Dataset Information

Mouse Kidney MS - Standas diet WT/ High fat diet WT/ Standard diet ANT2 KO/ High fat diet ANT2 KO

ABSTRACT: Impairments in ATP production and transport in renal proximal tubule cells (RPTCs) result in obesity-induced chronic kidney disease (CKD), manifested by kidney dysfunction, inflammation, adiposity, and fibrosis. Here we assessed the role of adenine nucleotide transporter 2 (ANT2), the main regulator of cellular ATP content in RPTCs, in the development of obesity-induced CKD and its metabolic abnormalities. Obese RPTC-ANT2-/- mice exhibited normal renal morphology, function, and lack of kidney adiposity and fibrosis as well as an improvement in whole-body energy metabolism, manifested by normal glucose and lipid homeostasis and reduced hepatic steatosis. ANT2-depleted RPTCs rewired their primary metabolic program from oxidizing fatty acids as a primary energy source toward aerobic glycolysis, mediated via the testis-selective ANT4. We propose that RPTC-ANT2 plays an important role in the development of obesity-induced CKD, and that its nullification triggers mitochondrial protection, RPTC cellular survival, kidney preservation, and improvements in systemic metabolism.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

SUBMITTER: Anna Permyakova

LAB HEAD: Joseph Tam

PROVIDER: PXD042128 | Pride | 2025-05-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Experimental_design.csv	Csv
	Seq68486_HFX-SH113-Kid.raw	Raw
	Seq68486_HFX_b-SH113_kid.raw	Raw
	Seq68654_HFX-SH115_kid.raw	Raw
	Seq68655_HFX-SH116-kid.raw	Raw

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Publications

Renal Mitochondrial ATP Transporter Ablation Ameliorates Obesity-Induced CKD.

Permyakova Anna A Hamad Sharleen S Hinden Liad L Baraghithy Saja S Kogot-Levin Aviram A Yosef Omri O Shalev Ori O Tripathi Manish Kumar MK Amal Haitham H Basu Abhishek A Arif Muhammad M Cinar Resat R Kunos George G Berger Michael M Leibowitz Gil G Tam Joseph J

Journal of the American Society of Nephrology : JASN 20240111 3

<h4>Significance statement</h4>This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in the pathogenesis of obesity-induced CKD. Our data demonstrate that ANT2 depletion in renal proximal tubule cells (RPTCs) leads to a shift in their primary metabolic program from fatty acid oxidation to aerobic glycolysis, resulting in mitochondrial protection, cellular survival, and preservation of renal function. These findings provide new insights into the underlying mechanis ...[more]

PMID: 38200648

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