Researchers Identify New Target In Fight Against Obesity

The new target, a molecule called hVps34, is activated by aminoacids (nutrients) entering the cell. This molecule triggers theactivation of an enzyme, S6 Kinase 1 (S6K1), whose function UCresearchers linked last year to obesity and insulin resistance.

"Insulin and amino acids both play a critical role in growthand development," said lead author George Thomas, PhD, interim directorof UC's Genome Research Institute and Department of Genome Science."Both are responsible for 'driving' cell growth. Now we have found thatthey actually work through independent pathways to trigger a moleculethat turns on S6K1.

"Since we know S6K1 is linked to obesity and insulinresistance," he added, "learning that it can actually be turned on bymore than one pathway is important, because it represents a potentialtarget to regulate obesity."

The findings appear in the Sept. 19, 2005, online edition of Proceedings of the National Academies of Sciences (PNAS).

In 2004, Dr. Thomas led research that identified S6K1'sfunction. Normally turned on through a series of reactions initiated bythe presence of insulin, it works to drive growth. But it also has asecond regulatory function.

When an organism "overfeeds," S6K1 becomes hyperactive,essentially telling insulin to stop bringing more nutrients into thecell. This hyperactive regulation actually results in insulinresistance.

"It would make sense then," said Dr. Thomas, "that once S6K1tells insulin to stop working, this enzyme would become inactive andits other function of promoting growth would also stop."

But in laboratory studies, Dr. Thomas and his team noticedthat mice on high-fat diets continued to grow, even after insulin quitperforming its normal function--indicating that S6K1 was still activeeven after it had seemingly sealed its own fate by shutting down thevery trigger that turns it on.

In single-cell organisms, said Dr. Thomas, feeding is theorganism's main concern. As multicelluar organisms arose, there becamea need to share nutrients within different cell types in order todevelop and grow. It i