Khosrow Adeli

Khosrow Adeli PhD, FCACB, FACB, DABCC
Vice Chair, Quality
Professor
Department of Laboratory Medicine & Pathobiology
Khosrow Adeli
Contact Info
T: (416) 813-8682
F: (416) 813-6257
Website
Location
Hospital for Sick Children (SickKids)
555 University Ave.
Div of Clin Biochem, Rm 3653
Toronto, ON, M5G 1X8
Appointment Status Primary
Clinical Interests
Clinical Chemistry
Research Interests
Cardiovascular, Metabolism & Nutrition

Dr. Adeli has been actively involved in both basic and clinical laboratory research since 1988 and has published over 200 articles and abstracts to date.

His basic research program is focused on the link between insulin resistant diabetes and dysregulation of lipoprotein metabolism.

His group has been elucidating the molecular mechanisms linking diet-induced insulin resistance and metabolic dyslipidemia. His laboratory is employing animal models of insulin resistance to investigate the molecular mechanisms mediating the diabetogenic effect of fructose-rich diets, mechanisms of fructose-induced hepatic insulin resistance, and pathways leading to hepatic and intestinal lipogenesis and lipoprotein dysregulation.

Dr. Adeli has also been spearheading a national initiative in collaboration with other pediatric health centres across Canada to establish a comprehensive database of pediatric reference intervals for laboratory biomarkers of pediatric disease.

The new database will improve the clinical assessment, diagnosis, and monitoring of children and adolescents presenting with various medical concerns. The database has already been partially established and is available on the CALIPER project website as well as via a smartphone application on the Apple Store.

The Adeli Laboratory at the Hospital for Sick Children is employing animal models of insulin resistance to investigate the molecular mechanisms mediating the diabetogenic effect of fructose-rich diets, mechanisms of fructose-induced hepatic insulin resistance, and pathways leading to hepatic and intestinal lipogenesis and lipoprotein dysregulation.

Research/Teaching

Research Synopsis

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 pediatric 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 and Awards

View PubMed search of this faculty member's recent publications.

Recent Publications

Farr S, Baker C, Naples M, Taher J, Iqbal J, Hussain M, Adeli K. Central Nervous System Regulation of Intestinal Lipoprotein Metabolism by Glucagon-Like Peptide-1 via a Brain-Gut Axis. Arterioscler Thromb Vasc Biol. 2015 May;35(5):1092-100.

Devgun MS, Chan MK, El-Nujumi AM, Abara R, Armbruster D, Adeli K. Clinical decision limits for interpretation of direct bilirubin - A CALIPER study of healthy multiethnic children and case report reviews. Clin Biochem. 2015 Jan 1;48(1-2):93-96.

Markle JG, Frank DN, Adeli K, von Bergen M, Danska JS. Microbiome manipulation modifies sex-specific risk for autoimmunity. Gut Microbes. 2014 Jul 9;5(4).

Su Q, Baker C, Christian P, Naples M, Tong X, Zhang K, Santha M, Adeli K. Hepatic mitochondrial and ER stress induced by defective PPARα signaling in the pathogenesis of hepatic steatosis. Am J Physiol Endocrinol Metab. 2014 Jun 1;306(11):E1264-73.

Adeli K. Closing the gaps in pediatric reference intervals: The CALIPER project - An update. Clin Biochem. 2014 May 21.

Farr S, Taher J, Adeli K. Glucagon-Like Peptide-1 as a Key Regulator of Lipid and Lipoprotein Metabolism in Fasting and Postprandial States. Cardiovasc Hematol Disord Drug Targets. 2014 May 5.

Raizman JE, Cohen AH, Teodoro-Morrison T, Wan B, Khun-Chen M, Wilkenson C, Bevilaqua V, Adeli K. Pediatric reference value distributions for vitamins A and E in the CALIPER cohort and establishment of age-stratified reference intervals. Clin Biochem. 2014 Apr 12.

McNamara PJ, Engelberts D, Finelli M, Adeli K, Kavanagh BP. Vasopressin Improves Survival Compared to Epinephrine in a Neonatal Piglet Model of Asphyxial Cardiac Arrest. Pediatr Res. 2014 Mar 10.

