{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:13:14Z","timestamp":1791915194517,"version":"4.3.4"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01 GM115367-01"],"award-info":[{"award-number":["1R01 GM115367-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Obesity has achieved epidemic status in the United States, resulting in an increase in type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease. Numerous studies have shown that inflammation plays a key role in the development of insulin resistance and diabetic complications. HDL cholesterol levels are inversely associated with coronary heart disease in humans. The beneficial effect of HDL is due, in part, to apolipoproteins A-I and E, which possess anti-inflammatory properties. The functional quality of HDL, however, may be reduced in the context of diabetes. Thus, raising levels of functional HDL is an important target for reducing inflammation and diabetic complications. Apo A-I possesses eight alpha-helical sequences, most of which form class A amphipathic helical structures. Peptides belonging to this class inhibit atherogenesis in several mouse models. Additional peptides based on structural components of apoE have been shown to mediate a rapid clearance of atherogenic lipoproteins in dyslipidemic mice. In this review, we discuss the efficacy of apolipoprotein mimetic peptides in improving lipoprotein function, reducing inflammation, and reversing insulin resistance and cardiometabolic disease processes in diabetic animals.<\/jats:p>","DOI":"10.3390\/biom11050627","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T12:08:30Z","timestamp":1619179710000},"page":"627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Apolipoprotein Mimetic Peptides: An Emerging Therapy against Diabetic Inflammation and Dyslipidemia"],"prefix":"10.3390","volume":"11","author":[{"given":"Paul","family":"Wolkowicz","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Roger","family":"White","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. M.","family":"Anantharamaiah","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1161\/01.CIR.0000089189.70578.E2","article-title":"Diabetes and Vascular Disease","volume":"108","author":"Luscher","year":"2003","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.2337\/diacare.27.6.1496","article-title":"Lipids and Lipoproteins in Type 2 Diabetes","volume":"27","author":"Krauss","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1161\/01.ATV.0000053385.64132.2D","article-title":"Smallest LDL Particles are Most Strongly Related to Coronary Disease Progression in Men","volume":"23","author":"Williams","year":"2003","journal-title":"Arteriosclr. Throm. Vasc. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"614","DOI":"10.2337\/diacare.20.4.614","article-title":"Cholessterol Lowering with Simvastatin Improves Prognosis of Diabetic Patients with Coronary Heart Disease: A Subgroup Ananysis of Scandinavian Simvastatin Survival Study (4S)","volume":"20","author":"Pyrala","year":"1997","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrcardio.2010.222","article-title":"HDL and Cardiovascular Disease: Atherogenic and Atheroprotective Mechanisms","volume":"8","author":"Navab","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-020-02860-3","article-title":"High-Density Lipoproteins during Sepsis: From Bench to Bedside","volume":"24","author":"Tanaka","year":"2020","journal-title":"Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1001\/jama.1986.03380200073024","article-title":"Incedence of Coronary Heart Disease and Lipoprotein Cholesterol levels: The Framingham Study","volume":"256","author":"Castelli","year":"1986","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/bmj.b92","article-title":"Association between Change in High Density Lipoprotein Cholesterol and Cardiovascular Disease Morbidity and Mortality: Systematic Review and Meta-Regression Analysis","volume":"338","author":"Briel","year":"2009","journal-title":"BMJ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1093\/eurheartj\/ehx274","article-title":"HDL Cholesterol Concentration or HDL Function: Which Matters?","volume":"38","author":"Barter","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nrendo.2011.235","article-title":"The Emerging Role of HDL in Glucose Metabolism","volume":"8","author":"Drew","year":"2012","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.2337\/db14-1603","article-title":"HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study","volume":"64","author":"Haase","year":"2015","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nm1546","article-title":"Beta-Cell ABCA1 Influences Insulin Secretion, Glucose Homeostasis and Response to Thiazolidinedione Treatment","volume":"3","author":"Brunham","year":"2007","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1161\/CIRCULATIONAHA.108.843219","article-title":"High-Density Lipoprotein Modulates Glucose Metabolism in Patients with Type 2 Diabetes Mellitus","volume":"119","author":"Drew","year":"2009","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S0140-6736(14)61217-4","article-title":"HDL