Selected Publications

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice

Md Torikul Islam, Jinjin Cai, Shanena Allen, Denisse G Moreno, Samuel I Bloom, R Colton Bramwell, Jonathan Mitton, Andrew G Horn, Weiquan Zhu, Anthony J Donato, William L Holland, Lisa A Lesniewski

Arterioscler Thromb Vasc Biol. 2024 May;44(5):1101-1113. doi: 10.1161/ATVBAHA.123.319375.Epub 2024 Mar 28.

Sphingosine-1-phosphate controls endothelial sphingolipid homeostasis via ORMDL

Linda Sasset, Kamrul H Chowdhury, Onorina L Manzo, Luisa Rubinelli, Csaba Konrad, J Alan Maschek, Giovanni Manfredi, William L Holland, Annarita Di Lorenzo

EMBO Rep. 2023 Jan 9;24(1):e54689. doi: 10.15252/embr.202254689.Epub 2022 Nov 21.

Endothelial specific reduction in Arf6 impairs insulin-stimulated vasodilation and skeletal muscle blood flow resulting in systemic insulin resistance

Md Torikul Islam, Jinjin Cai, Shanena Allen, Denisse G Moreno, Samuel I Bloom, R Colton Bramwell, Jonathan Mitton, Andrew G Horn, Weiquan Zhu, Anthony J Donato, William L Holland, Lisa A Lesniewski

bioRxiv [Preprint]. 2023 May 3:2023.05.02.539173. doi: 10.1101/2023.05.02.539173.

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin

Tara R Price, Donnie S Stapleton, Kathryn L Schueler, Marie K Norris, Brian W Parks, Brian S Yandell, Gary A Churchill, William L Holland, Mark P Keller, Alan D Attie

PLoS Genet. 2023 Jul 31;19(7):e1010713. doi: 10.1371/journal.pgen.1010713.eCollection 2023 Jul.

Germline and conditional ghrelin knockout increases islet size

Sean M Tatum, William L Holland

J Clin Invest. 2023 Dec 15;133(24):e175799.doi: 10.1172/JCI175799.

Hepatic sialic acid synthesis modulates glucose homeostasis in both liver and skeletal muscle

Jun Peng, Liming Yu, Linzhang Huang, Vivian A Paschoal, Haiyan Chu, Camila O de Souza, Joseph V Varre, Da Young Oh, Jennifer J Kohler, Xue Xiao, Lin Xu, William L Holland, Philip W Shaul, Chieko Mineo

Mol Metab. 2023 Dec:78:101812. doi: 10.1016/j.molmet.2023.101812.Epub 2023 Sep 28.

Identification of genetic drivers of plasma lipoprotein size in the Diversity Outbred mouse population

Tara R Price, Christopher H Emfinger, Kathryn L Schueler, Sarah King, Rebekah Nicholson, Tim Beck, Brian S Yandell, Scott A Summers, William L Holland, Ronald M Krauss, Mark P Keller, Alan D Attie

J Lipid Res. 2023 Dec;64(12):100471. doi: 10.1016/j.jlr.2023.100471.Epub 2023 Nov 7.

Phospholipid isotope tracing reveals β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma

Chad VanSant-Webb, Hayden K Low, Junko Kuramoto, Claire E Stanley, Hantao Qiang, Audrey Su, Alexis N Ross, Chad G Cooper, James E Cox, Scott A Summers, Kimberley J Evason, Gregory S Ducker

bioRxiv [Preprint]. 2023 Oct 16:2023.10.12.562134. doi: 10.1101/2023.10.12.562134.

Palmitate-Induced Inflammation and Myotube Atrophy in C2C12 Cells Are Prevented by the Whey Bioactive Peptide, Glycomacropeptide

Naomi Mmp de Hart, Jonathan J Petrocelli, Rebekah J Nicholson, Elena M Yee, Patrick J Ferrara, Eric D Bastian, Loren S Ward, Brent L Petersen, Scott A Summers, Micah J Drummond

J Nutr. 2023 Oct;153(10):2915-2928. doi: 10.1016/j.tjnut.2023.08.033.Epub 2023 Aug 29.

