Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice.

Nguyen, LT; Larkin, BP; Wang, R; Faiz, A; Pollock, CA; Saad, S

Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice.

Nguyen, LT Larkin, BP Wang, R Faiz, A

Pollock, CA Saad, S

Permalink

Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Nutrients, 2022, 14, (4), pp. 1-13
Issue Date:: 2022-02-13

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (4.32 MB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Nguyen, LT
dc.contributor.author	Larkin, BP
dc.contributor.author	Wang, R
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Pollock, CA
dc.contributor.author	Saad, S
dc.date.accessioned	2022-12-14T04:41:49Z
dc.date.available	2022-02-09
dc.date.available	2022-12-14T04:41:49Z
dc.date.issued	2022-02-13
dc.identifier.citation	Nutrients, 2022, 14, (4), pp. 1-13
dc.identifier.issn	2072-6643
dc.identifier.issn	2072-6643
dc.identifier.uri	http://hdl.handle.net/10453/164405
dc.description.abstract	Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild-moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease's prognostication.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Nutrients
dc.relation.isbasedon	10.3390/nu14040785
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0908 Food Sciences, 1111 Nutrition and Dietetics
dc.subject.mesh	Animals
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Diabetic Nephropathies
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Disease Progression
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Kidney
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Animals
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Diabetic Nephropathies
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Disease Progression
dc.subject.mesh	Kidney
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Kidney
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice
dc.subject.mesh	Diabetic Nephropathies
dc.subject.mesh	Diabetes Mellitus, Type 2
dc.subject.mesh	Disease Progression
dc.subject.mesh	DNA Methylation
dc.subject.mesh	Diet, High-Fat
dc.title	Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	Switzerland
utslib.for	0908 Food Sciences
utslib.for	1111 Nutrition and Dietetics
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-14T04:41:32Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	14
utslib.citation.issue	4

Abstract:

Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild-moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease's prognostication.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/164405