Between the end of childhood and the beginning of adolescence, there is a critical window of time referred to as “peripuberty”. This transitional period involves developmental changes in both fat tissue and in the brain in which both can be re-programmed by exposure to stress which can cause long-lasting changes in the size of fat cells (adipocytes) size and composition, as well as social behavior.
In a new study, scientists led by Professor Carmen Sandi at EPFL, have found that stress during the peripubertal period leads to increases in adipose tissue in the individual’s body. Although previous studies have shown this connection, there has been little in the way of identifying a biological link between the increase of adipose tissue seen in peripuberty and social impairment.
The study is published in Science Advances.
“We know that stress can induce psychopathologies, including depression,” says Sandi. “Some of the characteristic behavioral changes that you see in depression are alterations in the individual’s sociability, meaning that some depressed people tend to be more retracted, a bit social-avoidant; some can even develop social anxiety.”
Stress, sociability, and mice
In the study, Sandi’s group uncover two insights in the field: first, that peripubertal stress leads to an increase in adipose tissue and reduces sociability at the same time. Second, how the two changes phenomena are biologically related.
“We explored whether alterations in fat composition -induced by stress in early life- could be responsible of inducing changes in the brain that, ultimately, would cause alterations in social behavior in a protracted manner,” says Sandi.
To study peripubertal stress, the researchers needed a model. They turned to mice, within the peripubertal window of age, and exposed them to chronic, unpredictable stress. A study of their body composition revealed an overall increase of fat mass and larger adipocytes.
Upon reaching adulthood, the mice were tested on social tasks. Male mice showed a life-long decrease in sociability as their adipose tissue increased but, interestingly, female mice showed no such effect. But whether or not there is a sex-dependent difference in other psychobiological adaptations is something that Sandi’s group will study in the future.
“What we focused here was in the reduction in sociability that you see in depression,” says Sandi. “We know also from epidemiological studies in humans, that it can be linked with early life stress – peripubertal stress, which can program people to be less sociable.”
The NAD+ connection
The researchers then set off to identify the underlying biology. A series of tests pointed to a specific enzyme called adipokine nicotinamide phosphoribosyltransferase, (NAMPT), which is known to be involved in some of the pathological metabolic problems caused by obesity.
In the body, NAMPT exists in two forms: an intracellular form, which regulates the production of nicotinamide adenine dinucleotide (NAD+), an important molecule for the generation …….