New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative

Prasoona Karra, Sheetal Hardikar, Maci Winn 2 4, Garnet L Anderson, Benjamin Haaland, Benjamin Krick, Cynthia A Thomson, Aladdin Shadyab, Juhua Luo, Nazmus Saquib, Howard D Strickler, Rowan Chlebowski, Rhonda S Arthur, Scott A Summers, William L Holland, Thunder Jalili, Mary C Playdon

Cancer Epidemiol Biomarkers Prev. 2023 Oct 2;32(10):1356-1364. doi: 10.1158/1055-9965.EPI-23-0278.

Ceramides Increase Fatty Acid Utilization in Intestinal Progenitors to Enhance Stemness and Increase Tumor Risk

Ying Li, Bhagirath Chaurasia, M Mahidur Rahman, Vincent Kaddai, J Alan Maschek, Jordan A Berg, Joseph L Wilkerson, Ziad S Mahmassani, James Cox, Peng Wei, Peter J Meikle, Donald Atkinson, Liping Wang, Annelise M Poss, Mary C Playdon, Trevor S Tippetts, Esraa M Mousa 7, Kesara Nittayaboon 8, Pon Velayutham Anandh Babu 1, Micah J Drummond 5, Hans Clevers, James A Shayman, Yoshio Hirabayashi, William L Holland, Jared Rutter, Bruce A Edgar, Scott A Summers

Gastroenterology. 2023 Nov;165(5):1136-1150. doi: 10.1053/j.gastro.2023.07.017.

Placing a Hex on Glucose Uptake

Faith M Bowman

Diabetes. 2023 Jun 1;72(6):690-692. doi: 10.2337/dbi22-0040.

Writing and erasing ceramides to alter liver disease

Mariah Weber-Stout, Scott A Summers, William L Holland

Nature Metab. 2023 May;5(5):727-729. doi: 10.1038/s42255-023-00809-8.

Ceramides and Acute Kidney Injury

Rebekah J Nicholson, William L Holland, Scott A Summers.

Semin Nephrol. 2022 May;42(3):151281. doi: 10.1016/j.semnephrol.2022.10.007.Epub 2022 Nov 18.

The Use of Ceramides to Predict Metabolic Response to Metformin in Women With PCOS

Anu Sharma, Benjamin Krick, Ying Li, Scott A Summers, Mary C Playdon, Corrine Welt

J Endocr Soc. 2022 Sep 2;6(11):bvac131. doi: 10.1210/jendso/bvac131.eCollection 2022 Oct 11.

Metabolic dysfunction and obesity-related cancer: Results from the cross-sectional National Health and Nutrition Examination Survey

Maci Winn, Prasoona Karra, Benjamin Haaland, Jennifer A Doherty, Scott A Summers, Michelle L Litchman, Marc J Gunter, Mary C Playdon, Sheetal Hardikar

Cancer Med. 2023 Jan;12(1):606-618. doi: 10.1002/cam4.4912.Epub 2022 Jun 19.

Following Roux-en-Y gastric bypass surgery, serum ceramides demarcate patients that will fail to achieve normoglycemia and diabetes remission

Annelise M Poss, Benjamin Krick, J Alan Maschek, Benjamin Haaland, James E Cox, Prasoona Karra, Anna R Ibele, Steven C Hunt, Ted D Adams, William L Holland, Mary C Playdon, Scott A Summers

Med. 2022 Jul 8;3(7):452-467.e4. doi: 10.1016/j.medj.2022.05.011.Epub 2022 Jun 15.

