Stress during peripuberty leads to increase in adipose tissue: Study
Peripuberty is a natural change that every person’s body undergoes when childhood ends and adolescence begins. A new study found that stress during the peripubertal period leads to an increase 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 transitional period of peripuberty involves developmental changes in both fat tissues 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.
We know that stress can induce psychopathologies, including depression, said the author. Some of the characteristic behavioural changes that you see in depression are alterations in the individuals’ sociability, meaning that some depressed people tend to be more retracted, a bit social-avoidant; some can even develop social anxiety, she added.
In the study, researchers uncovered 2 insights in the field: 1st, that peripubertal stress leads to an increase in adipose tissue and reduces sociability at the same time. 2nd, how the 2 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 behaviour in a protracted manner, she said.
To study, peripubertal stress, the researchers needed a model. They turned to mice, within the peripubertal window 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, a female mice showed no such effect. But whether or not there is a sex-dependent difference in other psychological adaptations is something that the researchers will study in the future.
What we focused here was in the reduction in sociability that you see in depression, she said. 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, she added.
The researchers then set off to identify the underlying biology. A series of tests pointed to a specific enzyme called adipokine nicotinamide phosphoribosyltransferease, (NAMPT), which is known to be involved in some of the pathological metabolic problems caused by obesity.
In the body, NAMPT exists in 2 forms: an intracellular form, which regulates the production of nicotinamide adenine dinocleotide (NAD+), an important molecule for the generation of energy in the cell. In its extracellular form, (eNAMPT), the enzyme is present in the blood.
The researchers found that the mice that had been stressed at peripuberty sowed a drop in the amount of NAMPT in fat cells and, consequently, of eNMPT in their blood at adulthood compared to non-stressed mice.
Looking at the nucleus accumbens- a brain region that regulates motivated behaviours of both the socially impaired and healthy, “ control”, mice, the researchers identified lower NAD+ levels and problems with the enzyme Sirtuin-1, an enzyme that depends on NAD+ to regulate the expression of genes involved in helping the cell regulate itself in response to stressors.
Since peripubertally stressed mice lad lower NAD+, we assessed, whether the effects we saw in sociability involved the actions of Sirtuin-1, said the author. Using multiple approaches, we demonstrated that this is indeed the case, meaning that peripubertal stress leads to protracted changes at multiple levels that link fat with brain function and behaviour, she added.
Peripubertal stress leads to reduced levels of NAMPT in adipose tissues and eNAMPT in blood, she said.
The latter was related to a reduction in NAD+ in the nucleus accumbens where we found a reduced NAD-dependent activity of Sirtuin-1, she added. The group found that this impairment affects the function of medium spiny neuron from the nucleus accumbens and ultimately, promotes a reduction in sociability.
Having implicated the NAD+ / Sirtuin-1 pathway in the nucleus accumbens, the team tried to see if they could help protect against the impact of peripubertal stress in the mice. They did this in 2 ways- either bringing blood levels of eNAMPT back to normal or feeding the mice with nicotinamide mononucleotide (NMN), an NAD+ booster. The 2 approaches worked, preventing both impairments in sociability and also alteration in nucleus accumbens neuronal excitability.
But are NAD+ boosters, which are popular in the US and the EU, but not in the Swiss market, a solution to treating the social impact of stress increasingly observed nowadays in the youth. Sandi is cautious: we have to be careful because we applied nutritional treatments in our study at adulthood, she said.
We are not saying that stressed kids or adolescents should take NMN, it will be important to analyze first of they have reduced plasma levels of NMN or eNAMPT, and to perform targeted studies to see the efficiency of this approach for younger populations. So, what makes sense is to restore low metabolic levels, not to treat everyone in the same way if there is no biological reason, she added.