Gold-Rush forty-niners and U.S. army troops in the mid-19th centuryowed debts of gratitude to the Pima Indians of southern Arizona.These peaceable tribes farmed the Gila river valley, and sold grainand other food crops to the prospectors who passed through, and thesoldiers who manned the outpost forts. What's more, friendly Pimascouts guided the white men along paths that avoided the warlikeApaches.

But when white settlers moved into in Arizona territory after the CivilWar, they diverted those Gila river waters to irrigate their own crops,and the Pima people fell on hungry times. Eventually, the FederalBureau of Indian Affairs put them on reservations, and on welfare.

Eating the high-fat content of the government hand-out food, thePimas began to put on weight. Today, they number 10,000 or so, andrank among the most obese and diabetic people on the planet. Backin 1902, a health survey of North American Indians turned up onecase of diabetes mellitus.)

Molecular biologist Mark Rowe, who chairs the department of foodscience and nutrition at Brigham Young University, in Provo, Utah,explained the Pimas' predicament: "They were subjected to movingfrom their agrarian society to federal food programs, much higher infat than the diet they were accustomed to. That probably was a majortrigger in expressing a number of genes, which they had built up inyears past to withstand famine, and that turned into a seriousdetriment when they were exposed to too many kilocalories."

Low Metabolic Rate: Predictor Of Obesity

The rate at which the body burns up calories, Rowe explained toBioWorld Today, apart from physical exertion and food digestion iscalled the metabolic rate. "There is an inherited component tometabolic rate," he added. "It seems to be familial. And a lowmetabolic rate is a risk factor for weight gain and therefore obesity."

Obesity in turn, Rowe emphasized, "is a risk factor for diabetes andgall bladder disease, and joint and heart diseases, all of which afflictthe Pimas out of all proportion." The genes that govern metabolicrate reside in the cell's mitochondria, which control the body'senergy supply. They are inherited in non-Mendelian fashion solelyfrom the maternal parent.

"Mitochondrial DNA," Rowe pointed out, "codes for energy-ratedenzymes in the mitochondrion." He set out to find which type of thatDNA affected the resting metabolic rate.

Rowe and his associates have studied this obesity inheritance patternin 245 Pima Indians, to identify which genes confer excess weightgain, and which do not. "The American Indians were a nice sample todo," he continued, "because their mitochondrial DNA type has beenexplored for anthropological purposes."

Those studies aimed to determine the origins of Amerindians, andhow many migrations there were of those tribes from Central Asia,across the Bering land bridge into North and South America.

Rowe reported on April 10 to the Federation of American Societiesof Experimental Biology , meeting in Atlanta, on his Pima metabolicinquiry. "We sequenced 13 genes, 85 percent of the coding region inthe mitochondrial DNA in each of these types in the Pima, to seewhat the differences were that could be the actual gene difference thatcorrelates with a low metabolic rate, or a high one."

His group identified two statistically valid mutant gene differences,reflecting respectively high and low metabolic rates.

"It really relates to the efficiency of how the mitochondrionoperates," Rowe said. If the mitochondria operate very efficiently,then there's really very good conversion of the consumed energy tostored energy. If they are less efficient, some of the energy getsdissipated as heat, not stored as fat _ which is really what a personwould like if he would like to be thin.

"It makes a difference of about 40 kilocalories a day in theindividuals," Rowe reported, "which means that on the average if twoPima Indians ate exactly the same diet, the one with the gene markerfor the lower metabolic rate could gain as much as five pounds peryear." He added, "That of course, over a number of years, couldmount up quite a bit."

This raises the question: "Can you change the genes, or what is thepractical implication of this finding?" Answering his own question,Rowe observed, "The implication at this point is not that we have theability to change genes, but we do have the ability to give people whohave been identified with these markers genetically intelligentnutrition counseling."

He compares such advice to "what you would give an individual whohad a serious family history of heart disease. You would counsel him,and he would hopefully be concerned enough about his history tochange his dietary habits and adjust for his low metabolic rate."

Next: Check Out Antecedents In Central China

Rowe plans eventually, "now that mitochondrial genes definitely doplay a role in metabolic rate," to look at risk-factor markers inCaucasian populations. But first, "we're developing a project tocompare some people in Central China _ ancestors of our North andSouth American Indians _ who do and do not have those samegenes"

Clinical physiologist Richard Atkinson, a recent past president of theAmerican Society for the Study of Obesity, is professor of medicineand nutritional science at the University of Wisconsin in Madison."The genetic alternations in the mitochondria," he told BioWorld,"has implications for far more than just the Pima Indians.

"Most of the people on earth," he pointed out, "have very similarmitochondria. So the types of defects that occur in mitochondrialDNA have the potential to be very widespread. And as some of thosedefects favor the development of obesity, they could be modified insome fashion."

But Atkinson quickly added, "What Rowe is talking about obviouslyhas a long way to go before we're inserting genes in anybody. Butstill, the implications of it are absolutely enormous." He said thatRowe's presentation to the experimental biology meeting's obesitysession "was basic science at its best, with clear eventual clinicalrelevance; we need to do more of it." n

-- David N. Leff Science Editor

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

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