Increased hypothalamic anti‐inflammatory mediators in non‐diabetic insulin receptor substrate 2‐deficient mice
EntityUAM. Departamento de Pediatría
10.3390/cells10082085Cells 10.8 (2021): 2085
Funded byThis work was supported by the Spanish Ministry of Science and Innovation with the help of European FEDER funding (grant numbers FIS PI19/00166, BFU 2017-82565-C2-1-R, and RTI2018-094052-B-100), Comunidad de Madrid, Spain (S2017/BMD-3684) and the Network Center for Biomedical Research on Obesity and Nutrition (CIBEROBN) and Diabetes (CIBERDEM) Instituto Carlos III. S.C. was supported by CIBEROBN and A.G.M. by Fundación para la Investigación Biomédica Hospital Infantil Universitario Niño Jesús
ProjectGobierno de España. PI19/00166; Gobierno de España. BFU 2017-82565-C2-1-R; Gobierno de España. RTI2018-094052-B-100; Comunidad de Madrid. S2017/BMD-3684 MOIR2-CM
SubjectsDiabetes; Hypothalamus; Inflammation; IRS2 mice −/−; PUFA; Medicina
Rights© 2021 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
Insulin receptor substrate (IRS) 2 is a key mediator of insulin signaling and IRS‐2 knockout (IRS2−/−) mice are a preclinical model to study the development of diabetes, as they develop peripheral insulin resistance and beta‐cell failure. The differential inflammatory profile and insulin signaling in the hypothalamus of non‐diabetic (ND) and diabetic (D) IRS2−/− mice might be implicated in the onset of diabetes. Because the lipid profile is related to changes in inflammation and insulin sensitivity, we analyzed whether ND IRS2−/− mice presented a different hypothalamic fatty acid metabolism and lipid pattern than D IRS2−/− mice and the relationship with inflammation and markers of insulin sensitivity. ND IRS2−/− mice showed elevated hypothalamic anti‐inflammatory cytokines, while D IRS2−/− mice displayed a proinflammatory profile. The increased activity of enzymes related to the pentose‐phosphate route and lipid anabolism and elevated polyunsaturated fatty acid levels were found in the hypothalamus of ND IRS2−/− mice. Conversely, D IRS2−/− mice have no changes in fatty acid composition, but hypothalamic energy balance and markers related to anti‐inflammatory and insulin‐sensitizing properties were reduced. The data suggest that the concurrence of an antiinflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.
Google Scholar:Vinaixa, María - Canelles, Sandra - González‐Murillo, África - Ferreira, Vítor - Grajales, Diana - Guerra-Cantera, Santiago - Campillo‐Calatayud, Ana - Ramírez‐Orellana, Manuel - Yanes, Óscar - Frago Fernández, Laura María - Valverde, Ángela M. - Barrios, Vicente
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