Neuman G, Nulman I, Adeli K, Koren G, Colantonio DA, Helldén A. Implications of serum creatinine measurements on GFR estimation and vancomycin dosing in children. J Clin Pharmacol. 2014 Mar 5.

Bailey D, Bevilacqua V, Colantonio DA, Pasic MD, Perumal N, Chan MK, Adeli K. Pediatric Within-Day Biological Variation and Quality Specifications for 38 Biochemical Markers in the CALIPER Cohort. Clin Chem. 2014 Mar 1;60(3):518-29.

Erek-Toprak A, Bingol-Ozakpinar O, Karaca Z, Cikrikcioglu MA, Hursitoglu M, Uras AR, Adeli K, Uras F. Association of plasma growth arrest-specific protein 6 (Gas6) concentrations with albuminuria in patients with type 2 diabetes. Ren Fail. 2014 Feb 11.

Kyriakopoulou L, Yazdanpanah M, Colantonio D, Adeli K. In reply. Clin Chem. 2014 Feb 1;60(2):419-23.

Shaw JL, Cohen A, Konforte D, Binesh-Marvasti T, Colantonio DA, Adeli K. Validity of establishing pediatric reference intervals based on hospital patient data: A comparison of the modified Hoffmann approach to CALIPER reference intervals obtained in healthy children. Clin Biochem. 2014 Feb 1;47(3):166-72.

Bailey D, Perumal N, Yazdanpanah M, Al Mahmud A, Baqui AH, Adeli K, Roth DE. Maternal-fetal-infant dynamics of the C3-epimer of 25-hydroxyvitamin D. Clin Biochem. 2014 Jan 22.

Sniderman AD, Qi Y, Ma CI, Wang RH, Naples M, Baker C, Zhang J, Adeli K, Kiss RS. Hepatic cholesterol homeostasis: is the low-density lipoprotein pathway a regulatory or a shunt pathway? Arterioscler Thromb Vasc Biol. 2013 Nov 1;33(11):2481-90.

Rutledge AC, Qiu W, Zhang R, Urade R, Adeli K. Role of cysteine-protease CGHC motifs of ER-60, a protein disulfide isomerase, in hepatic apolipoprotein B100 degradation. Arch Biochem Biophys. 2013 Sep 1;537(1):104-12.

Yazdanpanah M, Bailey D, Walsh W, Wan B, Adeli K. Analytical measurement of serum 25-OH-vitamin D₃, 25-OH-vitamin D₂ and their C3-epimers by LC-MS/MS in infant and pediatric specimens. Clin Biochem. 2013 Sep 1;46(13-14):1264-71. 2012 Dec 23. pii: S0009-9120(12)00703-5. doi: 10.1016/j.clinbiochem.2012.11.030.

Bailey D, Colantonio D, Kyriakopoulou L, Cohen AH, Chan MK, Armbruster D, Adeli K. Marked biological variance in endocrine and biochemical markers in childhood: establishment of pediatric reference intervals using healthy community children from the CALIPER cohort. Clin Chem. 2013 Sep 1;59(9):1393-405. 2013 May 1.

Estey MP, Cohen AH, Colantonio DA, Chan MK, Marvasti TB, Randell E, Delvin E, Cousineau J, Grey V, Greenway D, Meng QH, Jung B, Bhuiyan J, Seccombe D, Adeli K. CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort. Clin Biochem. 2013 Sep 1;46(13-14):1197-219. 2013 Apr 8. pii: S0009-9120(13)00114-8. doi: 10.1016/j.clinbiochem.2013.04.001.

Mokhtari RB, Kumar S, Islam SS, Yazdanpanah M, Adeli K, Cutz E, Yeger H. Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines. BMC Cancer. 2013 Aug 8;13:378.

Konforte D, Shea JL, Kyriakopoulou L, Colantonio D, Cohen AH, Shaw J, Bailey D, Chan MK, Armbruster D, Adeli K. Complex biological pattern of fertility hormones in children and adolescents: a study of healthy children from the CALIPER cohort and establishment of pediatric reference intervals. Clin Chem. 2013 Aug 1;59(8):1215-27. 2013 May 1.

