Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10082085
Keywords
diabetes; hypothalamus; inflammation; IRS2; mice; PUFA
Categories
Funding
- Spanish Ministry of Science and Innovation
- European FEDER funding [FIS PI19/00166, BFU 2017-82565-C2-1-R, RTI2018-094052-B-100]
- Comunidad de Madrid, Spain [S2017/BMD-3684]
- Network Center for Biomedical Research on Obesity and Nutrition (CIBEROBN) and Diabetes (CIBERDEM) Instituto Carlos III
- CIBEROBN
- Fundacion para la Investigacion Biomedica Hospital Infantil Universitario Nino Jesus
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The research found that non-diabetic IRS2(-/-) mice exhibited elevated anti-inflammatory cytokines in the hypothalamus, while diabetic IRS2(-/-) mice displayed a proinflammatory profile. Additionally, non-diabetic mice showed increased enzyme activity, enhanced lipid synthesis, and elevated levels of polyunsaturated fatty acids.
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.
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