Infant nutrition found to programme metabolism, possibly leading to obesity

Consuming a milk formula high in carbohydrates during the critical early weeks of postnatal life causes permanent changes in metabolism making the infants more likely to develop obesity in later years, finds a study by University at Buffalo biochemists.

The study, presented at the Experimental Biology 2002 meeting in New Orleans, showed that changes to pancreatic islets, caused by the high carbohydrate diet leads to overproduction of insulin and then obesity in adulthood.

Furthermore, this "metabolic programming" carries through to the next generation. The study carried out on rats found that offspring of first-generation high-carbohydrate-fed (HC) female rats developed hyperinsulinemia (high insulin levels) and obesity without any dietary modification.

Dr Mulchand Patel, UB professor of biochemistry and senior author of the study, said that the study provides a new perspective on obesity.

"We are always looking at what happens later in life. Maybe we should be looking at the role of early metabolic programming,"​ he said.

"The results from this study involving the high-carbohydrate-fed rat model suggest that the foods human babies are fed as newborns may contribute to metabolic programming, leading to adult-onset diseases such as obesity and diabetes,"​ Patel added.

He claimed that overfeeding of formula and early introduction of supplemental weaning foods such as cereals, fruits and juices that are high in carbohydrates could be the culprits.

Metabolic programming has been studied before. Epidemiologic studies of malnourished mothers, which showed that their babies were often underweight and at increased risk for several chronic diseases as adults, led to the public health emphasis on adequate nutrition during pregnancy. Several animal studies on maternal protein malnourishment or caloric restriction have shown that pre- and immediate postnatal nutritional modifications have long-term consequences on adult-onset diseases.

"Metabolic signals are reset in response to a high carbohydrate diet, which induces permanent changes at the molecular level in our rat model,"​ Patel said, adding : "The HC phenotype is transferred from cell to cell, is expressed for life and is transmitted to succeeding generations."​

The University of Buffalo claims that Patel and colleagues were the first to manipulate the composition of the diet - the percentages of carbohydrates and fat while keeping calories constant - in order to study the metabolic programming effect. Milk produced by the rat mother is composed of 8 per cent carbohydrate, 68 per cent fat and 24 per cent protein; the modified milk formula fed to the rat babies in the UB study was composed of 56 per cent carbohydrate, 20 per cent fat and 24 per cent protein.

The animals were raised for the first 24 days, the natural suckling period, using a technique dubbed "pup in a cup," which involved placing 4-day-old rat pups in Styrofoam cups floating in a temperature-controlled water bath and delivering the modified formula directly into the stomach. Rat pups reared in this manner received a formula comparable in calories to mother's milk, and rat pups nursed by their mothers served as controls.

The high-carbohydrate pups developed high insulin levels within 24 hours and these levels persisted throughout adulthood, even after the rats were weaned onto rat chow, Patel said. The researchers found alterations in the insulin secretory pathway of pancreatic islet cells and molecular changes that induced increased expression of preproinsulin, a precursor of insulin. At two months, the HC rats started gaining weight and eventually became obese.

What happened with the offspring of HC rats was not expected, however, Patel said. The second generation HC rats developed hyperinsulinemia without receiving the high carbohydrate diet and became obese in adult life. Only the HC females transmit these traits to their progeny, he said, suggesting that the intrauterine experience may be essential for transmission of the metabolic programming.

The scientist noted that a parallel situation may exist with the overfeeding of human babies.

"Babies who were formula-fed when it was popular in the 1950s and '60s may have developed obesity as adults and may have passed on this trait to their children. With breast feeding, the mother produces an adequate amount of milk naturally. With formula feeding, the tendency is to finish the bottle, and this may result in overfeeding,"​ Patel said.

"It's evident from our studies with rats that the composition and the timing of the dietary treatment programs the onset of pathological conditions in the adults that mimic major metabolic diseases noted in humans, such as obesity and type 2 diabetes,"​ he added.

The newly emerging field of metabolic programming offers an additional route to examine the development of chronic diseases of adulthood, according to Patel.

The researchers aim eventually to determine the mechanisms causing the hyperinsulinemic phenotype to be expressed for life in the first generation, and what factors in the mother are responsible for spontaneous transmission of this trait to the offspring.