Comprehensive microarray analysis for the identification of therapeutic targets within HIF-1α signalling networks in diet-induced obesity via hypothalamic inflammation

Archives of Endocrinology and Metabolism, Год журнала: 2025, Номер 69, С. 1 - 17

Опубликована: Янв. 1, 2025

A high-fat diet (HFD) significantly contributes to obesity and alters the neurological function of brain. This study explored influence hypoxia-inducible factor (HIF-1) its downstream molecules on progression in context HFD-induced hypothalamic inflammation. Utilizing a bioinformatics approach alongside animal models, targets pathways related were identified via network analysis, gene target identification, ontology Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment, subsequent validation models. HIF-1α has potential regulate immune response by promoting infiltration increasing population cells, particularly memory CD4 T hypothalamus, primarily through ksr2 expression. Additionally, analysis predicted five drugs capable enhancing HIF-1-Ksr2 signalling. In conclusion, targeting Ksr2 with specific represents for addressing obesity. These novel findings lay groundwork developing dietary supplements therapeutic interventions.

Язык: Английский

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Metabolic Clues to Memory Loss: High-Fat Diets and Brain-Adipose Crosstalk in Zebrafish

Behavioural Brain Research, Год журнала: 2025, Номер unknown, С. 115559 - 115559

Опубликована: Март 1, 2025

Язык: Английский

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Chromium and formoterol therapy for obesity-induced asthma in rats

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

The development of asthma is impacted by fat. Asthma more common in obese persons. purpose the experimental study to determine how chromium, formoterol, and their combination can improve quality life for people with lung anomalies. Thirty-six male Wistar rats were divided into six groups: control (C), obesity (CO), obese-asthma (COA), groups treated formoterol (OAF), chromium (OACR), or both (OACRF). Except group C, all received a high-fat diet 4 weeks. Subsequently, ovalbumin (OVA) was administered subcutaneously (s.c.) except C CO induce sensitization. triggered via 1% OVA aerosol challenges on days 26-28. Over 5 days, OAF OACRF daily inhalations (50 μg/kg), while OACR given (400 μg/kg). Treatments timed align induction protocols. Lipid profile inflammatory indicators examined at end trial-Immunohistochemical analysis tissue, Histopathological tissue stained Hematoxylin Eosin. therapy (OACRF) significantly reduced body weight (p < 0.05), lowered LDL triglycerides, increased HDL, normalized architecture compared controls. Immunohistochemistry revealed IL-1β IL-17α expression. demonstrated superior reducing weight, improving indicators, restoring its normal state administering therapy. most effective strategy treating address two connected conditions. These findings demonstrate that combined effectively addresses metabolic components obesity-induced asthma, offering promising dual-target therapeutic strategy.

Язык: Английский

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From fat to filter: the effect of adipose tissue-derived signals on kidney function

Nature Reviews Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Язык: Английский

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Novel Thyroid Hormone Receptor-β Agonist TG68 Exerts Anti-Inflammatory, Lipid-Lowering and Anxiolytic Effects in a High-Fat Diet (HFD) Mouse Model of Obesity

Cells, Год журнала: 2025, Номер 14(8), С. 580 - 580

Опубликована: Апрель 11, 2025

Recent advances in drug development allowed for the identification of THRβ-selective thyromimetic TG68 as a very promising lipid lowering and anti-amyloid agent. In current study, we first investigated neuroprotective effects on vitro human models neuroinflammation β-amyloid neurotoxicity order to expand our knowledge therapeutic potential this novel thyromimetic. Subsequently, examined metabolic inflammatory profiles, along with cognitive changes, using high-fat diet (HFD) mouse model obesity. Our data demonstrated that was able prevent either LPS/TNFα-induced response or β-amyloid-induced cytotoxicity microglial (HMC3) cells. Next, HFD-fed mice, treatment (10 mg/kg/day; 2 weeks) significantly reduced anxiety-like behavior stretch–attend posture (SAP) tests while producing 12% BW loss significant decrease blood glucose levels. Notably, these highlight close relationship between improved serum parameters reduction anxious behavior. Moreover, administration observed efficiently counteract HFD-altered central peripheral expressions mice selected biomarkers dysfunction, inflammation, neurotoxicity, revealing effects. conclusion, work provides preliminary evidence may represent opportunity interlinked diseases such obesity neurodegenerative diseases.

