The incidence of insulin resistant states such as obesity and type 2 diabetes have been increasing at an alarming rate in recent years in both paediatric and adult populations. Our research program aims to elucidate the key genetic and environmental factors that link insulin resistance, lipoprotein abnormalities, and cardiovascular disease. We are investigating the underlying cellular and molecular mechanisms of the development of metabolic dyslipidaemia in insulin-resistant states. Using diet-induced animal models of insulin resistance and obesity, we are investigating the link between the insulin signalling pathway and deregulation of hepatic and intestinal lipoprotein metabolism. We also use these models to study the cellular and molecular mechanisms of hypolipidaemic and insulin-sensitizing drugs. Regulation of hepatic and intestinal apolipoprotein B gene expression is also under intense investigation, particularly at the posttranscriptional levels of protein translocation and intracellular degradation.

Rutlege A, Qiu W, Zhang J, Avramoglu-Kohen R, Nemat-Ghogani N, Adeli K . Mechanisms Targeting Apolipoprotein B100 to Proteasomal Degradation: Evidence that degradation is Initiated by BiP Binding at the N-Terminus and the Formation of a p97 Complex at the C-Terminus. Arterioscler Thromb Vasc Biol 2008. [Epub ahead of print]

Qiu W., Federico L., Naples M, Avramoglu-Kohen R., Meshkani R., Zhang J., Tsai J., Kontos CD, Horie Y., Suzuki A., and Adeli K . PTEN regulates hepatic lipogenesis, microsomal triglyceride transfer protein ( MTP ), and the secretion of apoB-containing lipoproteins. Hepatology 2008; 48(6):1799-1809.

Adeli K , Lewis GF. Intestinal lipoprotein overproduction in insulin-resistant states. Curr Opin Lipidol. 2008 June; 19(3): 221-8. (Invited Review)

Qin B, Anderson RA, Adeli K. Tumor necrosis factor-{alpha} directly stimulates the overproduction of hepatic apolopoprotein B100-containing VLDL via impairment of hepatic insulin signaling. Am J Physiol Gastrointest Liver Physiol. 2008 Mar 27.

Naples M, Federico LM, Xu E, Nelken J, Adeli K. Effect of rosuvastatin on insulin sensitivity in an animal model of insulin resistance: evidence for statin-induced hepatic insulin sensitization. Atherosclerosis 2008 May; 198(1): 94-103.

Nylen K , Velazquez JL , Likhodii SS , Cortez MA , Shen L , Leshchenko Y , Adeli K , Gibson KM , Burnham WM , Snead OC 3rd . A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype. Exp Neurol. 2008 Apr; 210(2): 449-57.

Miller A, Adeli K. Dietary frutctose and the metabolic syndrome. Curr Opin Gastroenterology. 2008 Mar:24(2): 204-9. (Invited Review)

Qin B., Qiu W. , Avramoglu-Kohen R, and Adeli K. Tumor Necrosis Factor-a Induces Intestinal Insulin Resistance and Stimulates the Assembly and Secretion of Apolipoprotein B48-containing Lipoproteins via Activation of the p38 MAP Kinase. Diabetes 2007 Feb;56(2):450-61.

Tsai J., Qiu W., Avramoglu-Kohen R, and Adeli K. MEK-ERK inhibition corrects the defect in VLDL assembly in HepG2 cells: Potential Role of ERK in VLDL-apoB100 Particle Assembly. Arterioscl. Thromb. Vasc. Biol. 2007 Jan;27(1):211-8.

Kelishadi R, Sharifi M, Khosravi A, Adeli K . Relationship Between C-Reactive Protein and Atherosclerotic Risk Factors and Oxidative Stress Markers Among Young Persons 10-18 Years Old. Clin Chem. 2007 Mar; 53(3):456-64.

Li L, Naples M, Song H, Yuan R, Ye F, Shafi S, Adeli K , Ng DS. LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E587-94.

