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Pathogenesis of obesity

Author
George A Bray, MD
Section Editor
F Xavier Pi-Sunyer, MD, MPH
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Obesity has many causes, each of which has a variable genetic component [1-4]. At one extreme are the kinds of obesity caused by single-gene mutations. At the other extreme are the kinds of obesity caused by various diseases (such as damage to the ventromedial hypothalamus) in subjects in whom obesity would otherwise not occur [1].

This topic will review the types of obesity caused by single gene defects, the genetic susceptibility to obesity, and the pathogenetic mechanisms that operate within this genetic framework to cause differences in total body fat content and in regional fat distribution.

Other factors associated with the development of obesity, such as diet, lifestyle, drugs, and endocrine disorders, are discussed elsewhere.

GENETIC FACTORS

Studies of twins, adoptees, and families all suggest the existence of genetic factors in humans with obesity [5,6]. The heritability of obesity estimated from twin studies is high, ranging between 0.6 and 0.9, with only slightly lower values in twins raised apart compared with those raised together. Similarly, in adoptees the body mass index (BMI) correlates with that of their biologic parents rather than that of their adoptive parents.

In addition to the heritability of weight, metabolic rate, thermic response to food, and spontaneous physical activity are to a variable degree heritable [6]. With respect to body weight, percentage of fat, fat mass, and estimated subcutaneous fat, there was approximately three times more variance among pairs than within pairs. Thus, both current weight status and the metabolic processes underlying weight gain have a strong inherited component.

                             

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Literature review current through: Nov 2016. | This topic last updated: Mon Aug 29 00:00:00 GMT+00:00 2016.
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