ArticleScience (New York, N.Y.)2019
Targeting a ceramide double bond improves insulin resistance and hepatic steatosis.
Open access · greenAbstract read
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Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 291 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
291citing papers in PubMed, 1 pooled it
19.8field-weighted citation impact, top 1% of its field
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Who cites it
291 citing papers in PubMed, 1 synthesis or guideline pooled it, 437 citations in OpenAlex.
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- An extra virgin olive oil-enriched chocolate spread positively modulates insulin-resistance markers compared with a palm oil-enriched one in healthy young adults: A double-blind, cross-over, randomised controlled trial.Diabetes/metabolism research and reviews · 2022Trial
- Excessive EFHD1-dependent ER-mitochondrial contacts drive a maladaptive antiviral response in metabolic liver disease.The Journal of clinical investigation · 2026Article
- Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Immunometabolism in Obesity-Associated Type 2 Diabetes: Molecular Mechanisms and Emerging Therapeutic Targets.International journal of molecular sciences · 2026Review
- Arsenic exposure, arsenic metabolism, and plasma lipidome in relation to type 2 diabetes and glycemic traits: a lipidome-wide association study.Journal of advanced research · 2026Article
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Targeting circulating fatty acid-binding protein 4 ameliorates obesity-associated hepatic steatosis.JHEP reports : innovation in hepatology · 2026Article
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Sphingolipid homeostasis and dysregulation in liver function and disease.Life metabolism · 2026Review
- A gut microbiome-lipid axis in early pregnancy is associated with metabolic dysregulation and diabetes risk.iMeta · 2026Article
- N6-(2-Hydroxyethyl) Adenosine Alleviates Hepatic Steatosis and Insulin Resistance by Inhibiting JunB+ Adipocytes.Phytotherapy research : PTR · 2026Article
- Diet-Induced Ceramide Remodeling as a Mechanistic Link to Cardiac Metabolic Dysfunction.Nutrients · 2026Review
- Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038.International journal of molecular sciences · 2026Article
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Metabolic Pathways Linking Atherosclerotic Cardiovascular Disease With Metabolic Dysfunction-Associated Steatotic Liver Disease.Current atherosclerosis reports · 2026Review
- Lifespan trajectories of serum sphingolipids in a clinically healthy Swiss population, towards precision medicine in cardiometabolic health assessment.Communications medicine · 2026Article
- Review
- Dapagliflozin induces renal lipidomic remodeling and systemic metabolic improvement.Biology direct · 2026Article
231 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
35 authors at 7 institutions in 4 countries.
Bhagirath ChaurasiaDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-7998-9290
Trevor S TippettsDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-1419-7057
Rafael Mayoral MonibasMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-6645-7172
Jinqi LiuMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-0094-9801
Ying LiDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-6859-7208
Liping WangDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0003-3537-0952
Joseph L WilkersonDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0003-4683-7589
C Rufus SweeneyDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.
Renato Felipe PereiraSchool of Dentistry, São Paulo State University (UNESP), Araçatuba 16015, Brazil.
Doris Hissako SumidaSchool of Dentistry, São Paulo State University (UNESP), Araçatuba 16015, Brazil.ORCID 0000-0003-3753-229X
J Alan MaschekDepartment of Biochemistry and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0003-3217-2299
James E CoxDepartment of Biochemistry and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-5977-2350
Vincent KaddaiDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.
Graeme Iain LancasterBaker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
Monowarul Mobin SiddiqueFaculty of Science, University of Brunei Darussalam, Gadong 1410, Brunei Darussalam.ORCID 0000-0002-1588-9004
Annelise PossDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-4008-9711
Mackenzie PearsonSciex, Framingham, MA 01701, USA.ORCID 0000-0002-8659-0659
Santhosh SatapatiMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-9087-809X
Heather ZhouMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
David G McLarenMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Stephen F PrevisMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Ying ChenMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Ying QianMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0003-2370-3377
Aleksandr PetrovMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Margaret WuMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Xiaolan ShenMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0003-2492-8981
Jun YaoMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-0191-5224
Christian N NunesMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-8295-4910
Andrew D HowardMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Liangsu WangMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Mark D ErionMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.
Jared RutterDepartment of Biochemistry and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.ORCID 0000-0002-2710-9765
William L HollandDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA.
David E KelleyMerck Research Laboratories, Merck, Kenilworth, NJ 07033, USA.ORCID 0000-0002-0143-0956
Scott A SummersDepartment of Nutrition and Integrative Physiology and the Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, UT 84112, USA. scott.a.summers@health.utah.edu.ORCID 0000-0002-4919-0592
Merck & Co., Inc., Rahway, NJ, USA (United States) · USUniversity of Utah · USUniversidade Estadual Paulista (Unesp) · BRBaker Heart and Diabetes Institute · AUFramingham State University · USHoward Hughes Medical Institute · USUniversiti Brunei Darussalam · BN
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MWU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1MInterdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8MDihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic DiseasesR44DK116450 · NIDDK · POTRERO HILL THERAPEUTICS, INC. · PI BLITZER, JEREMY, SUMMERS, SCOTT A · 2018 to 2022
$4.7MLiver-islet and intra-islet cross talk in alpha cell hyperplasia and beta cell regenerationR01DK112826 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HOLLAND, WILLIAM L · 2017 to 2025
$3.4MThe Role of Ceramides in Skeletal MuscleR01DK115824 · NIDDK · UNIVERSITY OF UTAH · PI SUMMERS, SCOTT A · 2018 to 2021
$2.6MTargeting a Ceramide Double Bond to Treat Cardiometabolic DisordersR01DK122001 · NIDDK · UNIVERSITY OF UTAH · PI SUMMERS, SCOTT A · 2019 to 2022
$1.9MSphingolipid-Mediated Dysregulation of Glucose and Energy Homeostasis in the CNSR01DK108833 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HOLLAND, WILLIAM L · 2016 to 2020
$1.8MThe Native American Short-Term Research Education Program in Children's Health Supplemental Proposal for additional Exceptional Mentoring ExperiencesR25HL108828 · NHLBI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HOLSTI, MAIJA · 2011 to 2025
$1.6MNative American Research Internship (NARI) Summer Program in Diabetes, Obesity and MetabolismR25DK109894 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HOLSTI, MAIJA, SUMMERS, SCOTT A · 2016 to 2025
$1.1MDihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic DiseasesR43DK116450 · NIDDK · POTRERO HILL THERAPEUTICS, INC. · PI BLITZER, JEREMY, SUMMERS, SCOTT A · 2017 to 2017
$225kNCATS NIH HHS UL1 TR001863NHLBI NIH HHS R25 HL108828NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK108833NIDDK NIH HHS R01 DK112826NIDDK NIH HHS R01 DK115824NIDDK NIH HHS R01 DK122001NIDDK NIH HHS R25 DK109894NIDDK NIH HHS R43 DK116450NIDDK NIH HHS R44 DK116450NIDDK NIH HHS T32 DK091317
Abstract
Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.
Indexed as
AnimalsCeramidesDiet, High-FatFatty LiverGene DeletionInsulin ResistanceLeptinMembrane ProteinsMiceMice, Mutant StrainsOxidoreductasesSphingolipidsCeramidesDegs protein, mousedihydroceramideLeptinMembrane ProteinsOxidoreductasesSphingolipids
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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.