Fat Tissues In Sheep Affected By Prenatal Exposure To BPA

New research suggests that fetal exposure to the common environmental chemical bisphenol A, or BPA, causes increased inflammation in fat tissues after birth, which can lead to obesity and metabolic syndrome. Results of the animal study were presented at The Endocrine Society's 95th Annual Meeting in San Francisco.

Found in plastic water bottles, older baby bottles and many other consumer products, BPA is a known hormone disrupter with estrogen-like properties. Prior research has linked BPA in both animals and humans to obesity and the metabolic syndrome, which is a cluster of metabolic risk factors that increase the chance of later developing diabetes, heart disease and stroke.

"This research is the first study to show that prenatal exposure to BPA increases postnatal fat tissue inflammation, a condition that underlies the onset of metabolic diseases such as obesity, diabetes and cardiovascular disease," said the study's lead author, Almudena Veiga-Lopez, DVM, PhD, a research investigator at the University of Michigan, Ann Arbor.

She said the study, which examines the effects of BPA on sheep, improves the understanding of how prenatal BPA exposure regulates the inflammatory response in offspring in the tissues that are relevant to development of metabolic disease. The study was conducted in the laboratory of Vasantha Padmanabhan, MS, PhD, Professor at the University of Michigan, Ann Arbor, with funding from the National Institutes of Health's National Institutes of Environmental Health Sciences. Veiga-Lopez said sheep have similar body fat to that in humans, including visceral (deep belly) fat and subcutaneous fat, which is directly below the skin.

The researchers fed two groups of pregnant sheep corn oil, either with nothing added to it or with added BPA at a dose needed to achieve BPA levels similar to those seen in human cord blood in the umbilical cord blood of the sheep offspring. Of the female offspring from the sheep, half from each group were overfed at approximately 6 weeks of age. All female offspring then were divided into four groups of nine to 12 animals each: (1) non-BPA-exposed controls that received a normal diet, (2) BPA-exposed offspring that received a normal diet, (3) overfed, obese controls and (4) overfed, obese BPA-exposed offspring.

At 15 months of age, sheep underwent a glucose tolerance test, to measure their insulin and blood sugar levels. Seven months later, the researchers collected samples of the animals' visceral and subcutaneous fat tissues to evaluate levels of two biological markers of inflammation. These biomarkers were CD68, a marker for inflammatory cells, and adiponectin, a molecule with a known role in the development of metabolic syndrome. When the adiponectin level decreases or CD68 expression increases, inflammation is worse, according to Veiga-Lopez.

Adiponectin was decreased and CD68 expression was raised in the visceral fat of both obese groups, and CD68 expression also was raised in the subcutaneous fat in normal weight, BPA-exposed female offspring, Veiga-Lopez reported. She said these results suggest that "prenatal BPA exposure and postnatal diet may interact to modulate inflammatory mechanisms in fat deposits."

Both obese groups had hyperinsulinemia, or high insulin levels, a precursor to insulin resistance, which is a prediabetic state, Veiga-Lopez reported. However, she said prenatal exposure to BPA did not lead to insulin resistance in sheep, as was true in a previous mouse study. She speculated that the hyperinsulinemia in obese offspring stems from changes that occurred in the two inflammatory markers in the visceral fat deposit.

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New Tool To Measure Sugar Consumption

Scientists at the University of Alaska Fairbanks identified a new tool that can dramatically improve the notoriously inaccurate surveys of what and how much an individual eats and drinks. Their research is published in the June 2013 issue of the Journal of Nutrition.

Conventional wisdom says that consumption of sugar-sweetened beverages such as soda and fruit juice is a significant contributor to obesity and chronic disease risk, but the science surrounding this issue is inconclusive. Part of the problem is that in a typical diet survey few people accurately and consistently recall what they consumed. The problem becomes exaggerated when people underreport foods they know are less healthy for them, like sugars.

"We were looking for an objective biomarker that could accurately measure long-term sugar intake from a single blood or hair sample" said Diane O'Brien, project leader and biologist with the UAF Center for Alaska Native Health Research at the Institute of Arctic Biology.

The biomarker O'Brien and her CANHR research group pilot-tested was the ratio of two different carbon atoms (heavy carbon 13 and light carbon 12) which are incorporated into plants during photosynthesis. The ratio, called an isotopic signature, is distinct in corn and sugar cane, which are the sources of nearly all of the sugars found in sugar-sweetened beverages.

"We used the isotopic signature of alanine an amino acid and building block of protein that essentially traps the carbon from dietary sugar so that it can be measured in the protein component of hair or blood," O'Brien said.

Even after foods and beverages are consumed, metabolized, transported in blood and stored in body tissues, these isotopic signatures remain largely intact. The more sugar-sweetened beverages an individual consumes, the greater alanine's carbon isotope ratio will be. Importantly, O'Brien's group found that alanine was uncorrelated with other foods that can contribute to elevated carbon ratios.

Although the use of isotope signatures to study food webs and diet is not new, previous efforts to accurately measure sweetener intake have not been particularly successful. The use of alanine and the technique employed by O'Brien's group makes their findings particularly exciting.

"Even for validated and well-accepted biomarkers of diet, associations with self-reported intake are generally very weak. Our biomarker was able to explain almost half of the variation in self-reported sugar-sweetened beverage intake, which in this field is a very high level of explanatory power," said O'Brien.

The scientists' findings are also being used in other health and diet-related research.

"Diane's research program has provided CANHR with incredibly valuable objectively measured biomarkers of food intake," said CANHR Director Bert Boyer. "These biomarkers are currently being used to help us understand the role polyunsaturated fatty acids play in disease prevention, including the modification of genetic risk."

The tool is not without its drawbacks, caution the authors.

"The gas chromatography-combustion-isotope ratio mass spectrometry process we used isn't inexpensive and or widely available," O'Brien said. "We expect that our findings will be most useful as a calibration tool, either for self-reported dietary data or more high-throughput biomarkers of sweetener intake."

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