Details of the work, which appear in Nature Communications, centre on how two food preservatives along with a polymer found in cookware, disrupt a trio of hormones that play a role in appetite control.
The innovative stem-cell testing system used also demonstrates how a defective hormone system could affect a pregnant mother and her foetus – a process only observed in animal studies.
“This is a landmark study that substantially improves our understanding of how endocrine disruptors may damage human hormonal systems and contribute to the obesity epidemic," said Dr Clive Svendsen, director of Regenerative Medicine Institute at Cedars-Sinai Medical Center.
Endocrine disrupting chemicals (EDCs) like organotins, perfluorochemicals, and food additives are thought to be contributors towards the obesity epidemic.
Tributyltin (TBT) is known to bioaccumulate in seafood and has posed the most exposure risk to humans.
Butylhydroxytoluene (BHT), a common food additive and an ingredient in personal care cosmetics, pesticides, plastic, and rubber is also used as an antioxidant in commonly consumed breakfast cereal brands.
The European Food Safety Authority (EFSA) ruled in 2012 that BHT or E321, was safe at an Acceptable daily intake (ADI) level of 0.25 milligrams/kilogram/bodyweight per day (mg/kg bw/day). This was revised from an ADI value of 0.05 mg/kg bw/day.
Led by Dr Dhruv Sareen, assistant professor of Biomedical Sciences at the Cedars-Sinai Medical Center, the team used hormone-producing tissues grown from human pluripotent stem cells in their experiments.
This was achieved by first obtaining blood samples from adults and then inserting reprogramming genes. These genes converted the cells into induced pluripotent stem cells.
The team were then able to grow human epithelium tissue, which lines the gut, along with neuronal tissues of the brain's hypothalamus region, which regulates appetite and metabolism.
This tissue type was then exposed to BHT, TBT, and perfluorooctanoic acid (PFOA), a polymer found in cookware, carpeting and other products.
Findings pointed towards a disruptive nature to the hormones Peptide YY (PYY), α-Melanocyte-stimulating hormone (α-MSH), and cocaine and amphetamine-regulated transcript (CART).
The chemicals specifically interfered with these signalling hormones by distorting their chemical structure, which disabled the process by which they were transported out of cells.
The chemicals also damaged the mitochondria that convert food and oxygen into energy and drive the body's metabolism.
“We discovered that each of these chemicals damaged hormones that communicate between the gut and the brain," said Dr Sareen,
"When we tested the three together, the combined stress was more robust."
Dr Sareen explained that because the chemical damage occurred in early-stage "young" cells, the developmental programming of the human foetus may be more susceptible to alterations in endocrine system and metabolic development, and predisposing offspring to metabolic disorders.
“Intricate crosstalk between unhealthy mitochondria and a stressed unfolded protein response (UPR) may negatively impacting production and secretion of gut–brain hormonal peptides during critical periods of early human development,” the study commented.
According to the World Health Organisation (WHO), estimates of the number of overweight infants and children in the European Region rose steadily from 1990 to 2008.
Over 60% of children who are overweight before puberty will be overweight in early adulthood.
Source: Nature Communications
Published online ahead of print: doi:10.1038/s41467-017-00254-8
“Endocrine disruptors induce perturbations in endoplasmic reticulum and mitochondria of human pluripotent stem cell derivatives.”
Authors: Uthra Rajamani, Andrew Gross, Camille Ocampo, Allen Andres, Roberta Gottlieb & Dhruv Sareen