EPFL BioE Talks SERIES "Circadian Timing of Glucose and Lipid Metabolism"
Event details
| Date | 15.03.2021 |
| Hour | 16:00 › 17:00 |
| Speaker | Prof. Charna Dibner, University of Geneva (CH) |
| Location | Online |
| Category | Conferences - Seminars |
WEEKLY EPFL BIOE TALKS SERIES
Abstract:
Circadian regulation of glucose and lipid metabolism has recently caught attention, but whether metabolite oscillations in peripheral organs are solely driven by diurnal cycles of rest/activity and food intake or are controlled in a cell autonomous manner, has not been assessed in humans. In this talk, I shall present our recent studies focusing on the molecular clocks operative in human α- and β-cells, and their role in temporal coordination of insulin and glucagon in physiological conditions, and in the context of type 2 diabetes. We found that islet cellular clocks are indispensable for temporal orchestration of the islet hormone secretion. These clocks are compromised in type 2 diabetic human islets, resulting to perturbed temporal secretion of insulin and glucagon. RORα agonist nobiletin boosting the disrupted clocks and insulin secretion in human islets from type 2 diabetic donors. To uncover the roles of the cell-autonomous clocks in the lipid homeostasis in human pancreatic islets we employed systematic mass spectrometry-based lipidomic analysis. Close to 10 % of the lipid metabolites from major lipid classes exhibited circadian oscillations in the human islets from non-diabetic donors cultured and synchronized in vitro. The observed oscillations in membrane lipids may indicate substantial remodeling of islet membranes on a daily basis. Furthermore, we demonstrated significant alterations of the lipid metabolite levels in human pancreatic islets associated with T2D, employing the same approach. Observed changes in the lipid homeostasis are likely indicative of an increase in the levels of inflammation and ER stress along with membrane saturation and rigidity. All together our findings suggest that disturbed circadian oscillators in human metabolic tissues might be implicated in type 2 diabetes development in humans. Defining tissue- and disease specific lipid signatures will have important diagnostic implications for personalized medicine. Furthermore, toxic lipid species accumulating upon metabolic diseases represent an important therapeutic target.
Bio:
Charna Dibner completed her PhD in Medical Sciences in 2002 under the supervision of Professor Dale Frank in the Department of Biochemistry at the Technion Israel Institute of Technology, headed by Nobel Laureate Professor Avram Hershko. She completed her postdoctoral studies in the Department of Molecular Biology at University of Geneva, with Professor Ueli Schibler, working on the mechanisms of transcriptional and temperature compensation of the mammalian circadian clocks. In 2009, she was appointed as a Group Leader of the Laboratory of Circadian Endocrinology in the Division of Endocrinology, Diabetes, and Nutrition, at the Faculty of Medicine, University of Geneva. In 2016 Charna was appointed as MER, and from February 2021 as an Associate Professor at the Faculty of Medicine, University of Geneva. Charna’s work centers upon the implication of circadian oscillators in regulation of metabolic processes in mammals. In particular, she is interested in unraveling the roles of the peripheral clocks in human metabolic diseases and cancer. Charna's work has been awarded with a number of prestigious Swiss prizes including Roche Research Foundation prize, Takeda prize for diabetes research, the awards by French Swiss Foundation of Diabetes Research, and by Leenaards prize of Lemanic (French Swiss) area 2019.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
Abstract:
Circadian regulation of glucose and lipid metabolism has recently caught attention, but whether metabolite oscillations in peripheral organs are solely driven by diurnal cycles of rest/activity and food intake or are controlled in a cell autonomous manner, has not been assessed in humans. In this talk, I shall present our recent studies focusing on the molecular clocks operative in human α- and β-cells, and their role in temporal coordination of insulin and glucagon in physiological conditions, and in the context of type 2 diabetes. We found that islet cellular clocks are indispensable for temporal orchestration of the islet hormone secretion. These clocks are compromised in type 2 diabetic human islets, resulting to perturbed temporal secretion of insulin and glucagon. RORα agonist nobiletin boosting the disrupted clocks and insulin secretion in human islets from type 2 diabetic donors. To uncover the roles of the cell-autonomous clocks in the lipid homeostasis in human pancreatic islets we employed systematic mass spectrometry-based lipidomic analysis. Close to 10 % of the lipid metabolites from major lipid classes exhibited circadian oscillations in the human islets from non-diabetic donors cultured and synchronized in vitro. The observed oscillations in membrane lipids may indicate substantial remodeling of islet membranes on a daily basis. Furthermore, we demonstrated significant alterations of the lipid metabolite levels in human pancreatic islets associated with T2D, employing the same approach. Observed changes in the lipid homeostasis are likely indicative of an increase in the levels of inflammation and ER stress along with membrane saturation and rigidity. All together our findings suggest that disturbed circadian oscillators in human metabolic tissues might be implicated in type 2 diabetes development in humans. Defining tissue- and disease specific lipid signatures will have important diagnostic implications for personalized medicine. Furthermore, toxic lipid species accumulating upon metabolic diseases represent an important therapeutic target.
Bio:
Charna Dibner completed her PhD in Medical Sciences in 2002 under the supervision of Professor Dale Frank in the Department of Biochemistry at the Technion Israel Institute of Technology, headed by Nobel Laureate Professor Avram Hershko. She completed her postdoctoral studies in the Department of Molecular Biology at University of Geneva, with Professor Ueli Schibler, working on the mechanisms of transcriptional and temperature compensation of the mammalian circadian clocks. In 2009, she was appointed as a Group Leader of the Laboratory of Circadian Endocrinology in the Division of Endocrinology, Diabetes, and Nutrition, at the Faculty of Medicine, University of Geneva. In 2016 Charna was appointed as MER, and from February 2021 as an Associate Professor at the Faculty of Medicine, University of Geneva. Charna’s work centers upon the implication of circadian oscillators in regulation of metabolic processes in mammals. In particular, she is interested in unraveling the roles of the peripheral clocks in human metabolic diseases and cancer. Charna's work has been awarded with a number of prestigious Swiss prizes including Roche Research Foundation prize, Takeda prize for diabetes research, the awards by French Swiss Foundation of Diabetes Research, and by Leenaards prize of Lemanic (French Swiss) area 2019.
Zoom link (with registration) for attending remotely: https://go.epfl.ch/EPFLBioETalks
IMPORTANT NOTICE: due to restrictions resulting from the ongoing Covid-19 pandemic, this seminar can be followed via Zoom web-streaming only, (following prior one-time registration through the link above).
Practical information
- Informed public
- Registration required
Organizer
- Prof. Giovanni D'Angelo, EPFL
Contact
- Institute of Bioengineering (IBI), Dietrich REINHARD