Glyoxalase 1 Knockout Promotes Age- and Sex-dependent Obesity and Metabolic Dysfunction
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA484131 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glyoxalase 1 (Glo1) is a critical enzyme responsible for the clearance of toxic dicarbonyls, which modify proteins to produce advanced glycation end products (AGEs). Glo1 has been recently implicated in the progression of metabolic disorders, however underlying mechanisms are poorly understood. We aim to investigate the role of Glo1 in metabolic perturbations and determine whether AGEs mediate the Glo1 activities in obesity and metabolic health.
2018-08-03 | GSE118034 | GEO
Project description:Age and obesity associated immune dysfunction mammary tumor growth
| PRJNA1136456 | ENA
Project description:It is unclear whether liver dysfunction is implicated in obesity-related detrimental changes in brain structure and function. This study examineed associations between liver dysfunction and brain health in middle-aged participants with obesity and early-stage metabolic dysfunction-associated steatotic liver disease (MASLD). Using brain magnetic resonance imaging, neuropsychological tests, histological and biochemical characterization of liver biopsies, we showed that specific hallmarks of liver dysfunction (e.g. free cholesterol accumulation, early fibrosis) are associated with increased white matter hyperintensities and larger variations in cerebral blood flow indicating poorer cerebrovascular function. These associations were independent of age, sex, body mass index, diabetes and hypertension and corroborated by independent liver RNA-seq and pathway analysis highlighting the role of liver inflammation and cellular stress. Further associations with circulating IL-6 suggest systemic low-grade inflammation as potential mediator between liver and brain. Hence, in obesity at midlife, cerebrovascular health is independently associated with the pathological state of the liver.
2024-09-30 | GSE249997 | GEO
Project description:KDM4B epigenetically protects against obesity and metabolic dysfunction
| PRJNA397224 | ENA
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex- and age-associated mechanisms underlying the pathophysiology remain poorly understood. Here we show distinct responses to a HFD between males and females. Our study underscores the need for utilizing both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals. Hepatology Communications 2024
2024-09-03 | GSE274914 | GEO
Project description:Transcriptome data of monocytes from adolescents with obesity and age / sex matched controls
| PRJNA939519 | ENA
Project description:Pneumosepsis survival in the setting of obesity leads to persistent steatohepatitis and metabolic dysfunction.
2023-05-02 | GSE231504 | GEO
Project description:Maternal obesity is a growing health concern that predisposes offspring to metabolic dysfunction, immune system alterations, and neurodegenerative disorders. To investigate the intergenerational effects of maternal obesity, we used Drosophila melanogaster models exposed to high-sugar (HSD) and high-fat diets (HFD). We found that maternal diet-induced obesity significantly altered offspring lifespan, immune function, and neuronal health in a sex- and diet-specific manner. Male offspring were particularly susceptible, exhibiting reduced lifespan, impaired climbing ability, and increased axonal degeneration, especially following maternal HFD exposure. Transcriptomic analyses revealed age-dependent and diet-specific changes, with males showing pronounced alterations at 50 days of age. Developmental programming of hemocytes (macrophage-like cells) played a crucial role in these outcomes, as knockdown of key immune pathways such as Relish and Upd3 in hemocytes further influenced lifespan in a diet-specific manner. These findings highlight the complex interplay between maternal diet and immune function, underscoring the importance of immune cells in mediating the long-term health consequences of maternal obesity. Our study provides new insights into conserved mechanisms linking maternal metabolic health to offspring outcomes and emphasizes the continued need for animal models to understand intergenerational health impacts.
2024-12-23 | GSE284632 | GEO
Project description:From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the spag7 gene linked to metabolic dysfunction in mice. Here we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a “thrifty phenotype” is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.
2023-11-01 | GSE246428 | GEO
Project description:In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice. In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice.
2025-06-30 | PXD029562 | Pride