Sci­en­tists find out how key obe­sity gene works


Sci­en­tists have fi­nally fig­ured out how the key gene tied to obe­sity makes peo­ple fat, a ma­jor dis­cov­ery that could open the door to an en­tirely new ap­proach to the prob­lem be­yond diet and ex­er­cise.

The work solves a big mys­tery: Since 2007, re­searchers have known that a gene called FTO was re­lated to obe­sity, but they didn’t know how, and could not tie it to ap­petite or other known fac­tors.

Now ex­per­i­ments re­veal that a faulty ver­sion of the gene causes energy from food to be stored as fat rather than burned. Ge­netic tin­ker­ing in mice and on hu­man cells in the lab sug­gests this can be re­versed, giv­ing hope that a drug or other treat­ment might be de­vel­oped to do the same in peo­ple.

The work was led by sci­en­tists at MIT and Har­vard Univer­sity and pub­lished online Wed­nes­day by the New Eng­land Jour­nal of Medicine.

The dis­cov­ery chal­lenges the no­tion that “when peo­ple get obese it was ba­si­cally their own choice be­cause they choose to eat too much or not ex­er­cise,” said study leader Melina Clauss­nitzer, a ge­net­ics spe­cial­ist at Har­vard-af­fil­i­ated Beth Is- rael Dea­coness Med­i­cal Cen­ter. “For the first time, ge­net­ics has re­vealed a mech­a­nism in obe­sity that was not re­ally sus­pected be­fore” and gives a third ex­pla­na­tion or fac­tor that’s in­volved.

Sev­eral obe­sity drugs are al­ready on the mar­ket, but they are gen­er­ally used for short-term weight loss and are aimed at the brain and ap­petite; they don’t di­rectly tar­get me­tab­o­lism.

Re­searchers can’t guess how long it might take be­fore a drug based on the new find­ings be­comes avail­able. But it’s un­likely it would be a magic pill that would en­able peo­ple to eat any­thing they want with­out pack­ing on the pounds. And tar­get­ing this fat path­way could af­fect other things, so a treat­ment would need rig­or­ous test­ing to prove safe and ef­fec­tive.

The gene glitch doesn’t ex­plain all obe­sity. It was found in 44 per­cent of Euro­peans but only 5 per­cent of blacks, so other genes clearly are at work, and food and ex­er­cise still mat­ter.

Hav­ing the glitch doesn’t des­tine you to be­come obese but may pre­dis­pose you to it. Peo­ple with two faulty copies of the gene (one from Mom and one from Dad) weighed an av­er­age of 7 pounds more than those with­out them. But some were ob­vi­ously a lot heav­ier than that, and even 7 pounds can be the dif­fer­ence be­tween a healthy and an un­healthy weight, said Mano­lis Kel­lis, a pro­fes­sor at MIT.

He and Clauss­nitzer are seek­ing a patent re­lated to the work. It was done on peo­ple in Europe, Swe­den and Nor­way, and funded by the Ger­man Re­search Cen­ter for En­vi­ron­men­tal Health and oth­ers, in­clud­ing the U.S. Na­tional In­sti­tutes of Health.

Obe­sity af­fects more than 500 mil­lion peo­ple world­wide and con­trib­utes to a host of dis­eases. In the U.S., about one-third of adults are obese and another one-third are more mod­estly over­weight.

The FTO gene turns out to in­flu­ence obe­sity in­di­rectly, as a master switch that af­fects two other genes that con­trol ther­mo­ge­n­e­sis, or burn­ing off energy. It’s long been known that brown or beige fatty tis­sue — the so-called “good fat” — burns calo­ries, while the more com­mon white fat stores them. The body con­stantly makes fat cells, and the two genes de­ter­mine whether they be­come brown or white ones.

In one experiment de­scribed in the med­i­cal jour­nal, re­searchers blocked the faulty gene’s ef­fect in mice and found they be­came 50 per- cent leaner than other mice de­spite eat­ing a high-fat diet, and burned more energy even when asleep.

In other tests on hu­man cells, block­ing the gene’s ef­fect in­creased energy burn­ing in fat cells. Edit­ing out the prob­lem gene in hu­man cells in the lab also re­stored nor­mal meta­bolic func­tion.

Re­searchers don’t know the im­pact of hav­ing just one faulty copy of the gene but think it has less of an ef­fect than hav­ing two copies.

Sev­eral com­pa­nies are try­ing to de­velop treat­ments to stim­u­late brown fat, and the new re­search sug­gests a novel ap­proach.

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