Cordyceps inhibits ceramide biosynthesis and improves insulin resistance and hepatic steatosis

Ying Li, Chad Lamar Talbot, Bhawna Chandravanshi, Alec Ksiazek, Ayushi Sood, Kamrul Hasan Chowdhury, J Alan Maschek, James Cox, Adhini Kuppuswamy Satheesh Babu, Henry A Paz, Pon Velayutham Anandh Babu, David K Meyerholz, Umesh D Wankhade, William Holland, E Shyong Tai, Scott A Summers, Bhagirath Chaurasia

Sci Rep. 2022 May 4;12(1):7273. doi: 10.1038/s41598-022-11219-3.

Ceramide signaling in the gut

Ying Li, Rebekah J Nicholson, Scott A Summers.

Mol Cell Endocrinol. 2022 Mar 15:544:111554 doi: 10.1016/j.mce.2022.111554.

A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia

Simeone CA, Wilkerson JL, Poss AM, Banks JA, Varre JV, Guevara JL, Hernandez EJ, Gorsi B, Atkinson DL, Turapov T, Frodsham SG, Morales JCF, O'Neil K, Moore B, Yandell M, Summers SA, Krolewski AS, Holland WL, Pezzolesi MG.

NPJ Genom Med. 2022 Jul 22;7(1):43. PMID: 35869090

Following Roux-en-Y gastric bypass surgery, serum ceramides demarcate patients that will fail to achieve normoglycemia and diabetes remission

Poss AM, Krick B, Maschek JA, Haaland B, Cox JE, Karra P, Ibele AR, Hunt SC, Adams TD, Holland WL, Playdon MC, Summers SA.

Med (N Y). 2022 Jul 8;3(7):452-467.e4. Epub 2022 Jun 15.PMID: 35709767

The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease

Nicholson RJ, Norris MK, Poss AM, Holland WL, Summers SA.

Annu Rev Nutr. 2022 Aug 22;42:115-144. Epub 2022 May 18.PMID: 35584813

Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation

Castell AL, Vivoli A, Tippetts TS, Frayne IR, Angeles ZE, Moullé VS, Campbell SA, Ruiz M, Ghislain J, Des Rosiers C, Holland WL, Summers SA, Poitout V.

Diabetes. 2022 Jun 1;71(6):1218-1232. doi: 10.2337/db21-0640.PMID: 35287172

You aren't IMMUNE to the ceramides that accumulate in cardiometabolic disease

Varre JV, Holland WL, Summers SA.

Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jun;1867(6):159125. Epub 2022 Feb 23.PMID: 35218934

Cholesterol - the devil you know; ceramide - the devil you don't

Tippetts TS, Holland WL, Summers SA.

Trends Pharmacol Sci. 2021 Dec;42(12):1082-1095. Epub 2021 Nov 5.PMID: 34750017 Review.

Gutting out Myc to decrease ceramides

Li Y, Summers SA, Holland WL.

Nat Metab. 2021 Jul;3(7):890-891. PMID: 34211181

Ceramides and other sphingolipids as drivers of cardiovascular disease

Choi RH, Tatum SM, Symons JD, Summers SA, Holland WL.

Nat Rev Cardiol. 2021 Oct;18(10):701-711. Epub 2021 Mar 26.PMID: 33772258

Characterizing a Common CERS2 Polymorphism in a Mouse Model of Metabolic Disease and in Subjects from the Utah CAD Study

Nicholson RJ, Poss AM, Maschek JA, Cox JE, Hopkins PN, Hunt SC, Playdon MC, Holland WL, Summers SA.

J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3098-e3109. PMID: 33705551

Ceramides are necessary and sufficient for diet-induced impairment of thermogenic adipocytes

Chaurasia B, Ying L, Talbot CL, Maschek JA, Cox J, Schuchman EH, Hirabayashi Y, Holland WL, Summers SA.Mol Metab. 2021 Mar;45:101145. Epub 2020 Dec 19.PMID: 33352310

Metabolic Messengers: ceramides

Summers SA, Chaurasia B, Holland WL.

