Evidence map›Paper›PMID 33968771›Full record

ArticleFrontiers in oncology2021

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells.

Jonathan Tucci, Ting Chen, Katherine Margulis, Etan Orgel, Rebecca L Paszkiewicz, Michael D Cohen, Matthew J Oberley, Rachel Wahhab, Anthony E Jones, Ajit S Divakaruni and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
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

38 citing papers in PubMed, 56 citations in OpenAlex.

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  5. Implications of adipocyte dysfunction in pediatric obesity: a narrative review.Pediatric endocrinology, diabetes, and metabolism · 2026
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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

15 authors at 4 institutions in 3 countries.

Jonathan TucciDiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Ting ChenDivision of Pediatric Endocrinology, University of California Los Angeles (UCLA) Children's Discovery and Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, United States.
Katherine MargulisDepartment of Chemistry, Stanford University, Stanford, CA, United States.
Etan OrgelCancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Rebecca L PaszkiewiczDivision of Pediatric Endocrinology, University of California Los Angeles (UCLA) Children's Discovery and Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, United States.
Michael D CohenDivision of Pediatric Endocrinology, University of California Los Angeles (UCLA) Children's Discovery and Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, United States.
Matthew J OberleyDepartment of Pathology, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Rachel WahhabDiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Anthony E JonesDepartment of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, CA, United States.
Ajit S DivakaruniDepartment of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, CA, United States.
Cheng-Chih HsuDepartment of Chemistry, Stanford University, Stanford, CA, United States.
Sarah E NollDepartment of Chemistry, Stanford University, Stanford, CA, United States.
Xia ShengDiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Richard N ZareDepartment of Chemistry, Stanford University, Stanford, CA, United States.
Steven D MittelmanDiabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, CA, United States.
Children's Hospital of Los Angeles · USStanford University · USMattel Children's Hospital · USUniversity of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
Understanding How Metabolic Cofactors Control Cell Function and FateR35GM138003 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Ajit Divakaruni · 2020 to 2026
$2.8M
Adipocytes are Important Players in the Acute Lymphoblastic Leukemia MicroenvironmentR01CA201444 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MITTELMAN, STEVEN DAVID · 2016 to 2020
$1.9M
NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA201444NCI NIH HHS T32 CA009056NIGMS NIH HHS R35 GM138003
6 · The paper itself

Abstract

backgroundThere is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells.

methodsWe cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes.

resultsAdipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells.

conclusionThese findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome.

Indexed as

adipocytesFFAleukemialipid dropletsmicroenvironment

Identifiers

PMID33968771
PMCPMC8100891
OpenAlexW3163468806

What OpenQuestion 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 OpenQuestion graph.