LEP是一種由脂肪細(xì)胞分泌的多肽激素，全名為瘦素。近年來(lái)，對(duì)LEP的研究引起了廣泛關(guān)注。研究發(fā)現(xiàn)，LEP參與調(diào)節(jié)食欲、代謝和能量平衡等生理過(guò)程，并與肥胖、糖尿病等代謝性疾病的發(fā)生和發(fā)展密切相關(guān)。

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 cells proliferation and reduces autophagy during TCR (T cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.

1. In C57bl/6 model, glycaemic index of maternal dietary carbohydrates differentially alters Fto and Lep expression in offspring. PMID: 30241328
2. A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models PMID: 29217773
3. Catalase overexpression modulates metabolic parameters in a new 'stress-less' leptin-deficient mouse model. PMID: 28645653
4. Since upregulation of ANGPTL6 is induced on metabolic stress, we investigated the hepatic expression of ANGPTL6 by leptin, a representative adipokine of obesity. Mice on a high-fat diet showed increased serum leptin levels and hepatic Angptl6 expression. PMID: 29852166
5. This study shows that prolonged exposure to high-fat diets in adulthood is associated with a gradually increasing DNA methylation level at the Leptin and Pparg2 promoters in a depot-specific manner. PMID: 28256596
6. the study reports a novel mechanistic pathway of leptin-mediated renal inflammation that is dependent on NOX-2-miR21 axis in ectopic manifestations underlying non-alcoholic fatty liver disease-induced co-morbidities PMID: 29660503
7. These results demonstrated a novel molecular mechanism by which leptin sustained oligodendrocyte precursor cell proliferation and remyelination in a pathological central nervous system. PMID: 28091609
8. These data demonstrate that FAAH activity is required for leptin's hypophagic effects PMID: 29967158
9. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid-sensing system in adipocytes. PMID: 29891714
10. These results indicate that leptin plays a role in nociception induced by acute inflammation PMID: 29204732
11. results suggest that STAT transcriptional activity is downregulated by high levels of leptin, leading to reduced cAMP-dependent steroidogenic genes (Star and Cyp11a1) expressions in MA-10 Leydig cells. PMID: 28343310
12. Data suggest that lnc-leptin is among the most prominent lncRNAs expressed in adipocytes; lnc-leptin expression from an enhancer region upstream of leptin is sensitive to insulin and correlates to leptin expression across diverse pathophysiological conditions; induction of lnc-leptin is essential for adipogenesis; its presence is required for maintenance of leptin expression in adipocytes. (lnc = long non-coding RNA) PMID: 29519872
13. Data (including data from studies using mutant, transgenic, and knockout mice) suggest that gene targets of leptin/leptin-receptor (Lep/Lepr) signaling in hypothalamic neurons regulate energy metabolism; Lep/Lepr signaling appears to up-regulate expression of Atf3 (activating transcription factor-3) in hypothalamic neurons. PMID: 29535089
14. Study shows that compared to the other mouse lines, db/db mice with dysfunctional leptin receptors had a significantly longer tail flick latency after saline and buprenorphine. The results provide novel support for the interpretation that acute thermal nociception is associated with altered leptin signaling. PMID: 28893589
15. The studies established a potential link between leptin and adipocyte insulin responsiveness in an NOS2 dependent manner. PMID: 28739528
16. leptin regulates the expression of osteocalcin in growth plate chondrocytes via the ERK1/2 signaling pathway, while there is no effect on the phosphorylation of either p38 or AKT PMID: 27564111
17. Hyperleptinemia exacerbates high fat diet-mediated atrial fibrosis and atrial fibrillation. PMID: 28257569
18. Taken together, these results suggest that leptin, in concert with other stimuli in the micro milieu, may contribute to the development of psoriasis. PMID: 27488462
19. Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health. PMID: 27791019
20. t the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease. PMID: 27588900
21. in congenitally leptin deficient animals, leptin is not required for compensatory reduction in energy expenditure accompanying weight loss, but suggest that the hyperphagia of the weight-reduced state is leptin-dependent. PMID: 29261744
22. Our data provide evidence that the interplay of these two hormones could help improve the understanding of the pathogenesis of atherosclerosis and NAFLD. PMID: 29158088
