Isolation and characterization of mutations that cause obesity and excessive feeding in Drosophila

Bader F. Al-Anzi, Seymour Benzer

There is a strong correlation between fat content and the ability of a fly to resist starvation. One, therefore, can select for mutant obese flies based on their ability to resist starvation. Potentially obese flies should survive while all others die, making it possible to screen thousands of mutagenized flies in a relatively short time. Approximately 22,000 mutagenized males were tested, out of which 36 males passed the first starvation trial and were used to establish mutant lines. To date, eight of those lines exhibit bona fide starvation resistance that is associated with an increase in their lipid content. Histological studies have also shown that this increase in the lipid content is associated with an increase in both fat cell size and number in those mutants as compared to wild type.

Many behavioral and metabolic abnormalities, such as excessive feeding, low activity level, and metabolic shift towards fatty acid synthesis, can cause obesity. We are using behavioral and biochemical assays to determine the underlying defects that are responsible for the obese mutant phenotypes. These include feeding rate, metabolic rate, level of activity, fat cell count, and level of de novo fatty acid synthesis.

The use of Drosophila in obesity research may help determine whether appetite and body weight regulation have underlying biological mechanisms that have been conserved throughout the Metazoa, as has been shown to be the case for genes that regulate such behavioral phenomena as learning and the circadian clock.