Increased Hypothalamic Anti-Inflammatory Mediators in Non-Diabetic Insulin Receptor Substrate 2-Deficient Mice

Autor: María Vinaixa, Sandra Canelles, África González-Murillo, Vítor Ferreira, Diana Grajales, Santiago Guerra-Cantera, Ana Campillo-Calatayud, Manuel Ramírez-Orellana, Óscar Yanes, Laura M. Frago, Ángela M. Valverde, Vicente Barrios
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cells, Vol 10, Iss 8, p 2085 (2021)
Druh dokumentu: article
ISSN: 10082085
2073-4409
DOI: 10.3390/cells10082085
Popis: 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 anti-inflammatory profile, increased insulin sensitivity and polyunsaturated fatty acids content in the hypothalamus may slow down or delay the onset of diabetes.
Databáze: Directory of Open Access Journals
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