ArticleCell metabolism2023
FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.
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Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 31 citations in OpenAlex.
- Double-bond geometry determines fatty acid metabolic fate and ferroptosis sensitivity.bioRxiv : the preprint server for biology · 2026Article
- New Analytical Technologies to Resolve, Interpret, and Understand Lipid Complexity.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Fatty Acids as Prebiotics and Their Role in Antibiofilm Activity.Antibiotics (Basel, Switzerland) · 2026Review
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- The Central Role of Lipid Metabolism Disorders in Diabetes Mellitus: Mechanisms, Clinical Manifestations, and Emerging Therapeutic Strategies.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Staphylococcus aureus fatty acid metabolism governs saeRS-mediated aggregation in joint infections.Nature communications · 2025Article
- Androgen Receptors Promote Oxidative Phosphorylation and Resistance to Palmitate Lipotoxicity in ER-Mutant Breast Cancer.Endocrinology · 2025Article
- Fatty acid binding protein 1 (FABP1) depletion promotes an oxidative metabolic shift in Caco-2 colorectal cancer cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.Science advances · 2025Article
- The Advanced Glycation End-Products (AGE)-Receptor for AGE System (RAGE): An Inflammatory Pathway Linking Obesity and Cardiovascular Diseases.International journal of molecular sciences · 2025Review
- Article
- Lipotoxicity Induces β-cell Small Extracellular Vesicle-Mediated β-cell Dysfunction in Male Mice.Endocrinology · 2025Article
- Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation.Molecular metabolism · 2025Article
- A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.Experimental & molecular medicine · 2024Article
- Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.Communications biology · 2024Article
- Metabolic ripple effects - deciphering how lipid metabolism in cancer interfaces with the tumor microenvironment.Disease models & mechanisms · 2024Review
- The key role of altered tubule cell lipid metabolism in kidney disease development.Kidney international · 2024Review
- Lipid droplets and fatty acid-induced lipotoxicity: in a nutshell.FEBS letters · 2024Article
- Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024Review
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Authors and funding
38 authors at 4 institutions in 4 countries.
Nicolas WiederBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurology with Experimental Neurology and Berlin Institute of Health, Charité, 10117 Berlin, Germany.
Juliana Coraor FriedBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Choah KimBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Eriene-Heidi SidhomBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Matthew R BrownBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jamie L MarshallBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Carlos ArevaloBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Moran Dvela-LevittBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Maria Kost-AlimovaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jonas SieberDepartment of Endocrinology, Metabolism and Cardiovascular Systems, University of Fribourg, Fribourg, Switzerland.
Katlyn R GabrielBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Julian PachecoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Clary ClishBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hamdah Shafqat AbbasiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Shantanu SinghBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Justine C RutterBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
Martine TherrienBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Haejin YoonDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center for Cancer Research at Harvard, Boston, MA 02115, 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 02115, USA.
Ranjan DevkotaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jonnell SmallBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Vedagopuram SreekanthBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Divisions of Renal Medicine and Engineering, Brigham and Women's Hospital, Boston, MA 02115, USA.
Myeonghoon HanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Donghyun LimBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anne E CarpenterBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jason FlannickBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA.
Hilary FinucaneBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Mass General Hospital, Boston, MA 02114, USA.
Marcia C HaigisBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center for Cancer Research at Harvard, Boston, MA 02115, USA.
Melina ClaussnitzerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Metabolism Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Eric SheuLaboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Beth StevensBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
Bridget K WagnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Amit ChoudharyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Divisions of Renal Medicine and Engineering, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jillian L ShawBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Juan Lorenzo PabloBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anna GrekaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: agreka@bwh.harvard.edu.
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
$50.0MROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MARTIN TORRIANI · 1994 to 2026
$31.6MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MBridging 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
$9.5MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4MExtracting rich information from biological imagesR35GM122547 · NIGMS · BROAD INSTITUTE, INC. · PI Anne E. Carpenter · 2017 to 2026
$6.2MMolecular mechanisms of podocyte injury in FSGSR01DK095045 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Anna Greka, Juan Lorenzo Pablo · 2014 to 2026
$5.1MRole of TRPC5 channel inhibition in the treatment of glomerular diseaseR01DK099465 · NIDDK · BROAD INSTITUTE, INC. · PI Anna Greka · 2014 to 2026
$5.1MMetaboregulatory microbial pathways shifted after bariatric surgeryR01DK126855 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Eric Garland Sheu · 2021 to 2026
$4.2MIn vivo and in vitro rare coding variant analyses to identify modulations of the adipocyte differentiation pathway that affect T2D riskR01DK125490 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Jason Flannick · 2020 to 2026
$3.9MOpera Phenix high-throughput microplate confocal imager for high-content screeningS10OD026839 · OD · BROAD INSTITUTE, INC. · PI WAGNER, BRIDGET K · 2019 to 2019
$1.0MNBCe1-mediated Regulation of HCO3- is a Novel Mechanism Underlying Metabolic Reprogramming and CystogenesisK00DK123834 · NIDDK · BROAD INSTITUTE, INC. · PI BROWN, MATTHEW · 2022 to 2025
$369kNICHD NIH HHS P50 HD105351NIDDK NIH HHS F30 DK112477NIDDK NIH HHS F31 DK126252NIDDK NIH HHS K00 DK123834NIDDK NIH HHS P30 DK040561NIDDK NIH HHS R01 DK095045NIDDK NIH HHS R01 DK099465NIDDK NIH HHS R01 DK125490NIDDK NIH HHS R01 DK126855NIDDK NIH HHS UM1 DK126185NIGMS NIH HHS R35 GM122547NIGMS NIH HHS T32 GM007216NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273NIH HHS S10 OD026839
Abstract
Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. 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.
Indexed as
Diabetes Mellitus, Type 2Fatty Acids, NonesterifiedBiologyFatty AcidsHumansSignal TransductionFatty AcidsFatty Acids, NonesterifiedCMIPerucic acidGWASkidneylipidomicsmicrogliaobesitypancreatic β celltranscriptomicstype 2 diabetes
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