Obesity gene, mouse

Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J.M. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372 425 32. 

Also Y. Zhang, et al Positional cloning of the mouse obese gene and its homologue. Nature, ill, 425-432, 1994. 

Genetic Factors in Human Obesity Genetic Factors in Mouse Obesity Obese Gene and Leptin Summary of the t hysiotogy of Adipose Tissue gulation Diabetes Gene and the Lcpiin Receptor... 

Mouse on the right an obese mouse that does not produce leptin because of a genetic mutation in the leptin gene. Mouse in the middle a mouse that does not produce leptin but maintains relatively normal body weight because of its enhanced fat metabolism caused by the lack of perilipin. Mouse on the left a wild-type, normal mouse that produces leptin as well as perilipin. (Courtesy ofDrs. Lawrence Chan and Pradip Saha, Baylor College of Medicine.)... 

Figure 2.3 Researchers are currently studying laboratory rodents, like the mice in the upper photograph, to try to identify specific genes that may lead to obesity. The two mice shown are the same, except that the mouse on the left has had one gene removed. As you can see, the mouse on the left is thin, while the mouse on the right is obese. This leads researchers to believe that the gene removed may help cause obesity. By better understanding the causes of obesity, researchers will be better able to develop treatments for this condition in humans.

Neuropeptides play key roles in appetite regulation and obesity. Many genes for neuropeptides and neuropeptide receptors have been implicated in obesity and cachexia, anorexia and bulimia [34]. For example,NPY administration into the CNS causes overeating and obesity. A second peptide involved in obesity is leptin, a product of adipocytes and the stomach. The leptin gene is defective in the ob/ob mouse but in normal mice leptin binds to its receptor in the hypothalamus, causing a decrease in the synthesis and release of hypothalamic NPY. 

A second mouse gene, designated DB (diabetic), has also been found to have a role in appetite regulation. Mice with two defective copies (db/db) are obese and diabetic. The DB gene encodes the leptin receptor. When the leptin receptor is defective, the signaling function of leptin is lost. 

FIGURE 23-31 Obesity caused by defective leptin production. Both these mice, which are the same age, have defects in the OB gene. The mouse on the right was provided with purified leptin by daily injection, and weighs 35 g. The mouse on the left got no leptin, consequently ate more food and was less active, and weighs 67 g. 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

The importance of leptin to obesity is dramatically illustrated in mice. Mice lacking leptin are obese and will lose weight if given leptin. Mice that lack the leptin receptor are insensitive to leptin administration. Preliminary evidence indicates that leptin and its receptor play a role in human obesity, but the results are not as clear-cut as in the mouse. The interplay of genes and their products to control caloric homeostasis will be an exciting area of research for some time to come. 

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