About Sickkids
About SickKids
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Khosrow Adeli , PhD, FCACB, DABCC, FACB

The Hospital for Sick Children
Division Head
Clinical Biochemistry

Research Institute
Senior Associate Scientist
Molecular Structure & Function

University of Toronto
Professor
Department of Biochemistry

Professor
Department of Laboratory Medicine & Pathobiology

Phone: 416-813-8682
Fax: 416-813-6257
e-mail: khosrow.adeli@sickkids.ca

For more information, visit: Adeli Lab

Research Interests

  • Molecular mechanisms of dyslipidemia
  • Lipoprotein metabolism
  • ApoB gene expression
  • Animal models of obesity and insulin resistance
  • Hyperlipidemia in insulin resistance and type 2 diabetes

Research activities

Molecular and cellular biology of lipoprotein metabolism in insulin-resistant states such as obesity and diabetes, and the link with cardiovascular disease

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.

Publications

2010

Blasutig IM, Jung B, Kulasingam V, Baradaran S, Chen Y, Chan MK, Colantonio D, Adeli K.  Analytical evaluation of the VITROS® 5600 Integrated System in a pediatric setting and determination of pediatric reference intervals.  Clin Biochem.  2010: 43(13-14); 1039-44. 

Kulasingam V, Jung B, Blasutig IM, Baradaran S, Chan MK, Aytekin M, Colantonio DA, Adeli K.  Pediatric reference intervals for 28 chemistries and immunoassays on the Roche Cobas® 6000 analyzer – a CALIPER pilot study.  Clin Biochem. 2010: 43(13-14); 1045-50.

Rutledge A, Su Q, Adeli K.  Apolipoprotein B100 biogenesis: a complex array of intracellular mechanisms regulating folding, stability and lipoprotein assembly.  Biochem Cell Biol 2010: 88(2); 261-67.

O’Gorman CS, Simoneau-Roy J, Pencharz P, Macfarlane J, Maclusky I, Narang I, Adeli K, Daneman D, Hamilton J.  Sleep-disordered breathing is increased in obese adolescents with craniopharyngioma compared with obese controls.  J Clin Endocrinol Metab.  2010: 95(5); 2211-8.

Bakhtiyari S, Meshkani R, Taghikhani M, Larijani B, Adeli K.  Protein tyrosine phosphatase-1B (PTP-1B) knockdown improves palmitate-induced insulin resistance in C2C12 skeletal muscles.  Lipids.  2010: 45(3); 237-44.

Wong DM, Webb JP, Malinowski PM, Xu E, Macri J, Adeli K.  Proteomic profiling of intestinal prechylomicron transport vesicle (PCTV)-associated proteins in an animal model of insulin resistance (94 char).  J Proteomics.  2010; 73(7): 1291-305.

Meng Q, Adeli K, Zello G, Porter W, Krahn J.  Elevated lactate in ethylene glycol poisoning: true or false?  Clin Chim Acta.  2010; 411(7-8): 601-4.

Dong B, Wu M, Li H, Kraemer FB, Adeli K, Seidah NG, Park SW, Liu J.  Strong induction of PCSK9 gene expression through HNF1{alpha} and SREPB2: mechanisms for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters.  J Lipid Res.  2010: 51(6); 1486-95.

Hsieh J, Longuet C, Baker CL, Qin B, Federico LM, Drucker DJ, Adeli K.  The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and secretion in hamsters and mice.  Diabetologia.  2010; 53(3): 552-61.

2009

Li H, Adeli K.  Laboratory quality regulations and accreditation standards in Canada.  Clin Biochem.  2009; 42(4-5): 249-55.

Ragheb R, Shanab GM, Medhat AM, Deoudi DM, Adeli K, Fantus IG.  Free fatty acid-induced muscle insulin resistance and glucose uptake dysfunction: evidence for PKC activation and oxidative stress-activated signaling pathways.  Biochem Biophys Res Commun.  2009; 389(2): 211-6.