Язык: Английский

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Functional Relationship between Inhibitory Control, Cognitive Flexibility, Psychomotor Speed and Obesity

Brain Sciences, Год журнала: 2022, Номер 12(8), С. 1080 - 1080

Опубликована: Авг. 15, 2022

In the last decades, it has been proposed that executive functions may be particularly vulnerable to weight-related issues. However, evidence on matter is mixed, especially when effects of sociodemographic variables are weighted. Thus, current study aimed at further examining relationship between and obesity. To this aim, we compared treatment-seeking overweight, obese, morbidly obese patients with normal-weight control participants. We examined general functioning (Frontal Assessment Battery−15) different subdomains (e.g., inhibitory control, verbal fluency, psychomotor speed) in a clinical sample including 208 outpatients degrees BMI (52 25−30, M age = 34.38; 76 30−40, 38.00; 80 > 40, 36.20). Ninety-six subjects served as controls. No difference scores was detected were over- or subjects. Morbidly reported lower performance than Between-group emerged also relevant covariates taken into account. Our results support view morbid obesity associated performance, considering critical role exerted by (i.e., sex, age, education) variables. should accounted management patient because non-negligible relevance diagnostic, therapeutic, prognostic terms.

Язык: Английский

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Sex differences in the effects of high fat diet on underlying neuropathology in a mouse model of VCID

Biology of Sex Differences, Год журнала: 2023, Номер 14(1)

Опубликована: Май 19, 2023

Abstract Background Damage to the cerebral vasculature can lead vascular contributions cognitive impairment and dementia (VCID). A reduction in blood flow brain leads neuropathology, including neuroinflammation white matter lesions that are a hallmark of VCID. Mid-life metabolic disease (obesity, prediabetes, or diabetes) is risk factor for VCID which may be sex-dependent (female bias). Methods We compared effects mid-life between males females chronic hypoperfusion mouse model C57BL/6J mice were fed control high fat (HF) diet starting at ~ 8.5 months age. Three after initiation, sham unilateral carotid artery occlusion surgery (VCID model) was performed. later, underwent behavior testing brains collected assess pathology. Results have previously shown this model, HF causes greater wider array deficits males. Here, we report on sex differences underlying specifically changes several areas brain. White negatively impacted by females, with correlating less myelin markers only. High led an increase microglia activation but not females. Further, decrease proinflammatory cytokines pro-resolving mediator mRNA expression Conclusions The current study adds our understanding neuropathology presence common (obesity/prediabetes). This information crucial development effective, sex-specific therapeutic interventions

Язык: Английский

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Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Апрель 17, 2023

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes produce various pro-inflammatory molecules. These molecules cause low-intensity inflammation, affecting organism’s functioning central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during occurs different structures CNS involved memory learning, such cortex hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect physiology, neuroinflammation promoting cellular senescence establishment. Since some studies have shown an increase senescent cells aging, obesity, neurodegenerative diseases, proposed participation may contribute cognitive decline model middle-aged female Wistar rats. inflammatory state 6 13 months-old rats fed hypercaloric diet was measured serum (cortex hippocampus). Memory evaluated using novel object recognition (NOR) test; presence markers also determined. Our data suggest systemic generated by induces regions learning memory, markers, thus proposing potential participant negative consequences cognition.

Язык: Английский

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Adiponectin and resistin modulate the progression of Alzheimer´s disease in a metabolic syndrome model

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Сен. 4, 2023

Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk several aging-related brain diseases, including Alzheimer's disease (AD). However, underlying mechanism explaining link between MetS function is poorly understood. Among possible mediators are adipose-derived secreted molecules called adipokines, adiponectin (ApN) resistin, which have been shown to regulate by modulating processes. To investigate impact adipokines on MetS, we employed diet-induced model induce various complications associated with MetS. For this purpose, administered high-fat diet (HFD) both WT APP/PSN1 mice at pre-symptomatic stage. Our data showed causes fast decline in cognitive performance stimulates Aβ42 production brain. Interestingly, ApN treatment restored glucose metabolism improved functions 50% while decreasing Aβ42/40 ratio approximately 65%. In contrast, resistin exacerbated Aβ pathology, increased oxidative stress, strongly reduced metabolism. Together, our demonstrate alterations could further contribute AD pathology.

Язык: Английский

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Visceral and Subcutaneous Abdominal Fat Predict Brain Volume Loss at Midlife in 10,001 Individuals

Aging and Disease, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

Abdominal fat is increasingly linked to brain health. A total of 10,001 healthy participants were scanned on 1.5T MRI with a short whole-body MR imaging protocol. Deep learning FastSurfer segmented 96 regions. Separate models visceral and subcutaneous abdominal fat. Regression analyses types normalized volumes evaluated, controlling for age sex. Logistic regression determined the risk gray white matter volume loss from highest quartile lowest these volumes. This cohort had an average 52.9 ± 13.1 years 52.8% men 47.2% women. Segmented predicted lower in multiple regions including: (r = -.44, p<.001), =-.41, hippocampus -.39, p< .001), frontal cortex -.42, temporal lobes parietal occipital =-.37, p<.001). Women showed than related increased Visceral (age 20-39: OR 5.9; 40-59, 5.4; 60-80, 5.1) low volume: 3.78; 4.4; 5.1). Higher loss. Elevated may represent novel modifiable factors determining

Язык: Английский

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