Evidence map›Paper›PMID 40072078›Full record

ArticleCells2025

Caki-1 Spheroids as a Renal Model for Studying Free Fatty Acid-Induced Lipotoxicity.

Dana Battle, Xiangzhe Qiu, Marilyn Alex, London Rivers, Jamie A G Hamilton, Shuichi Takayama, Xueying Zhao

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Dana BattleDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.ORCID 0009-0001-6311-7850
Xiangzhe QiuDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Marilyn AlexDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.ORCID 0009-0005-9669-0791
London RiversDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Jamie A G HamiltonWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.ORCID 0000-0003-3071-6029
Shuichi TakayamaWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA 30332, USA.ORCID 0000-0002-4385-9080
Xueying ZhaoDepartment of Physiology, Morehouse School of Medicine, Atlanta, GA 30310, USA.ORCID 0000-0003-0857-2823

Funding

Training the Trainers: Building Institutional Data Science Capacity to Support Health Disparities ResearchU54MD007602 · NIMHD · MOREHOUSE SCHOOL OF MEDICINE · PI Lilly Hsi-Chih Immergluck · 2018 to 2026
$47.6M
Atlanta Network for Training In KUH Scientific Research (ATLANTIS)TL1DK136047 · NIDDK · EMORY UNIVERSITY · PI Vivien Andrea Sheehan · 2022 to 2026
$3.0M
Molecular mechanisms underlying renal lipotoxicity and DKD progressionR16GM149499 · NIGMS · MOREHOUSE SCHOOL OF MEDICINE · PI Xueying Zhao · 2023 to 2026
$568k
National Institute of Health R16GM149499, TL1DK136047, U54MD007602NIDDK NIH HHS TL1 DK136047NIGMS NIH HHS R16 GM149499NIMHD NIH HHS U54 MD007602
6 · The paper itself

Abstract

Lipotoxicity, resulting from the buildup of excess lipids in non-adipose tissues, is increasingly recognized as a major contributor to the progression of kidney disease, highlighting the need for alternative models to assess its effects on renal cells. The main aim of this study was to investigate the usefulness of Caki-1, a human proximal tubule (PT) and renal cell carcinoma (RCC) representative cell line, as a 3D model system for studying free fatty acid-induced PT lipotoxicity. Caki-1 spheroids were generated and maintained on ultra-low attachment plates and characterized regarding time-dependent morphology changes. In optimal 3D culture conditions, Caki-1 cells formed well-defined large compact spheroids with uniform morphology, good circularity, and increased diameter from days 4-12. Chronic exposure to saturated palmitate resulted in dose- and time-dependent spheroid disintegration and cell death, including dispersed and flattened spheroid morphology, with increased dead cells in the peripheral layers and decreased spheroid core. Moreover, palmitate-treated spheroids showed a significant increase in cleaved poly(ADP-ribose) polymerase (PARP) and active caspase-3. Palmitate-induced PARP cleavage, as well as endoplasmic reticulum (ER) stress and autophagy dysfunction, were blunted by triacsin C, an inhibitor of long-chain acyl-CoA synthetases. In addition, co-incubation with unsaturated oleate prevented palmitate-induced spheroid disintegration and apoptotic cell death in Caki-1 3D culture. While fatty acid overload upregulated lipid droplet protein perilipin 2 in Caki-1 cells, knockdown of perilipin 2 by siRNAs resulted in an exacerbation of palmitate-induced cell death. Together, these results indicate that the 3D Caki-1 spheroid model is a simple and reproducible in vitro system for studying renal lipotoxicity and lipid metabolism that gives useful readouts at the molecular, cellular, and multicellular levels.

Indexed as

Fatty Acids, NonesterifiedKidneyKidney Tubules, ProximalModels, BiologicalSpheroids, CellularApoptosisAutophagyCarcinoma, Renal CellCell Line, TumorEndoplasmic Reticulum StressHumansPalmitatesPerilipin-2Fatty Acids, NonesterifiedPalmitatesPerilipin-2autophagyER stresslipid dropletlipotoxicitytubular epithelial cells

Identifiers

PMID40072078
PMCPMC11899473

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.