Gong Y, Adeli K.  A national survey on pediatric critical values used in clinical laboratories across Canada.  Clin Biochem.  2009; 42(16-17): 1610-5.

Wong DM, Webb JP, Malinowski PM, Macri J, Adeli K.  Proteomic profiling of the prechylomicron transport vesicle involved in the assembly and secretion of apoB-48-containing chylomicrons in the intestinal enterocytes.  Proteomics.  2009; 9(14): 3698-711.

Jung B, Adeli K.  Clinical laboratory reference intervals in pediatrics:  The CALIPER intitiative.  Clin Biochem.  2009; 42(16-17): 1589-95.

Schnabl KL, Sibbald M, Gold WL, Chan PC, Adeli K.  A patient with a leg rash, pedal edema, renal failure, and thrombocytopenia.  Clin Chem.  2009; 55(7): 1419-22; discussion 1423-4.

Basciano H, Miller AE, Naples M, Baker C, Kohen R, Xu E, Su Q, Allister E, Wheeler M, Adeli K.  Metabolic effects of dietary cholesterol in an animal model of insulin resistance nad hepatic steatosis.  Am J Physiol Endrocrinol Metab.  2009; 297(2): E462-73.

Meshkani R, Adeli K.  Hepatic insulin resistance, metabolic syndrome and cardiovascular disease.  Clinical Biochemistry.  2009; 42(13-14): 1331-46.

Basciano H, Miller AE, Baker C, Naples M, Adeli K.  LXR alpha activation perturbs hepatic insulin signaling and stimulates production of apolipoprotein B-containing lipoproteins.  Am J Physiol Gastrointest Liver Physiol 2009; 297(2): G323-32.

Simoneau-Roy J, O’Gorman C, Pencharz P, Adeli K, Daneman D, Hamilton J.  Insulin sensitivity and secretion in children and adolescents with hypothalamic obesity following treatment for craniopharyngioma.  Clin Endocrinol (Oxf)  2009; 72(3): 364-70.

Hsieh J, Longuet C, Maida A, Bahrami J, Xu E, Baker CL, Brubaker PL, Drucker DJ, Adeli K.  Glucagon-like peptide-1 increases intestinal lipid absorption and chylomicron production via CD36.  Gastroenterology.  2009; 137(3): 997-1005.

Rose JB, Ellis L, John B, Martin S, Gonska T, Soloman M, Tullis E, Corey M, Adeli K, Durie PR.  Does the Macroduct (®) collection system reliably define sweat chloride concentration in subjects with intermediate results?  Clinical Biochemistry.  2009; 42(12): 1260-4.

Wong D., Webb J., Malinowski P, Macri J., Adeli K. Proteomic profiling  of the prechylomicron transport besicle (PCTV) involved in the assembly and secretion of apoB48-containing chylomicrons in the intestinal enterocytes. Mol. Cell. Proteomics 2009; 9(14): 3698-711.

Qiu W, Su Q, Zhang J, Adeli K. Glucosamine-induced ER stress attenuates apolipoprotein B100 synthesis via PERK signaling. J Lipid Res. 2009; 50(9): 1814-23.

Su Q, Tsai J, Qiu W, Adeli K. Apolipoprotein B100 acts as a molecular link between lipid-induced ER stress and hepatic insulin resistance. Hepatology 2009; 50(1): 77-84.

Tsai J, Zhang R, Qiu W, Su Q, Naples M, Adeli K. Inflammatory NFkB activation promotes hepatic apolipoprotein B100 secretion: evidence for a link between hepatic inflammation and lipoprotein production. Am J Physiol Gastrointest Liver Physiol 2009; 296(6): G1287-98.

Wong D, Adeli K. Microsomal proteomics. Methods Mol. Biol. 2009;519:273-289.

Sirek AS, Liu L, Naples M, Adeli K, Ng DS, Jin T. Insulin stimulates the expression of carbohydrate response element binding protein (ChREBP) by attenuating the repressive effect of POU homeodomain protein Oct-1. Endocrinology 2009; 150(8): 3483-92.

