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Objectives: Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here, we analyze whether the early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. Methods: Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction was performed to determine expression in the hypothalamus of agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript. Plasma estradiol, testosterone, and adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and leptin were measured by mulitplex immunoassays. Results: Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels, and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol, and acylated ghrelin levels. Discussion: Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism. [ABSTRACT FROM AUTHOR]

Summary: Background: Insulin resistance (IR) in children with obesity constitutes a risk factor that should be precisely diagnosed to prevent further comorbidities. Objective: Chemokines were evaluated to identify novel predictors of IR with clinical application. Methods: We analysed the levels of cytokines (tumour necrosis factor [TNF] α and interleukins [ILs] 1β, 4, 6 and 10), chemokines (stromal cell derived factor 1α, monocyte chemoattract protein [MCP] 1, eotaxin and fractalkine) and growth factors (brain‐derived neurotrophic factor, pro‐fibrotic platelet‐derived growth factor [PDGF‐BB] and insulin‐like growth factor 1) in serum of prepubertal children with obesity (61 girls/59 boys, 50% IR and 50% non‐IR) and 32 controls. Factor analysis, correlation, binary logistic regression and receiver operating characteristic analysis of combined biomarkers were used to validate their capability for preventive interventions of IR. Results: Changes in MCP1, eotaxin, IL1β and PDGF‐BB were observed in IR children with obesity. Bivariate correlation between stromal cell derived factor 1α, MCP1, eotaxin, TNFα, brain‐derived neurotrophic factor and/or PDGF‐BB explained the high variance (65.9%) defined by three components related to inflammation and growth that contribute towards IR. The combination of leptin, triglyceride/high‐density lipoprotein, insulin‐like growth factor 1, TNFα, MCP1 and PDGF‐BB showed a sensitivity and specificity of 93.2% for the identification of IR. The percentage of correct predictions was 89.6. Conclusions: Combined set of cytokines, adipokines and chemokines constitutes a model that predicts IR, suggesting a potential application in clinical practice as biomarkers to identify children with obesity and hyperinsulinaemia. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to evaluate the influence of HFD on the functionality of LepR by quantifying phosphorylated levels of 705Tyr-STAT3 in hippocampus astrocytes from mice that consumed an HFD either during the juvenile or the adult period., Methods: Five- and eight-week-old male mice, fed during 8 weeks with either control chow or HFD, received a single dose of leptin and their brains were prepared for immunofluorescence to identify double-positive GFAP/p705Tyr-STAT3 cells., Results: HFD intake led to increased pSTAT3 immunoreactivity in GFAP+ cells in the CA1/CA3 hippocampus areas. The effect was observed both in adolescent and adult mice. Leptin increased pSTAT3 immunoreactivity in control animals but was devoid of effect in HFD mice. HFD itself has no effect on the number of GFAP+ cells., Conclusions: Our data show that regular intake of HFD enhances STAT3 signaling in CA1/CA3 astrocytes, an effect that could be linked to the increase of leptin triggered by HFD. The increase of pSTAT3 might be integral to homeostatic mechanisms aimed at maintaining hippocampus function., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Oxidative stress has been proposed to be a pathogenic mechanism to induce endothelial dysfunction and the onset of cardiovascular disease. Elevated levels of free fatty acids can cause oxidative stress by increasing mitochondrial uncoupling but, at physiological concentrations, they are essential for cell and tissue function and olive oil free fatty acids have proved to exhibit beneficial effects on risk factors for cardiovascular disease. We hypothesize that realistic concentrations within the physiological range of oleic (OA) and palmitic (PA) acids could be beneficial in the prevention of oxidative stress in vascular endothelium. Hence, pre-treatment and co-treatment with realistic physiological doses of palmitic and oleic acids were tested on cultured endothelial cells submitted to a chemically induced oxidative stress to investigate their potential chemo-protective effect. Cell viability and markers of oxidative status: reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPx) and glutathione reductase (GR) were evaluated. As a conclusion, the increased ROS generation induced by stress was significantly prevented by a pre- and co-treatment with PA or OA. Moreover, pre- and co-treatment of cells with FFAs recovered the stress-induced MDA concentration to control values and significantly recovered depleted GSH and normalized GPx and GR activities. Finally, pre- and co-treatment of cells with physiological concentrations of PA or OA in the low micromolar range conferred a substantial protection of cell viability against an oxidative insult.