Substance P (SP)-Neurokinin-1 Receptor (NK-1R) Alters Adipose Tissue Responses to High-Fat Diet and Insulin Action
| Autor: | Iordanes Karagiannides, Miriam A Nuno, Dimitris Stavrakis, James M. Bugni, Norma P. Gerard, Bao Lu, Susan E. Leeman, Kyriaki Bakirtzi, Efi Kokkotou, Tamara Pirtskhalava, James L. Kirkland, Charalabos Pothoulakis, Collin Bowe, Hamed Nayeb-Hashemi |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Leptin
Male medicine.medical_specialty Glucose uptake medicine.medical_treatment Adipose tissue Substance P Biology Carbohydrate metabolism Weight Gain Mice Endocrinology Insulin resistance Internal medicine medicine Animals Humans Insulin Obesity Mice Knockout Adiponectin receptor 1 Diabetes-Insulin-Glucagon-Gastrointestinal Receptors Neurokinin-1 medicine.disease Dietary Fats Rats Inbred F344 Rats Mice Inbred C57BL Insulin receptor Glucose Adipose Tissue biology.protein Female Signal Transduction |
| Zdroj: | Endocrinology. 152:2197-2205 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2010-1345 |
| Popis: | 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 Cθ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|