Endocrinology and Molecular Medicine
Lipid Metabolism, Atherosclerosis, Obesity, Adipocyte BiologyView Mary G. Sorci-Thomas, PhD Bio
Two projects are currently ongoing in Dr. Sorci-Thomas’ lab, both involve the protein PCPE2, or procollagen endopeptidase enhancer 2.
The first of these project examines the role of this novel protein, PCPE2 in regulating adipose tissue expansion during Western diet consumption. To do this an inducible adipocyte specific PCPE2 knockout mouse model was developed to study how the extracellular matrix protein participates in lipid uptake and efflux related to lipid storage. What we have found is that in the absence of adipocyte PCPE2, mice demonstrate reduced body weight, smaller fat stores, improved glucose tolerance and delayed postprandial lipid clearance, thus rendering them resistant to dietary fat-induced obesity and glucose intolerance. Future studies will focus on the molecular mechanism involved in PCPE2’s influence on lipid storage.
The second ongoing project in Dr. Sorci-Thomas’ lab focuses on a new and exciting concept of targeting inflammation to treat residual cardiovascular risk. Prior approaches have aimed at reducing inflammation by neutralizing the cytokine IL-1beta. Although this approach lowered CVD events, it also had serious side effects. In contrast, the new approach is aimed at increasing the function of “protective” circulating monocytes, termed, nonclassical monocytes (NCM). NCM make up ~10% of monocytes in blood and express 100-fold more scavenger receptor CD36 on their surface than classical monocytes. Traditionally monocytes have been viewed as simple precursors of macrophages which infiltrate the artery wall and contribute to foam cell burden in atherosclerotic plaque. But NCM are clearly distinct since once activated via CD36, they surveil and protect the luminal side of the vascular endothelium. NCM bind and crawl along the artery removing damaged endothelium and/or oxidized LDL (oxLDL) along their path. Thus, these studies will focus on stabilizing CD36 on NCM plasma membrane using a relatively understudied extracellular scaffold protein, procollagen endo-peptidase enhancer 2 (PCPE2).
Hao Xu, PhD
Marjorie Kipp, BS
N-terminal eGFP-tagging of rabbit apolipoprotein A-I decreases expression and impairs cholesterol-efflux activity.
(Wacker BK, Bi L, Liu L, Sorci-Thomas MG, Ng P, Palmer DJ, Tang C, Dichek DA.) Biochim Biophys Acta Mol Cell Biol Lipids. 2023 May;1868(5):159301 PMID: 36858111 PMCID: PMC10127936 SCOPUS ID: 2-s2.0-85150850823 03/02/2023
Regulation of Adipocyte Metabolic Homeostasis by SR-BI and PCPE2.
(Knaack DA, Sorci-Thomas MG, Thomas MJ, Chen Y, Sahoo D.) FASEB J. 2022 May;36 Suppl 1 PMID: 35553852 SCOPUS ID: 2-s2.0-85130030599 05/14/2022
Current models of apolipoprotein A-I lipidation by adenosine triphosphate binding cassette transporter A1.
(Hafiane A, Gianopoulos I, Sorci-Thomas MG, Daskalopoulou SS.) Curr Opin Lipidol. 2022 Apr 01;33(2):139-145 PMID: 34581311 SCOPUS ID: 2-s2.0-85125682549 09/29/2021
(Natarajan R, Moore K, Sahoo D, Nana-Sinkam P, Fowler AAB 3rd, Sime P, Sorci-Thomas M, Aikawa E, ATVB Council, friends, and colleagues.) Arterioscler Thromb Vasc Biol. 2022 Mar;42(3):239-240 PMID: 36808997 SCOPUS ID: 2-s2.0-85148678313 02/23/2023
Apolipoprotein A-I carboxy-terminal domain residues 187-243 are required for adiponectin-induced cholesterol efflux.
(Hafiane A, Gianopoulos I, Sorci-Thomas MG, Daskalopoulou SS.) Cell Signal. 2022 Mar;91:110222 PMID: 34954016 SCOPUS ID: 2-s2.0-85121847439 12/27/2021
Downregulation of low-density lipoprotein receptor mRNA in lymphatic endothelial cells impairs lymphatic function through changes in intracellular lipids.
(Vachon L, Smaani A, Tessier N, Jean G, Demers A, Milasan A, Ardo N, Jarry S, Villeneuve L, Alikashani A, Finherty V, Ruiz M, Sorci-Thomas MG, Mayer G, Martel C.) Theranostics. 2022;12(3):1440-1458 PMID: 35154499 PMCID: PMC8771568 SCOPUS ID: 2-s2.0-85122672999 02/15/2022
Downregulation of low-density lipoprotein receptor mRNA in lymphatic endothelial cells impairs lymphatic function through changes in intracellular lipids
(Vachon L, Smaani A, Tessier N, Jean G, Demers A, Milasan A, Ardo N, Jarry S, Villeneuve L, Alikashani A, Finherty V, Ruiz M, Sorci-Thomas MG, Mayer G, Martel C.) Theranostics. 2022;12(3):1440-1458 SCOPUS ID: 2-s2.0-85122672999 01/01/2022
Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI-Mediated High-Density Lipoprotein Uptake.
(Xu H, Thomas MJ, Kaul S, Kallinger R, Ouweneel AB, Maruko E, Oussaada SM, Jongejan A, Cense HA, Nieuwdorp M, Serlie MJ, Goldberg IJ, Civelek M, Parks BW, Lusis AJ, Knaack D, Schill RL, May SC, Reho JJ, Grobe JL, Gantner B, Sahoo D, Sorci-Thomas MG.) Arterioscler Thromb Vasc Biol. 2021 Nov;41(11):2708-2725 PMID: 34551590 PMCID: PMC8551036 SCOPUS ID: 2-s2.0-85118592107 09/24/2021
Myeloperoxidase Inhibition Ameliorates Plaque Psoriasis in Mice.
(Neu SD, Strzepa A, Martin D, Sorci-Thomas MG, Pritchard KA Jr, Dittel BN.) Antioxidants (Basel). 2021 Aug 25;10(9) PMID: 34572970 PMCID: PMC8472607 09/29/2021
Enterically derived high-density lipoprotein restrains liver injury through the portal vein.
(Han YH, Onufer EJ, Huang LH, Sprung RW, Davidson WS, Czepielewski RS, Wohltmann M, Sorci-Thomas MG, Warner BW, Randolph GJ.) Science. 2021 Jul 23;373(6553) PMID: 34437091 PMCID: PMC8478306 SCOPUS ID: 2-s2.0-85111031761 08/27/2021
Myeloperoxidase inhibition ameliorates plaque psoriasis in mice
(Neu SD, Strzepa A, Martin D, Sorci-Thomas MG, Pritchard KA, Dittel BN.) Antioxidants. September 2021;10(9) SCOPUS ID: 2-s2.0-85113363981 09/01/2021
Enterically derived high-density lipoprotein restrains liver injury through the portal vein
(Han YH, Onufer EJ, Huang LH, Sprung RW, Davidson WS, Czepielewski RS, Wohltmann M, Sorci-Thomas MG, Warner BW, Randolph GJ.) Science. 23 July 2021;373(6553) SCOPUS ID: 2-s2.0-85111031761 07/23/2021