Nat Metab. 2019 Nov;1(11):1051-1058. Epub 2019 Oct 24.PMID: 32694860

Phospholipid methylation regulates muscle metabolic rate through Ca2+transport efficiency

Verkerke ARP, Ferrara PJ, Lin CT, Johnson JM, Ryan TE, Maschek JA, Eshima H, Paran CW, Laing BT, Siripoksup P, Tippetts TS, Wentzler EJ, Huang H, Spangenburg EE, Brault JJ, Villanueva CJ, Summers SA, Holland WL, Cox JE, Vance DE, Neufer PD, Funai K.

Nat Metab. 2019 Sep;1(9):876-885. Epub 2019 Sep 16.PMID: 32405618

Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults After Bed Rest.

Petrocelli JJ, McKenzie AI, Mahmassani ZS, Reidy PT, Stoddard GJ, Poss AM, Holland WL, Summers SA, Drummond MJ.J Gerontol A Biol Sci Med Sci. 2020 Sep 16;75(9):1663-1670. doi: 10.1093/gerona/glaa072.PMID: 32215553 Free PMC article.

Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease.

Poss AM, Maschek JA, Cox JE, Hauner BJ, Hopkins PN, Hunt SC, Holland WL, Summers SA, Playdon MC.J Clin Invest. 2020 Mar 2;130(3):1363-1376. doi: 10.1172/JCI131838.PMID: 31743112 Free PMC article. Clinical Trial.

FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection.

Karanth S, Chaurasia B, Bowman FM, Tippetts TS, Holland WL, Summers SA, Schlegel A.Physiol Rep. 2019 Sep;7(18):e14238. doi: 10.14814/phy2.14238.PMID: 31552709 Free PMC article.

Risky lipids: refining the ceramide score that measures cardiovascular health.

Poss AM, Holland WL, Summers SA.Eur Heart J. 2020 Jan 14;41(3):381-382. doi: 10.1093/eurheartj/ehz525.PMID: 31369077 No abstract available.

Targeting a ceramide double bond improves insulin resistance and hepatic steatosis.

Chaurasia B, Tippetts TS, Mayoral Monibas R, Liu J, Li Y, Wang L, Wilkerson JL, Sweeney CR, Pereira RF, Sumida DH, Maschek JA, Cox JE, Kaddai V, Lancaster GI, Siddique MM, Poss A, Pearson M, Satapati S, Zhou H, McLaren DG, Previs SF, Chen Y, Qian Y, Petrov A, Wu M, Shen X, Yao J, Nunes CN, Howard AD, Wang L, Erion MD, Rutter J, Holland WL, Kelley DE, Summers SA.Science. 2019 Jul 26;365(6451):386-392. doi: 10.1126/science.aav3722. Epub 2019 Jul 4.PMID: 31273070 Free PMC article.

Listen to your heart when ceramide's calling for higher glucose.

Wilkerson JL, Summers SA, Holland WL.EBioMedicine. 2019 Mar;41:3-4. doi: 10.1016/j.ebiom.2019.02.004. Epub 2019 Feb 7.PMID: 30738827 Free PMC article. No abstract available.

Strong Heart, Low Ceramides.

Holland WL, Summers SA.Diabetes. 2018 Aug;67(8):1457-1460. doi: 10.2337/dbi18-0018.PMID: 30030288 Free PMC article. No abstract available.

The ceramide ratio: a predictor of cardiometabolic risk.

Tippetts TS, Holland WL, Summers SA.J Lipid Res. 2018 Sep;59(9):1549-1550. doi: 10.1194/jlr.C088377. Epub 2018 Jul 9.PMID: 29987126 Free PMC article. No abstract available.

Does This Schlank Make Me Look Fat?

Chaurasia B, Holland WL, Summers SA.Trends Endocrinol Metab. 2018 Sep;29(9):597-599. doi: 10.1016/j.tem.2018.04.003. Epub 2018 Apr 21.PMID: 29685851 Free PMC article.

