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A new class of obesity genes encodes leukocyte adhesion receptors
Z M Dong1, J C Gutierrez-Ramos, A Coxon
1Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin alphaMbeta2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity.
Insights
Defects in leukocyte adhesion molecules, such as intercellular adhesion molecule-1, can lead to obesity in mice. These findings suggest leukocytes regulate body fat and energy expenditure, impacting obesity development.
Area of Science:
- Immunology
- Genetics
- Metabolic Disease
Background:
- Obesity is a complex trait influenced by multiple genes.
- Previous research identified five genes linked to monogenic obesity in mice.
- The genetic basis of obesity requires further investigation into additional contributing genes.
Purpose of the Study:
- To identify novel genes regulating adipose tissue mass.
- To investigate the role of leukocyte adhesion molecules in obesity.
- To explore the connection between leukocyte function and lipid metabolism.
Main Methods:
- Genetic analysis of mice with deficiencies in specific adhesion molecules.
- Phenotypic characterization of obesity in genetically modified mice.
- Assessment of food intake and body composition.
Main Results:
- Mice lacking intercellular adhesion molecule-1 (ICAM-1) developed obesity.
- Mice lacking leukocyte integrin alphaMbeta2 (Mac-1) also exhibited obesity.
- Obesity occurred independently of increased food consumption, suggesting a role in metabolism or energy expenditure.
Conclusions:
- Leukocytes play a crucial role in preventing excessive body fat accumulation.
- Impaired leukocyte adhesion receptor function is linked to obesity development.
- Adhesion molecules represent potential targets for understanding and treating obesity.