Lin Zhu, M.D., Ph.D.

Research Assistant Professor

lin.zhu@vanderbilt.edu
Faculty Appointments
Research Assistant Professor of Medicine
Education
Ph.D., University of Guelph, Ontario, CanadaM.D., Tianjin Medical College, Tianjin, China
Research Description
Dr. Zhu’s research interest is to understand the relationship between energy homeostasis and inflammation, which might be a foundational mechanism for insulin resistance, hyperlipidemia, and atherosclerosis. Her research focuses on the use of mouse disease models to identify mechanisms that underlie insulin resistance and atherosclerosis. She aims to define fundamental principles of how to improve HDL function for patients with type-2 diabetes to reduce cardiovascular disease. During Dr. Zhu’s graduate studies, she studied the regulation of PCYT2, a rate-limiting enzyme for phospholipid synthesis, at transcriptional and posttranscriptional levels. This work resulted in seven publications with four of them as the first author. During her training as a postdoctoral fellow in the Division of Cardiovascular Medicine at Vanderbilt, Dr. Zhu demonstrated that LRP1-deficient macrophages caused inflammatory responses in the artery walls due to the impaired ability of foam cells to clear the plaque. In another high-impact project, she found that anti-inflammatory macrophages promoted cholesterol reverse transport and macrophage migration out of artery walls, leading to atherosclerosis regression. This novel discovery may set up a platform to develop therapeutic policies to prevent cardiovascular events. During her training in the Division of Diabetes, Endocrinology, and Metabolism at Vanderbilt, Dr. Zhu showed that deletion of liver estrogen receptor alpha led to lipid accumulation in the liver and caused whole body insulin resistance. One of her ongoing projects shows that a clinically used CETP inhibitor increases HDL cholesterol; however, it also increases inflammatory responses and causes insulin resistance in obese mice. This study may explain the reason why clinical trials using CETP inhibitors have failed to prevent cardiovascular disease.
Publications
Palmisano BT, Zhu L, Litts B, Burman A, Yu S, Neuman JC, Anozie U, Luu TN, Edington EM, Stafford JM. Hepatocyte Small Heterodimer Partner Mediates Sex-Specific Effects on Triglyceride Metabolism via Androgen Receptor in Male Mice. Metabolites. 2021 May 5/20/2021; 11(5): PMID: 34065318, PMCID: PMC8161262, PII: metabo11050330, DOI: 10.3390/metabo11050330, ISSN: 2218-1989.

Palmisano BT, Yu S, Neuman JC, Zhu L, Luu T, Stafford JM. Low-density lipoprotein receptor is required for cholesteryl ester transfer protein to regulate triglyceride metabolism in both male and female mice. Physiol Rep. 2021 Feb; 9(4): e14732. PMID: 33625789, PMCID: PMC7903989, DOI: 10.14814/phy2.14732, ISSN: 2051-817X.

Zhu L, An J, Chinnarasu S, Luu T, Pettway YD, Fahey K, Litts B, Kim HH, Flynn CR, Linton MF, Stafford JM. Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice. Front Physiol. 2021; 12: 799096. PMID: 35082691, PMCID: PMC8784660, DOI: 10.3389/fphys.2021.799096, ISSN: 1664-042X.

Palmisano BT, Anozie U, Yu S, Neuman JC, Zhu L, Edington EM, Luu T, Stafford JM. Cholesteryl Ester Transfer Protein Impairs Triglyceride Clearance via Androgen Receptor in Male Mice. Lipids [print-electronic]. 2021 Jan; 56(1): 17-29. PMID: 32783209, PMCID: PMC7818496, DOI: 10.1002/lipd.12271, ISSN: 1558-9307.

Mueller PA, Zhu L, Tavori H, Huynh KT, Giunzioni I, Stafford JM, Linton MF, Fazio S. Response by Mueller et al to Letter Regarding Article, "Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages" [letter]. Circulation. 2019 Apr 4/16/2019; 139(16): 1983-4. PMID: 30986111, PMCID: PMC7447072, DOI: 10.1161/CIRCULATIONAHA.119.039682, ISSN: 1524-4539.

Zhu L, Luu T, Emfinger CH, Parks BA, Shi J, Trefts E, Zeng F, Kuklenyik Z, Harris RC, Wasserman DH, Fazio S, Stafford JM. CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on a High-Fat Diet. Diabetes [print-electronic]. 2018 Dec; 67(12): 2494-506. PMID: 30213825, PMCID: PMC6245220, PII: db18-0474, DOI: 10.2337/db18-0474, ISSN: 1939-327X.

Mueller PA, Zhu L, Tavori H, Huynh K, Giunzioni I, Stafford JM, Linton MF, Fazio S. Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages. Circulation. 2018 Oct 10/23/2018; 138(17): 1850-63. PMID: 29794082, PMCID: PMC6343494, PII: CIRCULATIONAHA.117.031702, DOI: 10.1161/CIRCULATIONAHA.117.031702, ISSN: 1524-4539.

Palmisano BT, Zhu L, Eckel RH, Stafford JM. Sex differences in lipid and lipoprotein metabolism. Mol Metab [print-electronic]. 2018 Sep; 15: 45-55. PMID: 29858147, PMCID: PMC6066747, PII: S2212-8778(18)30315-6, DOI: 10.1016/j.molmet.2018.05.008, ISSN: 2212-8778.

Zhu L, Shi J, Luu TN, Neuman JC, Trefts E, Yu S, Palmisano BT, Wasserman DH, Linton MF, Stafford JM. Hepatocyte estrogen receptor alpha mediates estrogen action to promote reverse cholesterol transport during Western-type diet feeding. Mol Metab [print-electronic]. 2018 Feb; 8: 106-16. PMID: 29331506, PMCID: PMC5985047, PII: S2212-8778(17)30683-X, DOI: 10.1016/j.molmet.2017.12.012, ISSN: 2212-8778.

Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017; 1043: 227-56. PMID: 29224098, PMCID: PMC5763482, DOI: 10.1007/978-3-319-70178-3_12, ISSN: 0065-2598.

Zhu L, Giunzioni I, Tavori H, Covarrubias R, Ding L, Zhang Y, Ormseth M, Major AS, Stafford JM, Linton MF, Fazio S. Loss of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-a Inhibition. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2016 Aug; 36(8): 1483-95. PMID: 27365402, PMCID: PMC5346022, PII: ATVBAHA.116.307736, DOI: 10.1161/ATVBAHA.116.307736, ISSN: 1524-4636.

Palmisano BT, Le TD, Zhu L, Lee YK, Stafford JM. Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice. J. Lipid Res [print-electronic]. 2016 Aug; 57(8): 1541-51. PMID: 27354419, PMCID: PMC4959869, PII: jlr.M069013, DOI: 10.1194/jlr.M069013, ISSN: 1539-7262.

Tavori H, Fan D, Giunzioni I, Zhu L, Linton MF, Fogo AB, Fazio S. Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice. J. Lipid Res [print-electronic]. 2014 Oct; 55(10): 2073-81. PMID: 25183802, PMCID: PMC4174000, PII: jlr.M049874, DOI: 10.1194/jlr.M049874, ISSN: 1539-7262.

Zhu L, Martinez MN, Emfinger CH, Palmisano BT, Stafford JM. Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity. Am. J. Physiol. Endocrinol. Metab [print-electronic]. 2014 May 5/15/2014; 306(10): E1188-97. PMID: 24691030, PMCID: PMC4116406, PII: ajpendo.00579.2013, DOI: 10.1152/ajpendo.00579.2013, ISSN: 1522-1555.

Luo P, Dematteo A, Wang Z, Zhu L, Wang A, Kim HS, Pozzi A, Stafford JM, Luther JM. Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice. Diabetologia [print-electronic]. 2013 Apr; 56(4): 901-10. PMID: 23314847, PMCID: PMC3593801, DOI: 10.1007/s00125-012-2814-8, ISSN: 1432-0428.