Evidence map›Paper›PMID 36865221›Full record

ArticlebioRxiv : the preprint server for biology2023

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.

Nicolas Wieder, Juliana Coraor Fried, Choah Kim, Eriene-Heidi Sidhom, Matthew R Brown, Jamie L Marshall, Carlos Arevalo, Moran Dvela-Levitt, Maria Kost-Alimova, Jonas Sieber and 28 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors at 4 institutions in 4 countries.

Nicolas WiederBroad Institute of MIT and Harvard, Cambridge, USA.
Juliana Coraor FriedBroad Institute of MIT and Harvard, Cambridge, USA.
Choah KimBroad Institute of MIT and Harvard, Cambridge, USA.
Eriene-Heidi SidhomBroad Institute of MIT and Harvard, Cambridge, USA.
Matthew R BrownBroad Institute of MIT and Harvard, Cambridge, USA.
Jamie L MarshallBroad Institute of MIT and Harvard, Cambridge, USA.
Carlos ArevaloBroad Institute of MIT and Harvard, Cambridge, USA.
Moran Dvela-LevittBroad Institute of MIT and Harvard, Cambridge, USA.
Maria Kost-AlimovaBroad Institute of MIT and Harvard, Cambridge, USA.
Jonas SieberDepartment of Endocrinology, Metabolism and Cardiovascular Systems, University of Fribourg, Fribourg, Switzerland.
Katlyn R GabrielBroad Institute of MIT and Harvard, Cambridge, USA.
Julian PachecoBroad Institute of MIT and Harvard, Cambridge, USA.
Clary ClishBroad Institute of MIT and Harvard, Cambridge, USA.
Hamdah Shafqat AbbasiBroad Institute of MIT and Harvard, Cambridge, USA.
Shantanu SinghBroad Institute of MIT and Harvard, Cambridge, USA.
Justine RutterBroad Institute of MIT and Harvard, Cambridge, USA.
Martine TherrienBroad Institute of MIT and Harvard, Cambridge, USA.
Haejin YoonDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Zon Weng LaiHarvard Chan Advanced Multiomics Platform, Harvard T.H. Chan School of Public Health, Boston MA 02115 USA.
Aaron BaublisHarvard Chan Advanced Multiomics Platform, Harvard T.H. Chan School of Public Health, Boston MA 02115 USA.
Renuka SubramanianLaboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Ranjan DevkotaBroad Institute of MIT and Harvard, Cambridge, USA.
Jonnell SmallBroad Institute of MIT and Harvard, Cambridge, USA.
Vedagopuram SreekanthBroad Institute of MIT and Harvard, Cambridge, USA.
Myeonghoon HanBroad Institute of MIT and Harvard, Cambridge, USA.
Donghyun LimBroad Institute of MIT and Harvard, Cambridge, USA.
Anne E CarpenterBroad Institute of MIT and Harvard, Cambridge, USA.
Jason FlannickBroad Institute of MIT and Harvard, Cambridge, USA.
Hilary FinucaneBroad Institute of MIT and Harvard, Cambridge, USA.
Marcia C HaigisBroad Institute of MIT and Harvard, Cambridge, USA.
Melina ClaussnitzerBroad Institute of MIT and Harvard, Cambridge, USA.
Eric SheuLaboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Beth StevensBroad Institute of MIT and Harvard, Cambridge, USA.
Bridget K WagnerBroad Institute of MIT and Harvard, Cambridge, USA.
Amit ChoudharyBroad Institute of MIT and Harvard, Cambridge, USA.
Jillian L ShawBroad Institute of MIT and Harvard, Cambridge, USA.
Juan Lorenzo PabloBroad Institute of MIT and Harvard, Cambridge, USA.
Anna GrekaBroad Institute of MIT and Harvard, Cambridge, USA.
Broad Institute · USHarvard University · USBrigham and Women's Hospital · USUniversity of Fribourg · CH

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Bridging the gap between type 2 diabetes GWAS and therapeutic targetsUM1DK126185 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CLAUSSNITZER, MELINA C, GLOYN, ANNA LOUISE · 2020 to 2024
$9.5M
Extracting rich information from biological imagesR35GM122547 · NIGMS · BROAD INSTITUTE, INC. · PI Anne E. Carpenter · 2017 to 2026
$6.2M
Molecular mechanisms of podocyte injury in FSGSR01DK095045 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Anna Greka, Juan Lorenzo Pablo · 2014 to 2026
$5.1M
Role of TRPC5 channel inhibition in the treatment of glomerular diseaseR01DK099465 · NIDDK · BROAD INSTITUTE, INC. · PI Anna Greka · 2014 to 2026
$5.1M
Metaboregulatory microbial pathways shifted after bariatric surgeryR01DK126855 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Eric Garland Sheu · 2021 to 2026
$4.2M
NBCe1-mediated Regulation of HCO3- is a Novel Mechanism Underlying Metabolic Reprogramming and CystogenesisK00DK123834 · NIDDK · BROAD INSTITUTE, INC. · PI BROWN, MATTHEW · 2022 to 2025
$369k
Effect of mitochondrial mutations on ion channel activity and cytoskeletal homeostasisF30DK112477 · NIDDK · HARVARD MEDICAL SCHOOL · PI SIDHOM, ERIENE-HEIDI I · 2017 to 2020
$170k
Dissecting the molecular mechanisms underlying lipotoxicity in the kidney.F31DK126252 · NIDDK · HARVARD MEDICAL SCHOOL · PI KIM, CHOAH · 2020 to 2022
$99k
NIDDK NIH HHS F30 DK112477NIDDK NIH HHS F31 DK126252NIDDK NIH HHS K00 DK123834NIDDK NIH HHS R01 DK095045NIDDK NIH HHS R01 DK099465NIDDK NIH HHS R01 DK126855NIDDK NIH HHS UM1 DK126185NIGMS NIH HHS R35 GM122547NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Cellular exposure to free fatty acids (FFA) is implicated in the pathogenesis of obesity-associated diseases. However, studies to date have assumed that a few select FFAs are representative of broad structural categories, and there are no scalable approaches to comprehensively assess the biological processes induced by exposure to diverse FFAs circulating in human plasma. Furthermore, assessing how these FFA- mediated processes interact with genetic risk for disease remains elusive. Here we report the design and implementation of FALCON (Fatty Acid Library for Comprehensive ONtologies) as an unbiased, scalable and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids (MUFAs) with a distinct lipidomic profile associated with decreased membrane fluidity. Furthermore, we developed a new approach to prioritize genes that reflect the combined effects of exposure to harmful FFAs and genetic risk for type 2 diabetes (T2D). Importantly, we found that c-MAF inducing protein (CMIP) protects cells from exposure to FFAs by modulating Akt signaling and we validated the role of CMIP in human pancreatic beta cells. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism. Highlights: FALCON (Fatty Acid Library for Comprehensive ONtologies) enables multimodal profiling of 61 free fatty acids (FFAs) to reveal 5 FFA clusters with distinct biological effectsFALCON is applicable to many and diverse cell typesA subset of monounsaturated FAs (MUFAs) equally or more toxic than canonical lipotoxic saturated FAs (SFAs) leads to decreased membrane fluidityNew approach prioritizes genes that represent the combined effects of environmental (FFA) exposure and genetic risk for diseaseC-Maf inducing protein (CMIP) is identified as a suppressor of FFA-induced lipotoxicity via Akt-mediated signaling.

Identifiers

PMID36865221
PMCPMC9979987
OpenAlexW4321457450

What Socratic 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 Socratic graph.