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Isolated dyslipidemia triggers early kidney injury through fibrotic remodeling, subcellular lipid accumulation, and AMPK overexpression

Ousmaal, Mohamed El Fadel ; Gaceb, Abderahim LU ; Benali, Anissa and Giaimis, Jean (2025) In Ultrastructural Pathology 49(6). p.537-549
Abstract

Dyslipidemia is increasingly recognized as a potential driver of chronic kidney disease, independent of other components of the metabolic syndrome. This study aimed to investigate the direct impact of isolated dyslipidemia on kidney structure and function in dyslipidemic Psammomys obesus (P. obesus). P. obesus animals were fed either a low-energy diet (LED) or high-energy diet (HED) for 12 weeks. Renal tissues were analyzed for fibrosis, inflammation and lipid droplet accumulation, using Masson’s trichrome staining and reticulin fiber staining. Protein expression of AMPK, eNOS, and TGF-β was assessed by Western blot and densitometry analysis. The HED exerted a distinctly pronounced hyperlipidemic effect, as evidenced by increased levels... (More)

Dyslipidemia is increasingly recognized as a potential driver of chronic kidney disease, independent of other components of the metabolic syndrome. This study aimed to investigate the direct impact of isolated dyslipidemia on kidney structure and function in dyslipidemic Psammomys obesus (P. obesus). P. obesus animals were fed either a low-energy diet (LED) or high-energy diet (HED) for 12 weeks. Renal tissues were analyzed for fibrosis, inflammation and lipid droplet accumulation, using Masson’s trichrome staining and reticulin fiber staining. Protein expression of AMPK, eNOS, and TGF-β was assessed by Western blot and densitometry analysis. The HED exerted a distinctly pronounced hyperlipidemic effect, as evidenced by increased levels of total cholesterol, LDL-C, and triglycerides, without affecting glycemia. Animals fed a HED showed significant perivascular and interstitial fibrosis, tubular atrophy, tubular necrosis, and inflammation. Lipid droplets were notably observed within podocytes in the glomeruli of dyslipidemic animals. Western blot analysis revealed increased AMPK expression and TGF-β, along with altered levels of eNOS, indicating activation of metabolic stress and fibrotic pathways in HED group. Dyslipidemic P. obesus display significant kidney injury marked by lipid accumulation in podocytes, AMPK overexpression, and progressive fibrosis. These results highlight the direct renal impact of dyslipidemia in the absence of other metabolic stressors.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AMPK, dyslipidemia, high-energy diet, kidney, Psammomys obesus
in
Ultrastructural Pathology
volume
49
issue
6
pages
13 pages
publisher
Taylor & Francis
external identifiers
  • scopus:105019185379
  • pmid:41102006
ISSN
0191-3123
DOI
10.1080/01913123.2025.2575988
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 Taylor & Francis Group, LLC.
id
a58775ee-690c-4290-9ac2-b18a4b7fa727
date added to LUP
2026-01-19 15:08:52
date last changed
2026-01-19 15:09:01
@article{a58775ee-690c-4290-9ac2-b18a4b7fa727,
  abstract     = {{<p>Dyslipidemia is increasingly recognized as a potential driver of chronic kidney disease, independent of other components of the metabolic syndrome. This study aimed to investigate the direct impact of isolated dyslipidemia on kidney structure and function in dyslipidemic Psammomys obesus (P. obesus). P. obesus animals were fed either a low-energy diet (LED) or high-energy diet (HED) for 12 weeks. Renal tissues were analyzed for fibrosis, inflammation and lipid droplet accumulation, using Masson’s trichrome staining and reticulin fiber staining. Protein expression of AMPK, eNOS, and TGF-β was assessed by Western blot and densitometry analysis. The HED exerted a distinctly pronounced hyperlipidemic effect, as evidenced by increased levels of total cholesterol, LDL-C, and triglycerides, without affecting glycemia. Animals fed a HED showed significant perivascular and interstitial fibrosis, tubular atrophy, tubular necrosis, and inflammation. Lipid droplets were notably observed within podocytes in the glomeruli of dyslipidemic animals. Western blot analysis revealed increased AMPK expression and TGF-β, along with altered levels of eNOS, indicating activation of metabolic stress and fibrotic pathways in HED group. Dyslipidemic P. obesus display significant kidney injury marked by lipid accumulation in podocytes, AMPK overexpression, and progressive fibrosis. These results highlight the direct renal impact of dyslipidemia in the absence of other metabolic stressors.</p>}},
  author       = {{Ousmaal, Mohamed El Fadel and Gaceb, Abderahim and Benali, Anissa and Giaimis, Jean}},
  issn         = {{0191-3123}},
  keywords     = {{AMPK; dyslipidemia; high-energy diet; kidney; Psammomys obesus}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{537--549}},
  publisher    = {{Taylor & Francis}},
  series       = {{Ultrastructural Pathology}},
  title        = {{Isolated dyslipidemia triggers early kidney injury through fibrotic remodeling, subcellular lipid accumulation, and AMPK overexpression}},
  url          = {{http://dx.doi.org/10.1080/01913123.2025.2575988}},
  doi          = {{10.1080/01913123.2025.2575988}},
  volume       = {{49}},
  year         = {{2025}},
}