Ceramide-Initiated Protein Phosphatase 2A Activation Contributes to Arterial Dysfunction In Vivo.

Bharath LP, Ruan T, Li Y, Ravindran A, Wan X, Nhan JK, Walker ML, Deeter L, Goodrich R, Johnson E, Munday D, Mueller R, Kunz D, Jones D, Reese V, Summers SA, Babu PV, Holland WL, Zhang QJ, Abel ED, Symons JD.Diabetes. 2015 Nov;64(11):3914-26. doi: 10.2337/db15-0244. Epub 2015 Aug 7.PMID: 26253611 Free PMC article.

Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex.

Zhang QJ, Holland WL, Wilson L, Tanner JM, Kearns D, Cahoon JM, Pettey D, Losee J, Duncan B, Gale D, Kowalski CA, Deeter N, Nichols A, Deesing M, Arrant C, Ruan T, Boehme C, McCamey DR, Rou J, Ambal K, Narra KK, Summers SA, Abel ED, Symons JD.Diabetes. 2012 Jul;61(7):1848-59. doi: 10.2337/db11-1399. Epub 2012 May 14.PMID: 22586587 Free PMC article.

Fenretinide prevents lipid-induced insulin resistance by blocking ceramide biosynthesis.

Bikman BT, Guan Y, Shui G, Siddique MM, Holland WL, Kim JY, Fabriàs G, Wenk MR, Summers SA.J Biol Chem. 2012 May 18;287(21):17426-17437. doi: 10.1074/jbc.M112.359950. Epub 2012 Apr 2.PMID: 22474281 Free PMC article.

Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.

Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, Bulchand S, Knotts TA, Shui G, Clegg DJ, Wenk MR, Pagliassotti MJ, Scherer PE, Summers SA.J Clin Invest. 2011 May;121(5):1858-70. doi: 10.1172/JCI43378. Epub 2011 Apr 1.PMID: 21490391 Free PMC article.

Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin.

Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH, Davis KE, Bikman BT, Halberg N, Rutkowski JM, Wade MR, Tenorio VM, Kuo MS, Brozinick JT, Zhang BB, Birnbaum MJ, Summers SA, Scherer PE.Nat Med. 2011 Jan;17(1):55-63. doi: 10.1038/nm.2277. Epub 2010 Dec 26.PMID: 21186369 Free PMC article.

Ablation of AMP-activated protein kinase alpha2 activity exacerbates insulin resistance induced by high-fat feeding of mice.

Fujii N, Ho RC, Manabe Y, Jessen N, Toyoda T, Holland WL, Summers SA, Hirshman MF, Goodyear LJ.Diabetes. 2008 Nov;57(11):2958-66. doi: 10.2337/db07-1187. Epub 2008 Aug 26.PMID: 18728234 Free PMC article.

Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism.

Holland WL, Summers SA.Endocr Rev. 2008 Jun;29(4):381-402. doi: 10.1210/er.2007-0025. Epub 2008 May 1.PMID: 18451260 Free PMC article. Review.

Lipid mediators of insulin resistance.

Holland WL, Knotts TA, Chavez JA, Wang LP, Hoehn KL, Summers SA.Nutr Rev. 2007 Jun;65(6 Pt 2):S39-46. doi: 10.1111/j.1753-4887.2007.tb00327.x.PMID: 17605313 Review.

Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance.

Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, Narra K, Hoehn KL, Knotts TA, Siesky A, Nelson DH, Karathanasis SK, Fontenot GK, Birnbaum MJ, Summers SA.Cell Metab. 2007 Mar;5(3):167-79. doi: 10.1016/j.cmet.2007.01.002.PMID: 17339025

Acid ceramidase overexpression prevents the inhibitory effects of saturated fatty acids on insulin signaling.

Chavez JA, Holland WL, Bär J, Sandhoff K, Summers SA.J Biol Chem. 2005 May 20;280(20):20148-53. doi: 10.1074/jbc.M412769200. Epub 2005 Mar 17.PMID: 15774472