Meshkani R, Taghikhani M, Al-Kateb H, Larijani B, Khatami S, Sidiropoulos GK, Hegele RA, Adeli K . Polymorphisms within the protein tyrosine phosphatase 1B (PTPN1) gene promoter: functional characterization and association with type 2 diabetes and related metabolic traits. Clin Chem. 2007 Sep;53(9):1585-92.

Federico L., Xia Z., Naples M., Taylor D., and Adeli K. Intestinal Insulin Resistance and Aberrant Production of Apolipoprotein B48 Lipoproteins in an Animal Model of Insulin Resistance: Evidence for activation of PTP-1B, ERK, and SREBP-1c in the fructose-fed hamster intestine. Diabetes 2006, 55(5):1316-26.

Qiu W, Avramoglu-Kohen R, Rutledge AC, Tsai J, Adeli K . Mechanisms of Glucosamine-induced Impairment in Hepatic Assembly and Secretion of Apolipoprotein B100-containing Lipoproteins. J. Lipid Res . 2006, 47(8):1749-61.

Chong T, Naples M, Federico L, Taylor D, Smith GJ, Cheung RC, Adeli K . Effect of rosuvastatin on hepatic production of apolipoprotein B-containing lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia. Atherosclerosis 2006; 185(1):21-31.

Morand J.P., Macri J, and Adeli K. Proteomic profiling of hepatic ER proteins in an animal model of insulin resistance and metabolic dyslipidemia. J. Biol Chem. 2005, 280(18):17626-33.

Sidiropoulos G., Pontrelli L., and Adeli K . Insulin-Mediated Suppression of Apolipoprotein B mRNA Translation Requires the 5' UTR and Is Characterized by Decreased Binding of an Insulin-Sensitive 110-kDa 5' UTR RNA-Binding Protein. Biochemistry 2005, 44(37):12572-81.

Qiu W, Taghibiglou C, Avramoglu RK, Van Iderstine SC, Naples M, Ashrafpour H, Mhapsekar S, Sato R, Adeli K. Oleate-mediated stimulation of microsomal triglyceride transfer protein ( MTP ) gene promoter: implications for hepatic MTP overexpression in insulin resistance. Biochemistry 2005, 44:3041-9.

Qiu W., Avramoglu-Kohen R., Mhapsekar, S., Tsai, J., Austin, R., Adeli K . Induction of ER Stress and Grp78 Selectively Promote Hepatic ApoB Degradation: Evidence for Grp78-Mediated Retention and Targeting to Proteasomal Degradation. Arterioscl. Thromb. Vas. Biol. 2005, 25(3):571-7.

Mielke JG, Taghibiglou C, Liu L, Zhang Y, Jia Z, Adeli K , Wang YT. A biochemical and functional characterization of diet-induced brain insulin resistance. J Neurochem. 2005 Jun;93(6):1568-78.

Lewis, G.F., Uffelman, K., Naples, M., Leung, N., Haidari, M., Szeto, L., Buckingham, R., Adeli, K . Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: studies in the fructose-fed Syrian Golden hamster. Endocrinology 2005 146(1): 247-255.

Qiu W., Kohen Avramoglu R., Dube N., Chong T.M., Naples M., Au C., Lewis G.F.L., Cohn J.S., Tremblay M.L., and Adeli K . Hepatic PTP-1B Expression Regulates the Assembly and Secretion of ApoB-Containing Lipoproteins: Evidence from PTP-1B overexpression, knockout and RNAi studies. Diabetes 2004, 53(12):3057-66.

Lewis,G.F, Leung,N., Watanabe,T., Uffelman,K., Szeto,L., Adeli, K . Intestinal lipoprotein production is stimulated by acute plasma FFA elevation: Studies in insulin resistant and insulin sensitized Syrian Golden hamsters. Endocrinology 2004 145(11):5006-12.

Uffelman,K.D., Murdoch,S., Leung,N., Naples,M., Szeto,L., Albers,A., Adeli, K ., Brunzell,J.D., and Lewis,G.F. Hepatic lipase mRNA, protein and plasma enzyme activity is increased in the insulin-resistant fructose-fed Syrian Golden hamster and is partially normalized by the insulin sensitizer, rosiglitazone. Diabetes 2004, 53(11):2893-900.