and Cardiovascular Disease","volume":"384","author":"Rader","year":"2014","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1161\/CIRCRESAHA.114.300935","article-title":"High Density Lipoprotein: Vascular Protective Effects, Dysfunction and Potential as Therapeutic Target","volume":"114","author":"Landmesser","year":"2014","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1161\/01.CIR.0000103624.14436.4B","article-title":"Inflammatory\/Anti-Inflammatory Properties of High Density Lipoprotein Distinguish Patients from Control Subjects Better than HDL Cholesterol Levels and are Favorably Affected by Simvastatin Treatment","volume":"108","author":"Ansell","year":"2003","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11010-017-3165-z","article-title":"Dysfunctional HDL in Diabetes Mellitus and its Role in the Pathogenesis of Cardiovascular Disease","volume":"440","author":"Srivastava","year":"2018","journal-title":"Mol. Cell Biochem."},{"key":"ref_18","first-page":"19361","article-title":"Dyslipidemia and Diabetes","volume":"19","author":"Orchared","year":"1991","journal-title":"Endocrinnol. Metabol. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s00125-006-0574-z","article-title":"The Impact of Glycation on Apolipoprotein A-I Structure and its Ability to Activate Lecithin: Cholesterol Acyltransferase","volume":"50","author":"Nobercourt","year":"2017","journal-title":"Diabetologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1463-1326.2008.01012.x","article-title":"Reverse Cholesterol Transport in Type2 Diabetes Mellitus","volume":"11","author":"Tan","year":"2009","journal-title":"Diabetes Obes. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1161\/ATVBAHA.116.307385","article-title":"Impaired Cholesterol Efflux Capacity of High-Density Lipoprotein Isolated from Interstitial Fluid in Type 2 Diabetes Mellitus\u2014Brief Report","volume":"36","author":"Apro","year":"2016","journal-title":"Athero. Thromb. Vasc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s00109-005-0030-4","article-title":"Role of apoA-I, ABCA1, LCAT, and SR-BI in the Biogenesis of HDL","volume":"84","author":"Zannis","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.2337\/dc12-1411","article-title":"Glycation of Apoprotein A-I is Associated with Coronary Artery Plaque Progression in Type 2 Diabetic Patients","volume":"36","author":"Pu","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1007\/s00125-007-0752-7","article-title":"Apolipoprotein A-I Stimulates AMP-Activated Protein Kinase and Improves Glucose Metabolism","volume":"50","author":"Han","year":"2007","journal-title":"Diabetologia"},{"key":"ref_25","first-page":"47","article-title":"Lysine Glycation of Apolipoprotein A-I Impairs Its Anti-Inflammatory Properties in Type 2 Diabetes Mellitus","volume":"122","author":"Liu","year":"2018","journal-title":"J. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1007\/s00125-007-0718-9","article-title":"Advanced glycation of alolipoprotein A-I impairs its anti-atherogenic properties","volume":"50","author":"Han","year":"2007","journal-title":"Diabitologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1194\/jlr.R012658","article-title":"Sequence Conservation of Apolipoprotein A-I Affords Novel Insights into HDL Structure-Function","volume":"52","author":"Bashtovyy","year":"2011","journal-title":"J. Lipid. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/01.ATV.16.2.328","article-title":"Only the Two End Helixes of Eight Tandem Amphipathic Helical Domains of Human Apo A-I have Significant Lipid Affinity: Implications for HDL Assembly","volume":"16","author":"Palgunachari","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1074\/mcp.RA118.000878","article-title":"Apolipoprotein A1 Forms 5\/5 and 5\/4 Antiparallel Dimers in Human High-density Lipoprotein","volume":"18","author":"He","year":"2019","journal-title":"Mol. Cell Proteomics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.2337\/dbi20-0035","article-title":"A New Treatment Strategy for Diabetic Dyslipidemia?","volume":"69","author":"Kothari","year":"2020","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10248","DOI":"10.1016\/S0021-9258(17)39238-4","article-title":"Studies of Synthetic Peptide Analogs of the Amphipathic Helix. Structure of Complexes with Dimyristoyl Phosphatidylcholine","volume":"260","author":"Anantharamaiah","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0065-3233(08)60643-9","article-title":"The Amphipathic Helix in Exchangeable Apolipoproteins: A Multifunctional and Structural Motif in Plasma Apolipoproteins","volume":"45","author":"Segrest","year":"1994","journal-title":"Adv. Protein. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0022-2275(20)31163-9","article-title":"A New Synthetic Class A Amphipathic Peptide Analogue Protects Mice from Diet-Induced Atherosclerosis","volume":"42","author":"Garber","year":"2001","journal-title":"J. Lipid. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1194\/jlr.M800046-JLR200","article-title":"L-4F Treatment Reduces Adiposity, Increases Adiponectin Levels, and Improves Insulin Sensitivity in Obese Mice","volume":"49","author":"Peterson","year":"2008","journal-title":"J. Lipid. