This network of genes triggers fat formation

Washington, April 9 : Scientists have gained fresh knowledge about how a network of genes triggers the conversion of cells into fat in a process called adipogenesis.

"We'd like to work our way back to the earliest events (that lead to fat formation). Eventually, we want to connect all the dots," said Jeffrey Friedman, a Howard Hughes Medical Institute Investigator at Rockefeller University.

Once knowledge about all the underlying events is gained, he adds, "we might intervene and alter fat development".

Scientists already knew that certain genes switch other genes on to control the adipogenesis, an insight they gained from previous studies.

Earlier studies had also shown that one of the earliest events pertaining to the process is the activation of a gene called C/EBP, though what turns on this gene remained uncovered.

Friedman's own group recently showed that a gene called Krox20 is active in early fat development and influences the expression of C/EBP, but the researchers were unable to show that it binds the DNA sequence that promotes C/EBP activity directly, suggesting that it does not "flip the switch" on its own.

The latest work by his team has now implicated another gene called Kr¼ppel-like factor 4 (KLF4) in the process.

The researchers have found that treatments that block KLF4 inhibit fat production, and yield lower C/EBP levels.

They have uncovered evidence that KLF4 physically binds to the previously discovered factor Krox20, and then binds directly to the C/EBP promoter to drive fat production.

In their study report, appearing in the journal Cell Metabolism, the researchers identify KLF4 as "an essential player in adipocyte differentiation".

"Our findings place KLF4 among a group of key proadipogenic early transcription factors," they write.

The researchers note that studies of KLF4 function in living animals will be necessary to evaluate the precise roles of these genes in fat development, and to determine whether there is redundancy in the positions held by various players in the process.

ANI