Leptin, the appetite-suppressing obesity protein, is a word that hasn'tyet made its way into the medical dictionaries. But many leadingbiotechnology firms and pharmaceutical companies are counting onthe newly cloned and sequenced leptin molecule as forerunner of apossible _ perhaps probable _ treatment for the clinically obese,who make up 20 percent of the U. S. population. (See BioWorldToday, Feb. 12, 1996, p. 1.)

One such major player is Genentech Inc., of South San Francisco,which is testing its in-house recombinant leptin in obese breeds ofmice. Five of its scientists co-author a paper in today's Proceedingsof the National Academy of Sciences (PNAS) titled: "Decreased foodintake does not completely account for adiposity reduction after obprotein infusion."

Throughout industry and academia, two grossly overweight butgenetically dissimilar mouse strains are favored test models forresearching obesity. One is designated ob/ob, because it carriesmutant obesity genes from both parents, so produces no functionalleptin. The other, db/db, has inherited diabetes on both sides of itsfamily; it produces the ob protein, but fails to respond to its satietyfactor.

First author Nancy Levin, and her collaborators, report infusing theirrecombinant protein for 14 days into both rodent types, as well asinto normal lean mice.

On this regimen, animals of the ob/ob persuasion shed large amountsof body fat and weight, as well as eating less. Another group of ob/obmice, "pair-fed" exactly the same measured amount of food as thefirst group consumed voluntarily, lost less weight and fat.

The db/db mice, unable to metabolize the ob protein infusion theyreceived, added 7.8 percent to their initial obese body weight. Thiswas almost as much as the 9.7 percent put on by the gluttonouscontrol db/db animals infused only with saline solution.

ob/ob mice are genetically fated to go through life withhyperglycemia, hyperinsulinemia and hypercholesterolemia. The obprotein infusions lowered all three of these excessive levels to thehealthy values enjoyed by their lean control littermates.

In this lean ob/ob cohort, the PNAS paper reported, "ob proteininfusion significantly decreased body and fat-depot weights, whiledecreasing food intake to a much lesser extent than in ob/ob mice."This molecular mechanism, it observed, "remains to be elucidated."

In other words, leptin (the ob protein), did an even better job attrimming fat and slimming pounds than it did at curbing the murinemunchies. It's a somewhat different story in humans, the Genentechinvestigators observed. They cited recent evidence that in humanobesity, expression of the leptin gene is high, not low, implying thatits appetite-, weight- and fat-reducing functions are somehow lacking.Just how isn't known. (See BioWorld Today, Dec. 29, 1995, p. 1.) n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.