Author, as appears in the article.: Vinaixa, Maria; Canelles, Sandra; Gonzalez-Murillo, Africa; Ferreira, Vitor; Grajales, Diana; Guerra-Cantera, Santiago; Campillo-Calatayud, Ana; Ramirez-Orellana, Manuel; Yanes, Oscar; Frago, Laura M; Valverde, Angela M; Barrios, Vicente
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Vinaixa Crevillent, Maria / Yanes Torrado, Óscar
Keywords: Sensitivity Pufa Pathway Pathogenesis Oxidative stress Obesity Modulation Mice, knockout Mice, inbred c57bl Mice Metabolism Lipid metabolism Leptin Irs2−/− mice Irs2 protein, mouse Irs2 Interleukin-1beta Insulin receptor substrate proteins Inhibition Inflammation Hypothalamus Glucose transport proteins, facilitative Fatty acids, unsaturated Expression Energy metabolism Diabetes mellitus, experimental Diabetes Cytokines Chemokine cx3cl1 Blood glucose Animals
Abstract: 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.
Thematic Areas: Medicine (miscellaneous) Cell biology Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all)
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: maria.vinaixa@urv.cat oscar.yanes@urv.cat maria.vinaixa@urv.cat
Author identifier: 0000-0001-9804-0171 0000-0003-3695-7157 0000-0001-9804-0171
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/2073-4409/10/8/2085
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Cells. 10 (8): 2085-
APA: Vinaixa, Maria; Canelles, Sandra; Gonzalez-Murillo, Africa; Ferreira, Vitor; Grajales, Diana; Guerra-Cantera, Santiago; Campillo-Calatayud, Ana; Ramir (2021). Increased Hypothalamic Anti-Inflammatory Mediators in Non-Diabetic Insulin Receptor Substrate 2-Deficient Mice. Cells, 10(8), 2085-. DOI: 10.3390/cells10082085
Article's DOI: 10.3390/cells10082085
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications