UT Southwestern researchers find leptin turns fat-storing cells into fat-burning cells.

http://www8.utsouthwestern.edu/utsw/...es/149526.html

UT Southwestern researchers find leptin turns
fat-storing cells into fat-burning cells

DALLAS - Feb. 9, 2004 - Increasing leptin, a protein involved in
regulating body weight, in laboratory animals transforms fat-storing cells
into unique fat-burning cells, researchers at UT Southwestern Medical Center
at Dallas report. They speculate that these findings could provide "a quick
and safe solution" to the obesity problem in humans.

Dr. Roger Unger, director of the Touchstone Center for
Diabetes Research at UT Southwestern, has found that increasing leptin in
laboratory animals converts fat-storing cells into fat-burning cells.
Researchers attribute the change in the cell's structure and
function in rats - from fat storing to fat-burning - to a massive increase
in the action of mitochondria, the principal energy source of the cell. The
increase in mitochondria, which also led to substantial weight loss in the
rats, was found two weeks after researchers injected the leptin gene.

Findings from the study will appear in an upcoming issue of the
Proceedings of the National Academy of Sciences and are currently available
online.

"This is the first careful examination of the fat cells after
leptin therapy," said Dr. Roger Unger, director of the Touchstone Center for
Diabetes Research at UT Southwestern, a physician at the Dallas Veterans
Affairs Medical Center and the study's senior author. "The structure of the
cells changed from the normal appearance of a fat cell to a very novel cell
that's really never been seen before. There's no precedent for a cell that
appears like this.

"The ability to convert fat cells into fat-burning cells may
suggest novel therapeutic strategies for obesity."

Dr. Unger and his collaborators began working on this research
in 1996. During the initial phase of the study, Dr. Unger observed that the
fat had disappeared in the fat cells, but at that time the researchers could
only guess why.

"We predicted this in 1996, but until we showed the increase in
mitochondria there was not any proof of what was happening, but there were
many clues that the fat was being burned inside the cell," Dr. Unger said.

Collaborating with researchers at the University of Geneva
Medical School, who conducted morphological tests to analyze the form and
structure of the cells, the scientists found in the current study that
instead of containing fat, the cells were crowded with mitochondria.

Researchers examined laboratory animals weighing between 280
grams (a little more than half a pound) and 300 grams. Some of the study
subjects received an intravenous injection of the leptin gene, which was
expressed in and produced by the liver; leptin level rose 50 times greater
than normal in rats after two to four days before tapering off. The
remaining laboratory animals followed a restricted diet.

Animals receiving the injection experienced a rapid and profound
loss of fat compared to the animals that followed a restricted diet.

"After 14 days, rats receiving leptin injections plummeted on
average from 280 to 207 grams," Dr. Unger said, or about 26 percent of total
body weight.

While the rats receiving the leptin injections were healthy,
active and had a decreased appetite, the animals that followed a restricted
diet were constantly searching for food and experienced reduced physical
activity.

The animals fed a restricted diet also gained back their weight
faster than animals receiving the leptin injections.

Under normal circumstances leptin produced by fat cells does not
interfere with the accumulation of surplus fat, but leptin secreted by the
liver does interfere with the fat and actually causes the surplus to burn
up, Dr. Unger said.

"We would like to break down the normal defense system against
leptin produced in the fat cell. If we could disable or bypass this system
and transform fat (storing) cells into fat-burning cells, then we may be a
step closer to solving the obesity epidemic."

Other UT Southwestern researchers who contributed to the study
were Dr. William Cook, a postdoctoral researcher in surgery; Dr. Byung-Hyun
Park, a postdoctoral researcher in internal medicine; and Dr. May-Yun Wang,
an instructor of internal medicine.

The study was funded by the National Institute of Diabetes and
Digestive and Kidney Diseases and the Swiss National Science Foundation.

###

Media Contact: Amy Shields
214-648-3404


--
Ken

"I want to tell you about a school in Houston. It's a school for 'at risk'
children.
In other words, folks, these are children who can't learn."

- G.W. Bush, presidential debates

Ken Kubos quoted:

http://www8.utsouthwestern.edu/utsw/...es/149526.html

UT Southwestern researchers find leptin turns
fat-storing cells into fat-burning cells

Animals receiving the injection experienced a rapid and profound
loss of fat compared to the animals that followed a restricted diet.

"After 14 days, rats receiving leptin injections plummeted on
average from 280 to 207 grams," Dr. Unger said, or about 26 percent of total
body weight.

The fun question isn't when injections will be available for humans.
The fun question is what dietary process causes human leptin levels
to go up or down.

Under normal circumstances leptin produced by fat cells does not
interfere with the accumulation of surplus fat, but leptin secreted by the
liver does interfere with the fat and actually causes the surplus to burn
up, Dr. Unger said.

This is interesting and it ties into other studies I've seen. Two
sources of leptin. High leptin levels suppress appetite (except that
high carb insulin swings override it and people get fat). Leptin
made by stored fat should drive the metabolism up (except the high
carb problem). That's why folks with 100+ to lose don't stall as
often from staying at 20; their leptin levels overwhelm other controls.
It's also why the last 10 are hard; no leptin to drive the fire.

But there's also leptin produced in the liver as well. Perhaps this is
the "leptin reset" leptin.

"We would like to break down the normal defense system against
leptin produced in the fat cell. If we could disable or bypass this system
and transform fat (storing) cells into fat-burning cells, then we may be a
step closer to solving the obesity epidemic."

A magic bullet. Folks will use it in droves. And need to continue
using it forever. Magic for the supplier as well as the user.