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This version published online on June 12, 2003
Endocrinology, doi:10.1210/en.2003-0373
A more recent version of this article appeared on September 1, 2003
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*Substance via MeSH
Medline Plus Health Information
*Nutrition
*Obesity

Submitted on March 25, 2003
Accepted on May 13, 2003

HUMAN OBESITY: LESSONS FROM MONOGENIC DISORDERS

Stephen O'Rahilly1*, I. Sadaf Farooqi1, Giles S.H. Yeo1, and Benjamin G. Challis1

1 From The University Departments Of Medicine And Clinical Biochemistry, Cambridge Institute Of Medical Research, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK

* To whom correspondence should be addressed. E-mail: sorahill{at}hgmp.mrc.ac.uk.

Genetic influences on the determination of human fat mass are profound and powerful, a statement which does not conflict with the obvious influence of environmental factors that drive recent changes in the prevalence of obesity. The assertion of the importance of genetic factors, has until recently, largely been based on twin and adoption studies. However, in the last six years, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually associated with disruption of normal appetite control mechanisms. Progress in the identification of more common, subtler genetic variants that influence fat mass in larger numbers of people has been slower, but discernible.

Human genetics will continue to make an invaluable contribution to the study of human obesity by identifying critical molecular components of the human energy balance regulatory systems, pointing the way toward more targeted and effective therapies and assisting the prediction of individual responses to environmental manipulations.




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