Abstract: Series 108, Lecture 6
The Harvey Lectures Series 108 (2012—2013)
previous lecture | next lecture
Lecture #6: Thursday, April 18, 2013 — Watch Video of Lecture
Human Obesity and Insulin Resistance:
Lessons from Extreme Phenotypes
Stephen O’Rahilly, MD
Professor of Clinical Biochemistry & Medicine
Co-Director, Metabolic Research Laboratories, Institute of Metabolic Science
Addenbrooke’s Hospital
University of Cambridge
Cambridge, United Kingdom
The genetic component of quantitative metabolic traits is complex with a mixture of common alleles of small effect and rarer alleles of larger effect. We have principally focused on finding the latter through the study of extreme human phenotypes of obesity and insulin resistance, including lipodystrophy. By applying both candidate and hypothesis-free genetic approaches we have identified multiple different genetic variants that cause highly penetrant forms of these diseases. Through detailed phenotypic studies in humans and relevant murine and cellular models, these disorders continue to provide new insights into the physiology and pathophysiology of energy balance and metabolism.