Obesity is a worldwide epidemic that is influenced by a combination of factors, such as lifestyle choices, stress levels and genetics. Each of these individual aspects, or a combination, can significantly alter a person's development, starting early in the womb and continuing into adulthood. But which of these components, or their interactions, are key to understanding the obesity epidemic and its detrimental effects on longevity and quality of life?

Erin Faught and Matt Vijayan, two researchers at the University of Calgary, Canada decided to tackle this monumental question by examining how the interaction between stress and genes during early development impacts fat accumulation and breakdown in the body. For their work, the team turned to zebrafish, small unassuming tropical fish that are quickly becoming a superhero of medical research because their genes can be mutated easily, allowing researchers to learn more about the roles of these genetic elements during growth and development. Faught created two groups of zebrafish, each with a mutation in the genes encoding one of two receptors – the glucocorticoid receptor and the mineralocorticoid receptor – for the stress hormone cortisol. The researchers made these mutations so that they could compare the mutated fish with normal fish to figure out which of these receptors is activated during stress and how that activation affects fat accumulation and breakdown in the body.

Working with zebrafish embryos, the duo exposed both mutated and normal youngsters to either cortisol (i.e. stressed fish) or no cortisol (i.e. non-stressed fish) conditions from 3 days post-fertilization (dpf) up to 15 dpf. The researchers did this to simulate a stressful environment during development and compare the response with that of the non-stressed animals. By the end of the 15 days, the non-stressed fish with an intact mineralocorticoid receptor gene accumulated more fat than those with this gene mutated. The authors also found that mineralocorticoid and glucocorticoid receptors work together: the mineralocorticoid receptor allows the embryos to accumulate fat when there is no stress during development, while the glucocorticoid receptor is activated during stress, to mobilize energy and allow the organism to overcome the challenge. In addition, the receptors work together to increase lipid breakdown, allowing the fish to use the fat they accumulated from food as an energy source and cope with the stress. Faught and Vijayan concluded that the mineralocorticoid receptor is essential during development to allow lipid accumulation. They also suggest that exposure to stress during development, particularly in children, may lead to deficiencies in how the organism is using those lipids and how efficient it is at breaking them down. The authors conclude that these findings may help us to understand the influence of stress on gene expression and how exposure to a stressful environment early in development may lead to genetic disorders and obesity.

While this study has shown a clear interaction between genetics and stress during early development, and how one can influence the other, it raises more questions. Can we predict the effects of stress on adults based on their experiences during development and early life? What effects does early exposure to chronic stress have on the way adults cope with stress and fat storage/breakdown later in life? Could genetic manipulation of genes such as the mineralocorticoid receptor be the answer to human metabolic diseases and offer the hope of personalized medicine for all? Only more research and time will tell.

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Postnatal triglyceride accumulation is regulated by mineralocorticoid receptor activation under basal and stress conditions
J. Physiol.