Research

Figure showing the mechanisms of dyslipidemia
Figure showing how GLP-1 and GLP-2 act as hormones to exert effects on multiple organs through central and peripheral signaling
Figure showing the role of microbiota in host lipoprotein metabolism

Fundamental Research

Insulin-resistant states, such as obesity, metabolic syndrome, and type 2 diabetes, have become a global epidemic in both children and adults. They represent major risk factors for atherosclerotic cardiovascular disease, largely due to lipid and lipoprotein abnormalities. The key mechanism underlying this metabolic dyslipidemia is hepatic and intestinal overproduction of atherogenic lipoproteins. The focus of our basic research program is to understand the cellular, molecular, and physiological regulation of intestinal chylomicron and hepatic lipoprotein production in normal and insulin resistant states.

The Adeli Lab was first to demonstrate hepatic and intestinal lipoprotein overproduction and the novel role of gut hormones (GLP-1 and GLP-2) in an insulin resistant hamster model. These observations have now been confirmed in humans. Most recently, we have discovered and reported a complex gut-brain-liver axis (via vagal and CNS receptors) that is triggered upon fat ingestion to modulate lipid and lipoprotein metabolism in healthy and diabetic states.

Our current fundamental research activities:

  • Investigating the neuroendocrine and molecular mechanisms that control dietary fat absorption and lead to chylomicron overproduction and diabetic dyslipidemia in insulin resistant states.

  • Investigating the physiological and pathophysiological mechanisms underlying regulation of dietary fat absorption in the intestine and production of chylomicrons by gut hormones (GLP-1 and GLP-2) in metabolic health and disease. Recently, we found that Neuronal Nitric Oxide (nNOS) appears to mediate GLP-2 regulation of dietary fat absorption and metabolism. Studies in the hamster and nNOS knockout mice clearly support the hypothesis that intestinal nNOS is a key regulator of lipid metabolism.

  • Investigating the physiological and pathophysiological mechanisms underlying regulation of hepatic lipid metabolism and VLDL production by gut hormones (GLP-1 and GLP-2) in metabolic health and disease.

  • Developing and characterizing hamster knockout models, including GLP-1 receptor and GLP-2 receptor knockouts. The GLP-1 receptor knockout has been developed (in collaboration with Dr. Zhongde Wang at Utah State University) and is currently being characterized in our laboratory.

  • Investigating bile acid regulation of dietary fat absorption and intestinal chylomicron production. A TGR-5 (bile acid receptor) knockout hamster model has been developed and is being characterized to elucidate the signaling role of bile acids in lipid and lipoprotein metabolism.

  • Investigating the role of gut microbiota in controlling dietary fat absorption, intestinal lipoprotein production, as well as hepatic lipoprotein metabolism. Our recent preliminary data suggest a key role for gut microbiota in lipid metabolism. We have completed characterization of gut microbiota in the hamster model in the basal state as well as after a high-fat or high-fructose challenge. Antibiotic-induced inhibition of gut microbiota was found to have a marked effect on both circulating lipids (major reduction of plasma triglyceride) as well as hepatic lipid and lipoprotein secretion (marked reduction in hepatic VLDL levels).

  • Investigating the molecular and physiological mechanisms involved in serotonin regulation of intestinal lipid and lipoprotein homeostasis. We have found a very interesting link between serotonin synthesis in enterochromaffin cells of the intestine and the control of dietary fat absorption and metabolism.

Clinical Research

Dr. Adeli has been leading a national initiative to establish a comprehensive database of reference or “normal” ranges for medical laboratory tests in children and teens. Since 2009, the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has developed up-to-date reference intervals for hundreds of biomarkers on multiple analytical platforms, with the aim to facilitate interpretation of medical test results and improve the accuracy of medical decision-making in paediatric patients. The CALIPER database can be accessed online or via our mobile app available on the App Store or Google Play Store. As the CALIPER project grows and develops, the database is updated with new tests. In addition to new tests, the CALIPER project continues to investigate the influence of age, sex, ethnicity, body mass index (BMI), and other factors on biomarker levels.

Our current clinical research activities:

  • Establishment of age- and sex-specific reference intervals for blood tests in healthy children and adolescents. We continue to establish accurate paediatric reference intervals for all routine and specialized biomarkers of health and disease (including biochemical, immunological, and hematological markers) on many different laboratory testing systems. This ensures that all laboratories have access to robust reference intervals regardless of the type of instrument used to test children and adolescents.

  • Mother & Child Health Initiative. The CALIPER Mother & Child Study has recently been initiated to establish accurate reference intervals to interpret laboratory test results in healthy pregnant women and make appropriate clinical decisions for both mother and infant.

  • Early Childhood Study. This study aims to develop more accurate reference intervals for children under 5 years of age.

  • COVID-19 Study. We have embarked on a new study to help determine the rate of past and present SARS-CoV-2 infection in children and adolescents in the Greater Toronto Area (GTA).

  • Lipid Metabolism in Adolescents Study. In this study, we are examining changes in lipid metabolism among children and adolescents with insulin resistance and obesity, which will provide a better understanding of the link between type 2 diabetes and heart disease.

  • Harmonization of reference intervals. As part of the Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization, we are leading and coordinating a study to harmonize laboratory reference intervals for biochemical markers across Canadian clinical laboratories. There is huge variation in what laboratories use as reference standards, which leads to significant variation in test result interpretation and diagnostic errors.

To learn more about the CALIPER project and our ongoing research, please visit the CALIPER website, Facebook, or Twitter.

CALIPER logo with our slogan: 'ARM' us with the knowledge to help others
On the CALIPER mobile app, users can enter the medical lab test, test result, test unit, patient sex, patient age, and lab instrument (optional) to evaluate a test result.

Funding

Canadian Institutes of Health Research
Heart and Stroke Foundation of Canada
March of Dimes
Abbott Diagnostics
Beckman Coulter Diagnostics logo
DiaSorin
Roche Diagnostics
Siemens
Ortho Diagnostics