While the role of atherogenic low-density lipoproteins (LDL) is well established in cardiovascular disease, their role in type 2 diabetes (T2D) has just been recently recognized. Clinical evidence from our lab first established that elevated numbers of LDL, measured as plasma apoB, predict risk factors for T2D in humans. Epidemiological data also confirmed that hyperapoB predicts the incidence of T2D; however, underlying mechanisms remained unclear. We completed a clinical trial to test the hypothesis that subjects with high plasma apoB have upregulated innate immunity pathways in their white adipose tissue (WAT NLRP3 inflammasome/IL-1β pathway). We also tested the effect of 3-month supplementation with omega-3 (2.7 gm/day, EPA:DHA, 2:1, Webbers Naturals) on dampening this inflammatory pathway.
Forty non-diabetic adults were enrolled, and 33 subjects completed this trial. Our results indicate that subjects’ LDL upregulate IL-1β -secretion when incubated with their own hip WAT biopsies in culture. Corroborating that, subjects with high-apoB had higher WAT IL-1β-secretion than those with low-apoB independent of covariates. The association of WAT IL-1β-secretion with T2D risk factors was not pathogenic in all subjects but mostly in high-apoB subjects. Supplementation with EPA:DHA abolished group-differences in WAT IL-1β-secretion between subjects with low- versus high- apoB and reduced T2D risk factors. Confirming that, EPA:DHA inhibited WAT IL-1β-secretion induced by LDL in culture.
In conclusion, LDL upregulate the IL-1β-secretion in human WAT, which may explain higher diabetes risk in subjects with hyperapoB. We propose using EPA:DHA to target the IL-1β pathway and reduce the risk for T2D in humans.
(ClinicalTrials.gov NCT04496154)
Dr May Faraj obtained her BSc in Nutrition from the American University of Beirut, Lebanon. She then obtained an MSc in Nutrition in 1999 followed by a PhD in Experimental Medicine in 2003 from McGill University and became a member of “L’Ordre Professionnel des Diététistes du Québec”. She completed her postdoctoral fellowship at the department of Nutrition, Université de Montréal, where she later acquired her first academic position in 2008.
Dr Faraj is currently a professor of Nutrition at university of Montreal, an adjunct professor at the Division of Experimental Medicine at McGill University and the director of the Laboratory of Nutrition, Lipoproteins and Cardiometabolic Disease at Montreal Clinical Research Institute. Her research unit and team have been continuously supported by Canadian Foundation for Innovation, Canadian Institute of Health Research and Fonds de recherche du Québec (FRQ).
Dr Faraj’s lab initiated the field of research examining how elevated atherogenic lipoproteins are a promoter and not a mere consequence of diabetes in humans. Her lab also investigates how nutritional interventions may be used to target underlying mechanisms and reduce the risk for diabetes. To date, her team ran 3 clinical trials in this field, the results of which were communicated in 111 published manuscripts and abstracts and presented in multiple conferences. This work was made possible by a stellar team of 2 postdoctoral fellows, 6 PhDs, 13 MSc and 18 undergrads. The findings of an unpublished clinical trial with omega-3 supplementation will be presented here.