Chan MK, Seiden-Long I, Aytekin M, Quinn F, Ravalico T, Ambruster D, Adeli K.  Canadian laboratory initiative on pediatric reference interval database (CALIPER): pediatric reference intervals for an integrated chemistry and immunoassay analyzer, Abbott Architect ci8200.  Clinical Biochemistry 2009; 42(9): 885-91.

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 2009; 29(4): 579-85.

2008

Qiu W, Federico L, Naples M, Avramoglu-Kohen R, Meshkani R, Zhang J, Tsai J, Kontos CD, Horie Y, Suzuki A, 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, Polansky MM, Sato Y, Adeli K, Anderson RA. Tumor necrosis factor-α Induces cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals. J Nutr Biochem. 2008; 294(5): G1120-9.

Hsieh J, Hayashi AA, Webb J, Adeli K. Postprandial dyslipidemia in insulin resistance: mechanisms and role of intestinal insulin sensitivity. Atherosclerosis Suppl. 2008 Sep;9(2):7-13.

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; 294(5): G1120-9.

Schnabl K, Chan MK, Gong Y, Adeli K. Closing the gaps in paediatric reference intervals: The CALIPER Initiative. Clin Biochem Rev. 2008;29(3):89-96. (Invited Review)

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.

Nelken J, Meshkani R, Chahal N, McCrindle B, Adeli K.  Detection of familial defective apoB (FDB) mutations in hypercholesterolemic children and adolescents by denaturing high performance liquid chromatography (DHPLC).  Clin Biochem.  2008 Apr; 41(6): 395-9.

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.

Nerurkar PV, Lee YK, Motosue M, Adeli K, Nerurkar VR.  Momordica charantia (bitter melon) reduces plasma apolopoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interations.  Br J Nutr. 2008 Oct;100(4):751-9.

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

Collins KL, Roberts EA, Adeli K, Bohn D, Harvey EA.  Single pass albumin dialysis (SPAD) in fulminant Wilsonian liver failure: a case report.  Pediatric Nephrol.  2008; 23(6):1013-6.

Kelishadi R, Hashemipour M, Mohammadifard N, Alikhassy H, Adeli K.  Short- and long-term relationships of serum ghrelin with changes in body composition and the metabolic syndrome in prepubescent obese children following two different weight loss programs.  Clin Endocrinol (Oxf).  2008; 69(5):721-9.

Engelhardt T, McCheyne AJ, Morton N, Karsli C, Luginbuehl I, Adeli K, Walsh W, Bissonnette B.  Clinical adaptation of a pharmacokinetic model of Propofol plasma concentrations in children.  Paediatr Anaesth.  2008 Mar:18(3):235-9.

Kelishadi R, Gouya MM, Adeli K, Ardalan G, Gheiratmand R, Majdzadeh R, Mahmoud-Arabi MS, Delavari A, Riazi MM, Barekati H, Motaghian M, Shariatinejad K, Heshmat R; for the CASPIAN Study Group. Factors associated with the metabolic syndrome in a national sample of youths: CASPIAN Study. Nutr Metab Cardiovasc Dis. 2008; 18(7):461-70.

2007

Qin B, Qiu W, Avramoglu-Kohen R, Adeli K. Tumor necrosis factor-α 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, 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.

Rutledge AC, Adeli K. Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms. Nutr Rev. 2007 Jun;65(6 Pt 2):S13-23. (Invited Review)

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.

Meshkani R, Taghikhani M, Mosapour A, Larijani B, Khatami S, Khoshbin E, Ahmadvand D, Saeidi P, Maleki A, Yavari K, Nasoohi N, Adeli K. 1484insG polymorphism of the PTPN1 gene is associated with insulin resistance in an Iranian population. Arch Med Res. 2007 Jul;38(5):556-62.