Dekker MJ, Baker C, Naples M, Samsoondar J, Zhang R, Qiu W, Sacco J, Adeli K. Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction. Atherosclerosis. 2013 May 1;228(1):98-109. 2013 May;228(1):98-109. doi: 10.1016/j.atherosclerosis.2013.01.041. Epub 2013 Feb 10.

Kyriakopoulou L, Yazdanpanah M, Colantonio DA, Chan MK, Daly CH, Adeli K. A sensitive and rapid mass spectrometric method for the simultaneous measurement of eight steroid hormones and CALIPER pediatric reference intervals. Clin Biochem. 2013 May 1;46(7-8):642-51. 2013 May;46(7-8):642-51. doi: 10.1016/j.clinbiochem.2013.01.002. Epub 2013 Jan 18.

Lu J, Ji J, Meng H, Wang D, Jiang B, Liu L, Randell E, Adeli K, Meng QH. The protective effect and underlying mechanism of metformin on neointima formation in fructose-induced insulin resistant rats. Cardiovasc Diabetol. 2013 Apr 5;12:58. 2013 Apr 5;12:58. doi: 10.1186/1475-2840-12-58.

Christian P, Sacco J, Adeli K. Autophagy: Emerging roles in lipid homeostasis and metabolic control. Biochim Biophys Acta. 2013 Apr 1;1831(4):819-24. Epub 2012 Dec 26.

Bailey D, Veljkovic K, Yazdanpanah M and Adeli K. Analytical measurement and clinical relevance of vitamin D(3) C3-epimer. Clin Biochem. 2013 Feb 1. 2013 Feb;46(3):190-6. doi: 10.1016/j.clinbiochem.2012.10.037. Epub 2012 Nov 12.

Hein GJ, Baker C, Hsieh J, Farr S, Adeli K. GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states. Diabetes. 2013 Feb 1;62(2):373-81. 2013 Feb;62(2):373-81. doi: 10.2337/db12-0202. Epub 2012 Oct 1.

Shaw JL, Binesh Marvasti T, Colantonio D, Adeli K. Pediatric reference intervals: challenges and recent initiatives. Crit Rev Clin Lab Sci. 2013 Feb 1;50(2):37-50. 2013 May 8.

Pinkosky SL, Filippov S, Srivastava RA, Hanselman JC, Bradshaw CD, Hurley TR, Cramer CT, Spahr MA, Brant AF, Houghton JL, Baker C, Naples M, Adeli K, Newton RS. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J Lipid Res. 2013 Jan 1;54(1):134-51.

Hsieh J and Adeli K. Regulation of intestinal chylomicron production by glucagon-like peptides. Cardiovasc Hematol Disord Drug Targets. 2012 Dec. 2012 Dec;12(2):92-7.

Pasic MD, Colantonio DA, Chan MK, Venner AA, Brinc D, Adeli K. Influence of fasting and sample collection time on 38 biochemical markers in healthy children: a CALIPER substudy. Clin Biochem. 2012 Oct 1;45(15):1125-30. 2012 Oct;45(15):1125-30. doi: 10.1016/j.clinbiochem.2012.07.089. Epub 2012 Jul 20.

Sparks JD, Sparks CE and Adeli K. Selective hepatic insulin resistance, VLDL overproduction, and hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2012 Sep. 2012 Sep;32(9):2104-12. doi: 10.1161/ATVBAHA.111.241463. Epub 2012 Jul 12.

Brinc D, Chan MK, Venner AA, Pasic MD, Colantonio D, Kyriakopolou L and Adeli K. Long-term stability of biochemical markers in pediatric serum specimens stored at -80 degrees C: a CALIPER Substudy. Clin Biochem. 2012 Jul. 2012 Jul;45(10-11):816-26. doi: 10.1016/j.clinbiochem.2012.03.029. Epub 2012 Apr 5.

Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L, Tam J, Adeli K, Cummins CL, Connelly PW and Ng DS. Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice. J Biol Chem. 2012 Jun 8. 2012 Jun 8;287(24):20755-68. doi: 10.1074/jbc.M112.340919. Epub 2012 Apr 12.

Sacco J and Adeli K. MicroRNAs: emerging roles in lipid and lipoprotein metabolism. Curr Opin Lipidol. 2012 Jun. 2012 Jun;23(3):220-5. doi: 10.1097/MOL.0b013e3283534c9f.

Yue JT, Mighiu PI, Naples M, Adeli K and Lam TK. Glycine normalizes hepatic triglyceride-rich VLDL secretion by triggering the CNS in high-fat fed rats. Circ Res. 2012 May 11. 2012 May 11;110(10):1345-54. doi: 10.1161/CIRCRESAHA.112.268276. Epub 2012 Apr 3.

Naples M, Baker C, Lino M, Iqbal J, Hussain MM and Adeli K. Ezetimibe ameliorates intestinal chylomicron overproduction and improves glucose tolerance in a diet-induced hamster model of insulin resistance. Am J Physiol Gastrointest Liver Physiol. 2012 May 1. 2012 May 1;302(9):G1043-52. doi: 10.1152/ajpgi.00250.2011. Epub 2012 Feb 16.

Colantonio DA, Kyriakopoulou L, Chan MK, Daly CH, Brinc D, Venner AA, Pasic MD, Armbruster D and Adeli K. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem. 2012 May. 2012 May;58(5):854-68. doi: 10.1373/clinchem.2011.177741. Epub 2012 Feb 27.

Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, Ann DK, Anoopkumar-Dukie S, Aoki H, Apostolova N, Arancia G, Aris JP, Asanuma K, Asare NY, Ashida H, Askanas V, Askew DS, Auberger P, Baba M, Backues SK, Baehrecke EH, Bahr BA, Bai XY, Bailly Y, Baiocchi R, Baldini G, Balduini W, Ballabio A, Bamber BA, Bampton ET, Banhegyi G, Bartholomew CR, Bassham DC, Bast RC Jr, Batoko H, Bay BH, Beau I, Bechet DM, Begley TJ, Behl C, Behrends C, Bekri S, Bellaire B, Bendall LJ, Benetti L, Berliocchi L, Bernardi H, Bernassola F, Besteiro S, Bhatia-Kissova I, Bi X, Biard-Piechaczyk M, Blum JS, Boise LH, Bonaldo P, Boone DL, Bornhauser BC, Bortoluci KR, Bossis I, Bost F. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr. 2012 Apr;8(4):445-544.

Shi SY, Martin RG, Duncan RE, Choi D, Lu SY, Schroer SA, Cai EP, Luk CT, Hopperton KE, Domenichiello AF, Tang C, Naples M, Dekker MJ, Giacca A, Adeli K, Wagner KU, Bazinet RP and Woo M. Hepatocyte-specific deletion of Janus kinase 2 (JAK2) protects against diet-induced steatohepatitis and glucose intolerance. J Biol Chem. 2012 Mar 23. 2012 Mar 23;287(13):10277-88. doi: 10.1074/jbc.M111.317453. Epub 2012 Jan 24.

Farr S and Adeli K. Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states. Curr Opin Lipidol. 2012 Feb. 2012 Feb;23(1):56-61. doi: 10.1097/MOL.0b013e32834d68f0.

Kelishadi R, Poursafa P, de Ferranti SD, Schwandt P, Adeli K, Onat A, Gidding SS. Pediatric metabolic syndrome: from prevention to treatment. Cholesterol. 2012 Jan 1;2012:374168. 2012;2012:374168. doi: 10.1155/2012/374168. Epub 2012 Nov 11.

Wengle JG, Hamilton JK, Manlhiot C, Bradley TJ, Katzman DK, Sananes R, Adeli K, Birken CS, Abadilla AA and McCrindle BW. The ‘Golden Keys’ to health - a healthy lifestyle intervention with randomized individual mentorship for overweight and obesity in adolescents. Paediatr Child Health. 2011 Oct;16(8):473-8.

Adeli K. Closing the gaps in pediatric reference intervals: The CALIPER initiative. Clin Biochem. 2011: 44(7); 480-2.

