Substance P as a Novel Anti-obesity Target

Καραγιαννίδης, Ιορδάνης; Torres, Daniel; Tseng, Yu–Hua; Bowe, Collin; Carvalho, Eugénia; Espinoza, Daniel; Pothoulakis, Charalabos; Kokkotou, Efi

doi:10.1053/j.gastro.2007.12.032

Cited by 56 publications

(71 citation statements)

References 43 publications

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“…Capsaicin-sensitive nerves coexpress SP with CGRP, and mice whose NK1Rs were deleted by genetic recombination show protection against dietinduced weight gain comparable to that seen in the CGRP knockout animals (Karagiannides et al, 2011). This protective effect was replicated by NK1R antagonists (Karagiannides et al, 2008;Ramalho et al, 2013). It is worth mentioning here that obesity is a recognized risk factor for migraine and it was speculated that CGRP may be the molecular link between these two disorders (Recober and Goadsby, 2010).…”

Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 77%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

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Section: E Transient Receptor Potential Channels In Obesity and Metamentioning

confidence: 77%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

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“…Pituitary adenylate cyclase activating polypeptide (PACAP), sensory fiber substance P (SP) and sympathetic neuropeptide Y (NPY) are co-transmitters in the process of neuronal signal transmission and both PACAP and SP have been shown to have an impact upon the insulin sensitivity of adipocytes [110]. With regards to NPY, studies have mainly focused upon the influence upon glucose metabolism in adipocytes.…”

Section: The Characteristics Of Human Npy Receptorsmentioning

confidence: 99%

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

et al. 2017

Cell Physiol Biochem

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Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

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“…Administration of the NK-1R nonpeptide receptor antagonist CJ 12,255 leads to reduced weight gain in response to high-fat feeding as well as to increased weight loss in models of diet-induced and genetic obesity (ob/ob) in mice (20). Here, we used NK-1R KO mice to investigate the effects of NK-1R deficiency in response to HFD as well as weight-associated metabolic responses.…”

Section: Nk-1r Ko Mice Gain Less Weight In Response To Hfd Compared Wmentioning

confidence: 99%

“…We have recently demonstrated the ability of SP to induce proinflammatory responses in human mesenteric preadipocytes via binding to NK-1R receptor (9). The proinflammatory potential of SP (9), coupled with the beneficial effects of NK-1R pharmacologic antagonism on weight gain and glucose clearance (20), led us to investigate whether SP can directly affect insulin sensitivity in isolated fat cells.…”

mentioning

confidence: 99%

Substance P (SP)-Neurokinin-1 Receptor (NK-1R) Alters Adipose Tissue Responses to High-Fat Diet and Insulin Action

et al. 2011

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Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase C activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.

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Substance P as a Novel Anti-obesity Target

Cited by 56 publications

References 43 publications

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

Substance P (SP)-Neurokinin-1 Receptor (NK-1R) Alters Adipose Tissue Responses to High-Fat Diet and Insulin Action

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