Evidence map›Paper›PMID 40875392›Full record

ArticleAmerican journal of physiology. Renal physiology2025

Fatty acids and albumin are transported by distinct mechanisms in the proximal tubule.

Nestor H Garcia, Robert J Gaivin, Shenaz Khan, Vincent Li, Youssef Rbaibi, Ora A Weisz, Jeffrey L Garvin, Jeffrey R Schelling

Abstract read
In one paragraph

Article in American journal of physiology. Renal physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

8 authors.

Nestor H GarciaDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.ORCID 0000-0002-9057-9030
Robert J GaivinDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.ORCID 0009-0002-3000-0661
Shenaz KhanDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.
Vincent LiDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.
Youssef RbaibiDivision of Renal-Electrolyte, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Ora A WeiszDivision of Renal-Electrolyte, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.ORCID 0000-0003-2985-4870
Jeffrey L GarvinDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.ORCID 0000-0002-8647-3815
Jeffrey R SchellingDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, United States.ORCID 0000-0003-3503-2208

Funding

Mechanisms of tubular atrophy in renal diseaseR01DK067528 · NIDDK · CASE WESTERN RESERVE UNIVERSITY · PI SCHELLING, JEFFREY R · 2005 to 2025
$7.1M
Resource Development CoreU54DK137329 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas R Kleyman · 2023 to 2026
$4.8M
The Role of The Proximal Nephron In Salt-Sensitive HypertensionR01HL128053 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI GARVIN, JEFFREY L. · 2016 to 2024
$4.3M
Endocytic Pathway Dysfunction in Dent DiseaseR01DK125049 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WEISZ, ORA A · 2020 to 2024
$2.3M
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 2R01DK067528HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5R01HL128053NHLBI NIH HHS R01 HL128053NIDDK NIH HHS R01 DK067528NIDDK NIH HHS R01 DK125049NIDDK NIH HHS U54 DK137329
6 · The paper itself

Abstract

Under physiologic conditions, proximal tubules depend on basolateral fatty acid (FA) uptake for metabolism. In pathophysiologic conditions due to glomerular filtration barrier disruption, albumin-bound FA undergoes filtration and proximal tubule reabsorption, which leads to lipotoxicity and tubular atrophy. Apical proximal tubule albumin uptake is accomplished by the megalin/cubilin complex and receptor-mediated endocytosis, whereas apical proximal tubule FA uptake is primarily mediated by apical fatty acid transport protein-2 (FATP2). However, a commonly proposed (but untested) alternative model is that the intact albumin-FA complex is cotransported by megalin/cubilin-mediated endocytosis, similar to apolipoproteins. Microperfused mouse proximal tubules demonstrated divergent one- versus two-phase albumin and FA uptake kinetics, with significantly faster albumin compared with FA uptake. LLC-PK1, human proximal tubule cells (HPCT), and opossum kidney (OK) proximal tubule cell lines all expressed megalin, cubilin, and FATP2 mRNA, though in varying amounts. LLC-PK1 cells showed similar one-phase kinetics of dual fluorescently labeled albumin and FA uptake, whereas HPCT cells demonstrated one-phase albumin and two-phase FA uptake kinetics, with significantly faster albumin compared with FA uptake (similar to perfused proximal tubules). FATP2 inhibition blocked FA uptake, but had no effect on albumin uptake in LLC-PK1 and HPCT cells. Megalin and cubilin deletion in OK cells inhibited albumin uptake, but had no effect on FA uptake. We conclude that apical proximal tubule albumin and FA are transported by distinct mechanisms, implying that FAs dissociate from albumin within the proximal tubule lumen before uptake.

Indexed as

AlbuminsFatty AcidsKidney Tubules, ProximalSerum AlbuminAnimalsBiological TransportEndocytosisFatty Acid Transport ProteinsHumansLLC-PK1 CellsLow Density Lipoprotein Receptor-Related Protein-2MiceMice, Inbred C57BLOpossumsReceptors, Cell SurfaceRenal ReabsorptionAlbuminsFatty AcidsFatty Acid Transport Proteinsintrinsic factor-cobalamin receptorLow Density Lipoprotein Receptor-Related Protein-2Lrp2 protein, mouseReceptors, Cell SurfaceSerum Albumincubilinfatty acid transport protein-2fluorescencekineticsmegalin

Identifiers

PMID40875392
PMCPMC12486159

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.