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Ether lipids

Enzymes linked to diabetes and obesity appear to play key roles in arthritis and leukemia, potentially opening up new avenues for treating these diverse diseases, according to researchers at Washington University School of Medicine in St. Louis.

A STRUCTURE IN CELLS THAT MAKES KEY ENZYMES PREVIOUSLY LINKED TO DIABETES AND OBESITY, ALSO APPEARS TO BE IMPORTANT IN SEEMINGLY UNRELATED DISORDERS, SUCH AS ARTHRITIS AND LEUKEMIA. AND ENDOCRINOLOGY RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS SAY THE DISCOVERY COULD LEAD TO MORE EFFECTIVE TREATMENTS FOR THOSE PROBLEMS. JIM DRYDEN REPORTS…

THE RESEARCHERS WERE WORKING WITH GENETICALLY ENGINEERED MICE THAT DIDN’T MAKE CERTAIN ENZYMES, SUCH AS FATTY ACID SYNTHASE. AND THEY FOUND THAT WITHOUT THAT ENZYME, A PART OF THE CELL CALLED THE PEROXISOME WASN’T ABLE TO MAKE A SPECIAL TYPE OF LIPID, CALLED AN ETHER LIPID. FIRST AUTHOR IRFAN LODHI IS A WASHINGTON UNIVERSITY ENDOCRINOLOGY RESEARCHER.

(act) :19 o/c in neutrophils

Our study suggests that peroxisomes synthesize a special

class of lipids, called ether lipids. When we inactivated an enzyme called fatty acid synthase, ether lipids were reduced,

and there was a selective and dramatic reduction in neutrophils.

LODHI, AND COLLEAGUE CLAY SEMENKOVICH, WERE SURPRISED THAT NEUTROPHILS WERE AFFECTED.

(act) :05 o/c for neutrophils

The finding, I think, is truly surprising because of its

selectivity for neutrophils.

SEMENKOVICH SAYS NO OTHER CELLS SEEMED TO BE AFFECTED WHEN CELLS IN THE MICE COULDN’T MAKE ETHER LIPIDS. AND HE SAYS SINCE THOSE SPECIAL ETHER LIPIDS ARE MADE ONLY IN THE PART OF THE CELL CALLED THE PEROXISOME, THE FINDING PROVIDES A VERY SPECIFIC TARGET FOR BLOCKING ETHER LIPIDS, AND THUS, INFLUENCING THE NUMBER OF NEUTROPHILS IN THE SYSTEM.

(act) :19 o/c benefit health

When you actually, in a targeted way, specifically took

out ether lipids, you could also take out neutrophils. So

this is extending the paradigm of cells make lipids; they

make so in a very channeled and specific way; and by getting

more discreet about where you take out those lipids, you could

have very specific effects that could benefit health.

LIMITING THE POPULATION OF NEUTROPHILS COULD HELP PEOPLE WHO HAVE DISEASES WHERE NEUTROPHILS PLAY A BIG ROLE, SUCH AS RHEUMATOID ARTHRITIS AND LEUKEMIA. AND LODHI SAYS THAT ALTHOUGH LIMITING THE ABILITY OF CELLS TO MAKE ETHER LIPIDS GOT RID OF MATURE NEUTROPHILS, IT DIDN’T SEEM TO AFFECT THE PRODUCTION OF THOSE CELLS.

(act) :13 o/c mature neutrophils

It was a highly selective depletion of neutrophils, so

that was responsible for the low white blood cell count.

Differentiation of neutrophils from precursors was not

affected. It was the mature neutrophils.

AND SEMENKOVICH SAYS BY TARGETING ETHER LIPIDS, IT MAY BE POSSIBLE TO CONTROL THE NUMBERS OF NEUTROPHILS AND MAKE IT EASIER TREAT DISEASES LIKE ARTHRITIS AND LEUKEMIA.

(act) :13 o/c as well

So the “magic” will be to go far enough downstream

to find the perfect target that regulates inflammation

in a way that could treat, for example, leukemias, could treat

chronic inflammation, arthritis and potentially treat

obesity as well.

SEMENKOVICH AND LODHI REPORT THEIR FINDINGS IN THE JOURNAL CELL METABOLISM. I’M JIM DRYDEN…

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