Adeli K. Translational control mechanisms in metabolic regulation: Critical role of RNA binding proteins, miRNAs, and cytoplasmic RNA granules. Am J Physiol Endocrinol Metab. 2011: 301(6); E1051-64.

Karimian Pour N and Adeli K. Insulin silences apolipoprotein B mRNA translation by inducing intracellular traffic into cytoplasmic RNA graules. Biochemistry. 2011: 50(32); 6942-50.

Qiu W, Zhang J, Dekker MJ, Wang H, Huang J, Brumell JH, Adeli K. Hepatic autophagy mediates ER stress-induced degradation of misfolded apolipoprotein B. Hepatology. 2011: 53(5); 1515-25.

Wang H, Zhang J, Qiu W, Han GS, Carman GM, Adeli K. Lipin-1y isoform is a novel lipid droplet-associated protein highly expressed in the brain. FEBS Lett. 2011: 585(12); 1979-84.

Hayashi AA, Webb J, Choi J, Baker C, Lino M, Trigatti B, Trajcevski KE, Hawke TJ, Adeli K. Intestinal SR-BI is upregulated in insulin resistant states and is associated with overproduction of intestinal apoB48-containing lipoproteins. Am J Physiol Gastrointest Liver Physiol. 2011: 301(2); G326-37.

Xi L, Xiao C, Bandsma RH, Naples M, Adeli K, Lewis GF. C-reactive protein impairs hepatic insulin sensitivity and insulin signalling in rats: Role of mitogen-activated protein kinases. Hepatology. 2011: 53(1); 127-35.

Xiao C, Hsieh J, Adeli K, Lewis GF. Gut-liver interaction in triglyceride-rich lipoprotein metabolism. Am J Physiol Endocrinol Metab. 2011: 301(3); E429-46.

O’Gorman CS, Simoneau-Roy J, Pencharz Mb P, Adeli K, Hamilton J. Delayed ghrelin suppression following oral glucose tolerance test in children and adolescents with hypothalamic injury secondary to craniopharyngioma compared with obese controls. In J Pediatr Obes. 2011: 6(3-4); 285-8.

Boros CA, Bradley TJ, Cheung MM, Bargman JM, Russell JL, McCrindle BW, Adeli K, Hamilton J, Silverman ED. Early determinants of atherosclerosis in paediatric systemic lupus erythematosus. Clin Exp Rheumatol. 2011: 29(3); 575-81.

Warnakula S, Hsieh J, Adeli K, Hussain MM, Tso P, Proctor SD. New insights into how the intestine can regulate lipid homeostasis and impact vascular disease: Frontiers for new pharmaceutical therapies to lower cardiovascular disease risk. Can J Cardiol. 2011: 27(2); 183-91.

Wong DT, George K, Wilson J, Manlhiot C, McCrindle BW, Adeli K, Kantor PF. Effectiveness of serial increases in amino-terminal pro-B-type natriuetic Peptide levels to indicate the need for mechanical circulatory support in children with acute decompensated heart failure. Am J Cardiol. 2011: 107(4); 573-8.

Lu J, Randell E, Han Y, Adeli K, Krahn J, Meng QH. Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy. Clin Biochem. 2011: 44(4); 307-11.

Lu J, Zello GA, Randell E, Adeli K, Krahn J, Meng QH. Closing the anion gap: Contribution of d-lactate to diabetic ketoacidosis. Clin Chim Acta. 2011: 412(3-4); 286-91.

Mohammadtaghvaei N, Meshkani R, Taghikhani M, Larijani B, Adeli K. Palmitate enhances protein tyrosine phosphatise 1B (PTP1B) gene expression at transcriptional level in C2C12 skeletal muscle cells. Inflammation. 2011: 34(1); 43-8.

Hayes J, Forrest C, Walsh W, Petroz G, Adeli K, Bissonnett B. Continuous bupivacaine infusion post-iliac crest bone graft harvesting in pediatric cleft surgery: Role and comparison with ketorolac. Cleft Palate Craniofac J. 2011: 48(5); 532-7.