Dataset Information

Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

ABSTRACT: Kidney structural integrity is critical for bodily excretory mechanism. Diabetes has been considered as one of the major risk factors for chronic kidney disease, but the underlying mechanism remains elusive. The present study investigates the transcriptomic and proteomic profiling of long-term impact of high-fat diet (HFD) on renal tissue in mice and role of dehydrozingerone (DH) in reinstating the normal kidney function. Animals were divided into four groups- healthy (NCD+Veh), diabetic (HFD-STZ+Veh), healthy+DH (NCD+Veh+DH) and treatment (HFD-STZ+DH). 65th days of HFD-fed C57BL/6 mice developed diabetes and kidney dysfunction evident by albuminuria, proteinuria, and glucotoxicity with accumulation of glucose, triglyceride, cholesterol, albumin, and total protein in blood serum. The HFD-fed kidney showed renal injuries, including prominent defects in the glomerular filtration system by downregulation of proteins involved in transport, metabolic process, energy production, anti-oxidation, etc. Downregulation of lipid metabolism is the most impacted metabolic process under diabetic condition. Downregulation of transport proteins mainly impact the functioning of podocytes, cell adhesion and cytoskeletal rearrangement. HFD feeding also increased oxidative stress and induced mitochondrial dysfunction, and thereby activating the pro-apoptotic pathway. Progression of DNA damage under diabetic condition triggered the epigenetic alteration and subsequent downstream changes which is evident by activation of HDAC1 under diseased condition. Transcriptomic study revealed the potential of dehydrozingerone in attenuating the diabetic condition by positively regulating transport system, mitochondrial function, lipid metabolism, DNA damage and epigenetic alteration, and oxidative stress, which ameliorate the kidney function.

ORGANISM(S): Mus musculus

PROVIDER: GSE290410 | GEO | 2025/03/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The incidence of type 2 diabetes (T2D) is increasing globally, with long-term implications for human health and longevity. Heart disease is the leading cause of death in T2D patients, who display an elevated risk of an acute cardiovascular event and worse outcomes following such an insult. The underlying mechanisms that predispose the diabetic heart to this poor prognosis remain to be defined. This study developed a pre-clinical model (Rattus norvegicus) that complemented caloric excess from a high-fat diet (HFD) and pancreatic β-cell dysfunction from streptozotocin (STZ) to produce hyperglycaemia, peripheral insulin resistance, hyperlipidaemia and elevated fat mass to mimic the clinical features of T2D. Ex vivo cardiac function was assessed using Langendorff perfusion with systolic and diastolic contractile depression observed in T2D hearts. Cohorts representing untreated, individual HFD- or STZ-treatments and the combined HFD+STZ approach were used to generate ventricular samples (n=9 per cohort) for sequential and integrated analysis of the proteome, lipidome and metabolome by liquid chromatography-tandem mass spectrometry. This study found that in T2D hearts, HFD treatment primed the metabolome, while STZ treatment was the major driver for changes in the proteome. Both treatments equally impacted the lipidome. Our data suggest that increases in β-oxidation and early TCA cycle intermediates promoted rerouting via 2-oxaloacetate to glutamate, γ aminobutyric acid and glutathione. Furthermore, we suggest that the T2D heart activates networks to redistribute excess acetyl-CoA towards ketogenesis and incomplete β-oxidation through the formation of short-chain acylcarnitine species. Multi-omics provided a global and comprehensive molecular view of the diabetic heart, which distributes substrates and products from excess β-oxidation, reduces metabolic flexibility and impairs capacity to restore high energy reservoirs needed to respond to and prevent subsequent acute cardiovascular events.

Project description:Obesity and diabetes associated visual impairment and vascular dysfunctions are increasing reasons for vision loss. The detailed mechanisms in these diseases are still largely unknown, but mice models have been useful to study these mechanisms and explore the detailed effects of potential compounds. Such compounds usually have antioxidant and anti-inflammatory properties. These properties are found in anthocyanins and a major source of dietary anthocyanins in Nordic diet is bilberries (European wild blueberries, Vaccinium myrtillus). In this explorative study we show results with differentially expressed genes in retina using a high-fat diet (HFD) mouse model. Our findings displayed differential regulation of genes in pathways for apoptosis, inflammation and oxidative stress, especially systemic lupus erythematosus (SLE), mitogen activated protein kinase (MAPK) and glutathione metabolism. Mice fed with HFD had increased retinal gene expression of several crystallins, which was reduced in the retina of mice fed with bilberries. Bilberries seem to reduce the expression of genes in MAPK and to increase the expression of genes in glutathione metabolism pathway. All together despite minor effects in the mouse phenotype, a diet rich in bilberries may prevent the retinal gene expression changes in the early stages of obesity. Mice were fed ad libitum with normal control diet (NCD, 10% kcal fat), high-fat diet (HFD, 45% kcal fat), 5% (w/w) freeze-dried biberries (Vaccinium myrtillus) in NCD (NCD+BB) or HFD (HFD+BB) for 12 weeks. Diets were prepared in Research Diets Inc. Feed consumption and weight gain were measured during the feeding trial, and blood pressure and serum markers of obesity at the end. Retinas were collected and RNA extracted from all 24 mice samples, and pooled retinas from 4 mice per group were hybridized with standard Illumina protocols. The expression in retinas was analyzed using R, Pathvisio and DAVID to screen for differences between high-fat and berry induced changes to control diets and further bilberry induced changes to HFD up- or downregulated transcripts. diet: NCD, HFD, NCD+BB, HFD+BB

Dataset Information

Dehydrozingerone ameliorate renal structures compromised in diabetic nephropathy

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets