Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Semaphorins and their receptors (plexins) are axon-guiding molecules that regulate the development of the nervous system during embryogenesis. Here we describe a previously unknown role of class 3 semaphorin E (Sema3E) in adipose tissue inflammation and insulin resistance. Expression of Sema3E and its receptor plexinD1 was upregulated in the adipose tissue of a mouse model of dietary obesity. Inhibition of the Sema3E-plexinD1 axis markedly reduced adipose tissue inflammation and improved insulin resistance in this model. Conversely, overexpression of Sema3E in adipose tissue provoked inflammation and insulin resistance. Sema3E promoted infiltration of macrophages, and this effect was inhibited by disrupting plexinD1 expression in macrophages. Disruption of adipose tissue p53 expression led to downregulation of Sema3E expression and improved adipose tissue inflammation. These results indicate that Sema3E acts as a chemoattractant for macrophages, with p53-induced upregulation of Sema3E expression provoking adipose tissue inflammation and systemic insulin resistance in association with dietary obesity.
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PMID:Semaphorin3E-induced inflammation contributes to insulin resistance in dietary obesity. 2409 72

We previously demonstrated that cellular aging signals upregulated a secreted class 3 semaphorin E (Sema3E) and its receptor plexinD1 in the adipose tissue of a murine model of dietary obesity and that Sema3E was a chemoattractant, mediating its biological effects by inducing infiltration of plexinD1-positive inflammatory macrophages into the visceral white adipose tissue. This study was performed to develop a peptide vaccine for Sema3E and test its therapeutic potential in a murine model of dietary obesity. Two antigenic peptides were selected to generate neutralizing antibodies for a vaccine. These peptides were conjugated to keyhole limpet hemocyanin (KLH), and were administered with Freund's adjuvant to obese wild-type male mice. The Sema3E antibody titer was analyzed by ELISA, and the biological effects of the peptides were tested in mice with dietary obesity. Among the two candidate peptides, the Sema3E antibody titer was significantly increased by injection of KLH-conjugated HKEGPEYHWS (Sema3E vaccine). Administration of Sema3E vaccine suppressed the infiltration of plexinD1-positive cells, ameliorated chronic inflammation in visceral white adipose tissue, and improved systemic glucose intolerance in mice with dietary obesity, suggesting that Sema3E vaccine has the potential to become a next generation therapy for obesity and diabetes.
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PMID:Peptide vaccine for semaphorin3E ameliorates systemic glucose intolerance in mice with dietary obesity. 3084 54