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1194\/jlr.M800610-JLR200","article-title":"The L-4F Mimetic Peptide Prevents Insulin Resistance through Increased Levels of HO-1, pAMPK, and pAKT in Obese Mice","volume":"50","author":"Peterson","year":"2009","journal-title":"J. Lipid. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1161\/CIRCULATIONAHA.104.517102","article-title":"D-4F Induces Heme Oxygenase-1 and Extracellular Superoxide Dismutase, Decreases Endothelial Cell Sloughing, and Improves Vascular Reactivity in Rat Model of Diabetes","volume":"111","author":"Kruger","year":"2005","journal-title":"Circulation"},{"key":"ref_37","unstructured":"Anantharamaiah, G.M., and Goldberg, D. (2015). ApoA-I Mimetic Peptides and Diabetes. Apolipoprotein Mimetics in the Management of Human Disease, Springer International Publishing."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1152\/ajpheart.00850.2012","article-title":"Apolipoprotein A-1 Mimetic D-4F Enhances Isoflurane-Induced eNOS Signaling and Cardioprotection during Acute Hyperglycemia","volume":"305","author":"Baotic","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.2337\/db10-0844","article-title":"Apolipoprotein A-I Mimetic Peptides Prevent Atherosclerosis Development and Reduce Plaque Inflammation in a Murine Model of Diabetes","volume":"59","author":"Morgantini","year":"2010","journal-title":"Diabetes"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1155\/2012\/628147","article-title":"Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway","volume":"2012","author":"Cao","year":"2012","journal-title":"Int. J. Hypertens."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-2275(20)33334-4","article-title":"Remnant Lipoprotein Metabolism: Key Pathways Involving Cell-Surface Heparin Sulfate Proteoglycans and Apolipoprotein E","volume":"40","author":"Mahley","year":"1999","journal-title":"J. Lipid. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1172\/JCI67398","article-title":"Apolipoprotein E and AV Mediate Lipoprotein Clearance by Hepatic Proteoglycans","volume":"135","author":"Gonzales","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1161\/01.ATV.0000154570.50696.2c","article-title":"Apolipoprotein E and Atherosclerosis:Beyond Lipid Effect","volume":"25","author":"Davignon","year":"2005","journal-title":"Arterio. Thromb. Vasc. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0065-3233(08)60642-7","article-title":"Apolipoprotein E: Structure-Function Relationship","volume":"45","author":"Weisgraber","year":"1994","journal-title":"Adv. Protein. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1021\/bi991209w","article-title":"The Receptor Binding Domain of apoE, Linked to a Model Class A Amphipathic Helix., Enhances Internalization and Degradation of LDL by Fibroblasts","volume":"39","author":"Datta","year":"2000","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.atherosclerosis.2012.10.064","article-title":"Two Apolipoprotein E Mimetic Peptides with Similar Cholesterol Reducing Properties Exhibit Different Atheroprotective Effects in apoE Null Mice","volume":"227","author":"Handattu","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1161\/CIRCULATIONAHA.104.497107","article-title":"Apolipoprotein E Mimetic Peptide Dramatically Lowers Plasma Cholesterol and Restores Endothelial Function in Watanabe Heritable Hyperlipidemic Rabbits","volume":"111","author":"Gupta","year":"2005","journal-title":"Circulation"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.atherosclerosis.2012.05.040","article-title":"Apolipoprotein E Mimetic Peptide is More Effective than Apolipoprotein A-I Mimetic in Reducing Lesion Formation in Older apoE Null Mice","volume":"224","author":"Nayyar","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1194\/jlr.R051367","article-title":"Anti-Inflammatory and Cholesterol Reducing Properties of Apolipoprotein Mimetics: A Review","volume":"55","author":"White","year":"2014","journal-title":"J. Lipid. Res."},{"key":"ref_50","unstructured":"White, R.C., and Anantharamaiah, G.M. Unpublished Results."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1194\/jlr.M085985","article-title":"Novel Fatty Acyl apoE Mimetic Peptides have Increased Potency to Reduce Plasma Cholesterol in Mice and Macaques","volume":"59","author":"Anantharamaiah","year":"2018","journal-title":"J. Lipid. Res."},{"key":"ref_52","first-page":"15","article-title":"The Apolipoprotein E Mimetic Peptide AEM-2 Attenuates Mitochondrial Injury and Apoptosis in Human THP-1 Macrophages","volume":"19","author":"Datta","year":"2018","journal-title":"Curr. Top. Pept. Protein. Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/627\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:42Z","timestamp":1760161902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/5\/627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,23]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["biom11050627"],"URL":"https:\/\/doi.org\/10.3390\/biom11050627","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,23]]}}}