Kelishadi R, Badiee Z, Adeli K. Cord blood lipid profile and associated factors: baseline data of a birth cohort study. Paediatr Perinat Epidemiol. 2007 Nov;21(6):518-24.

Meshkani R, Taghikhani M, Larijani B, Bahrami Y, Khatami S, Khoshbin E, Ghaemi A, Sadeghi S, Mirkhani F, Molapour A, Adeli K. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population. Clin Chem Lab Med. 2007;45(4):477-82.

McCrindle BW, McIntyre S, Kim C, Lin T, Adeli K. Are patients after Kawasaki disease at increased risk for accelerated atherosclerosis? J Pediatr. 2007 Sep;151(3):244-8, 248.e1.

Sidiropoulos KG, Meshkani R, Avramoglu-Kohen R, Adeli K. Insulin inhibition of apolipoprotein B mRNA translation is mediated via the PI-3 kinase/mTOR signaling cascade but does not involve internal ribosomal entry site (IRES) initiation. Arch Biochem Biophys. 2007 Sep 15;465(2):380-8.

Sidiropoulos KG, Zastepa A, Adeli K. Translational control of apolipoprotein B mRNA via insulin and the protein kinase C signaling cascades: evidence for modulation of RNA-protein interactions at the 5'UTR. Arch Biochem Biophys. 2007 Mar 1;459(1):10-9.

Kelishadi R, Ardalan G, Adeli K, Motaghian M, Majdzadeh R, Mahmood-Arabi MS, Delavari A, Riazi MM, Namazi R, Ramezani MA; CASPIAN Study Group. Factor analysis of cardiovascular risk clustering in pediatric metabolic syndrome: CASPIAN study. Ann Nutr Metab. 2007;51(3):208-15.

Kelishadi R, Gheiratmand R, Ardalan G, Adeli K, Mehdi Gouya M, Mohammad Razaghi E, Majdzadeh R, Delavari A, Shariatinejad K, Motaghian M, Heshmat R, Heidarzadeh A, Barekati H, Sadat Mahmoud-Arabi M, Mehdi Riazi M; for the CASPIAN Study Group. Association of anthropometric indices with cardiovascular disease risk factors among children and adolescents: CASPIAN Study. Int J Cardiol. 2007 May 2;117(3):340-8.

2006

Kelishadi R, Ardalan G, Gheiratmand R, Adeli K, Delavari A, Majdzadeh R, For The Caspian Study Group. Paediatric metabolic syndrome and associated anthropometric indices: the CASPIAN Study. Acta Paediatr. Acta Paediatr. 2006 Dec;95(12):1625-34.

Federico L, Xia Z, Naples M, Taylor D, 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.

Mansoub S, Chan MK, Adeli K. Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome. Clin Biochem. 2006 Jun;39(6):569-87.

Avramoglu-Kohen R, Basciano H, Adeli K. Lipid and lipoprotein metabolism in insulin resistant states. Clin. Chim. Acta 2006, 368(1-2):1-19.

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.

Sarkissian T, Beyenne J, Feldman B, Adeli K, Silverman E. The complex nature of the interaction between disease activity and therapy on the lipid profile in patients with pediatric systemic lupus erythematosus. Arthritis Rheum. 2006 Apr;54(4):1283-90.

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.

Yip P, Chan M-K, Zielinski N, Adeli K. Heparin interference in whole blood sodium measurements in a pediatric setting. Clin Biochem. 2006 39(4):391-5.

Meshkani R, Taghikhani M, Larijani B, Khatami S, Khoshbin E, Adeli K. The relationship between homeostasis model assessment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance. Clin Chim Acta. 2006 May 19 [Epub ahead of print]

Li RW, Douglas TD, Maiyoh GK, Adeli K, Theriault AG. Green tea leaf extract improves lipid and glucose homeostasis in a fructose-fed insulin-resistant hamster model. J Ethnopharmacol. 2006 Mar 8;104(1-2):24-31.