Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/1589
Title: Chronic stress combined with a fructose diet reduces hypothalamic insulin signaling and antioxidative defense in female rats
Authors: Kovačević, Sanja
Nestorov, Jelena
Matić, Gordana 
Elaković, Ivana
Keywords: Appetite;Female rats;Glucocorticoid receptors;Inflammation;Insulin;Leptin
Issue Date: 1-Jun-2019
Rank: M21a
Journal: Neuroendocrinology
Abstract: 
© 2018 S. Karger AG, Basel. Background: Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio-melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Objectives: We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. Methods: Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. Results: Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. Conclusions: Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative -defense, and inflammatory responses of this homeostasis- regulating center.
URI: https://biore.bio.bg.ac.rs/handle/123456789/1589
ISSN: 0028-3835
DOI: 10.1159/000496391
Appears in Collections:Journal Article

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