23. Data suggest that Htr2c and leptin in hypothalamic nuclei may be involved in the effects of corticosterone on food intake/appetite regulation. (Htr2c = 5-hydroxytryptamine type 2C receptor) PMID: 28186389
24. Further experiments indicated that miR-122 inhibited leptin-induced liver fibrosis in leptin-deficient mouse model. PMID: 29054053
25. Endoplasmic reticulum stress-induced CHOP activation in the brain is a mechanistic link in the palmitate-induced negative regulation of leptin and IGF1. PMID: 27555288
26. neuronal Rap1 critically regulates leptin sensitivity PMID: 27626668
27. Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1(+) progenitor cells via leptin receptor-dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal-regulated kinase)-FAK pathways, which enhanced neointimal formation. PMID: 28935755
28. Depletion of CLPABP disturbed the normal subcellular localization of HuR to stress granules, and overexpression of CLPABP induced instability of leptin mRNA by inhibiting HuR function. PMID: 27616329
29. These results confirm and extend the previous evidence that LEP has a general and important role in the response of mammalian cells to irradiation. PMID: 28593811
30. leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain after avulsion of the cervical roots. PMID: 28822786
31. Suggest that intact endothelial leptin signaling limits neointima formation and that obesity represents a state of endothelial leptin resistance. PMID: 28705795
32. 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
33. High fat diet attenuates leptin signaling throughout the brain, but some brain regions maintain their ability to sense leptin. Weight loss restores leptin sensing to some degree in most (but not all) brain regions, while other brain regions display hypersensitivity to leptin following weight loss PMID: 28107353
34. CNS-specific Tak1 deletion prevented ER-stress-induced hypothalamic leptin resistance and hyperphagic obesity under a high-fat diet (HFD). Thus, TAK1 is a crucial regulator of ER stress in vivo, which could be a target for alleviation of ER stress and its associated disease conditions. PMID: 26985063
35. these data unmasked a role for mitochondrial fission in leptin sensitivity and glucose sensing of POMC neurons. PMID: 28190775
36. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance. PMID: 27782940
37. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negativ PMID: 28100475
38. genetic and pharmacological ablation of adult NG2-glia (also known as oligodendrocyte precursors), but not microglia, leads to primary leptin resistance and obesity in mice. PMID: 27166944
39. 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
40. Results demonstrate that in white adipose tissue, leptin expression and secretion is promoted by Epac1, hence regulating energy balance and glucose homeostasis. PMID: 27381457
41. may regulate growth hormone expression in somatotropes through the stimulation of POU1F1 PMID: 27571135
42. This study found that the expression of leptin and its receptor OB-R in mouse models of Sjogren's syndrome are elevated both locally and systemically during Sjogren's syndrome progression. PMID: 27889607
43. obesity-associated elevation of leptin contributes to the increased susceptibility of asthma via modulation of pro-allergic lymphocyte responses. PMID: 27566543
44. Leptin stimulation led to TNFalpha production under both in vitro and in vivo conditions, and diurnal fluctuation of leptin concentrations in the cerebrospinal fluid predicted the circadian changes of TNFalpha gene expression in the hypothalamus. PMID: 27226618
45. geniposide may regulate tau phosphorylation through leptin signaling PMID: 26496899
46. Activated FXR inhibits leptin signaling and counteracts tumor-promoting activities of cancer-associated fibroblasts in breast malignancy. PMID: 26899873
47. this study shows that knockdown of leptin in hepatoma cells caused higher Treg activity and lower CD8+ T-cell response in the mouse hepatocellular carcinoma allograft model. PMID: 26639061
48. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus. PMID: 26859361
49. The weight-reducing hypophagic effects of leptin are not augmented through its thermogenic effect. PMID: 26876182
50. ime-specific changes in promoter associated DNA methyltransferases may be associated with the regulation of leptin expression. PMID: 25433105

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Defects in Lep are the cause of profound obesity and type II diabetes.

Secreted.

Leptin family

KEGG: mmu:16846

STRING: 10090.ENSMUSP00000067046

UniGene: Mm.277072