BUFFALO, N.Y. -- The adage "You are what you eat" should be
rephrased to include "and so are your children," based on metabolic
research pioneered by researchers at the University at Buffalo.
Previous studies by the UB scientists showed that rat pups
raised artificially on a high-carbohydrate milk formula identical
in calories to mother's milk developed changes in pancreatic
islets, resulting in overproduction of insulin and obesity in
The progeny of these high-carbohydrate (HC) mothers raised
naturally also develop the same maladjustments, they found.
The researchers now have shown that this metabolic
"malprogramming" is permanent and occurs in utero, resulting in the
next generation born to HC mothers carrying the HC phenotype. Rat
fetuses had increased plasma insulin levels, increased mRNA levels
of preproinsulin, a precursor of insulin, and increased insulin in
the pancreas, without an increase in body weight, plasma glucose
level or a change in islet structure.
They also found changes in the hypothalamus, the brain's center
of appetite regulation, that result in appetite stimulation.
While these studies were done with rats, Mulchand Patel, Ph.D,
UB distinguished professor of biochemistry and first author on the
study, speculated that there is good reason to think the mechanism
could be similar in humans.
"Obesity can be perpetuated via the maternal intrauterine
environment," said Patel, who reported the findings at the 2005
Experimental Biology meeting held in San Diego in early April.
"Our earlier studies looked at progeny in the post-weaning
period, so we didn't know how early this malprogramming occurred.
Now we know it occurs in utero. We predicted that this could be the
case, and our present findings support this prediction."
Plasma levels of rat pups (2-HC) born to HC mothers returned to
normal during the suckling period, results showed, but islets from
12-day-old suckling 2-HC rats showed a capacity for insulin
oversecretion when maintained in culture medium containing high
glucose levels. By the 28th day, approximately 4 days after weaning
to rat chow, 2-HC rats once again had high insulin levels and
showed a higher capacity for insulin secretion to a glucose
stimulus. Even on rat chow, body weight began to increase around
day 55, and 2-HC rats were obese by post-natal day 100.
Patel speculated that in humans, it's possible such
malprogramming could be interrupted if an obese/insulin resistant
mother brought body weight and plasma insulin levels back to normal
before becoming pregnant.
Malathi Srinivasan. Ph.D, Suhad Shbeir-ElDika, Ravikumar
Aalinkeel, Ph.D., Fei Song, Ph.D., Lioudmila Pliss, Ph.D., and Paul
Mitrani from Patel's lab, along with Roberta Pentney, Ph.D., from
the UB Department of Pathology and Anatomical Sciences, also
contributed to the study, as well as Shanthie Damodaran, Ph.D., and
Sherin Devaskar M.D., from the Department of Pediatrics at UCLA,
and Brenda Strutt and David Hill Ph.D., from the Lawson Research
Institute in London, Ontario.
The research was supported by grants from the National
Institutes of Health.