reduction of leptin levels by BAPN in vivo and the ability of this compound to inhibit leptin-induced profibrotic mediators and ROS production in cardiac and vascular cells suggest that interactions between leptin and LOX regulate downstream events responsible for myocardial and vascular fibrosis in obesity. PMID: 26780438
29. Results provide evidence that leptin regulates FGF21 expression. PMID: 26982498
30. the activity of JNK stimulated by leptin was suppressed by DUSP19 overexpression. PMID: 26751999
31. Experimental hypothyroidism induced a negative energy balance accompanied by decreased NPY and increased POMC protein content in the arcuate nucleus, resulting in predominance of anorexigenic pathways, and impaired leptin signaling. PMID: 26538454
32. Data indicate a significant decrease of leptin expression in visceral adipose tissue (VAT) 24 hours after surgery. PMID: 26846568
33. Adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels. PMID: 26731409
34. Results demonstrate that cardiac mitochondria express functional leptin receptors suggesting that intracellularly derived leptin functions as an autocrine factor acting on both cell membrane and mitochondrial receptors. PMID: 26122392
35. ventromedial hypothalamus amylin signaling is required for full leptin signaling and protection from high fat diet induced obesity PMID: 26676252
36. our data suggested that leptin enhances the maturity of fetal lungs during hypoxia-induced apoptosis of type II AECs and provide support for the potential of leptin as a therapeutic agent for promoting lung development in Fetal growth restriction . PMID: 25833759
37. leptin regulates lipid metabolism, cytokine production and proliferation of intestinal cells through a mechanism largely dependent on activation of the mTOR pathway. PMID: 26017929
38. the physiological leptin surge occurring around Postnatal Day 9-10 is critical for hippocampal formation development. PMID: 25981175
39. In conclusion, leptin acts within the brain to diminish glucagon secretion during acute hypoglycemia but increases epinephrine, potentially limiting its detrimental effects during hypoglycemia. PMID: 26506851
40. HCG therapy appears to be an effective treatment for endometriosis in rats through down-regulation of leptin expression in eutopic and ectopic endometrium PMID: 25722014
41. Leptin regulates intestinal glutamate transport by different mechanisms. PMID: 25935421
42. the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor, was examined. PMID: 25793389
43. although restoring low plasma leptin levels into the physiological range effectively normalizes increased HPA axis activity in rats with uDM, this effect is neither necessary nor sufficient to explain leptin's antidiabetic action PMID: 26529250
44. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen PMID: 25398524
45. Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet. PMID: 25797953
46. This study demonstrated that the responses of hypothalamic NPY and OBRb mRNA expression to food deprivation develop during the neonatal-prepubertal period and exhibit gender differences in rats. PMID: 25561025
47. results suggest that the insensitivity of PND10 pups to the anorectic effects of leptin might be mediated, at least in part, by a lack of signalling through the Janus kinase/STAT signalling pathway in Ventral Tegmental Area Dopamine neurons. PMID: 25205242
48. Increased Lep and Lep-R expression after prenatal administration of ATRA in nitrofen-induced PH suggests that ATRA may have therapeutic potential in attenuating CDH-associated PH by stimulating alveolarization and de novo surfactant production. PMID: 25330951
49. Serum leptin and liver leptin protein and mRNA expression were increased in a high-fat diet induced model of non-alcoholic steatohepatitis. PMID: 25065280
50. evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death PMID: 25979360

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Secreted.

Leptin family

KEGG: rno:25608

STRING: 10116.ENSRNOP00000066184

UniGene: Rn.44444