Rodents studies have shown that the animals subjected to stress put on more weight when fed high fat diets than they do eating the same diet without the added stress. Findings suggest additional weight gain is triggered by activation of brain molecular pathways controlled by insulin, which results in reduced energy expenditure so the body doesn’t use as many calories when stressed.
When stressed humans tend to adopt one of two eating patterns preferring to select food options with higher sugar and fat content by either eating less and losing weight; or increasing food intake. The researchers note, “… during times of stress, most people report an increase in the intake of highly palatable foods, independent of overall hyperphagia or hypophagia.”
Under stressed conditions the hypothalamus, pituitary, and adrenal gland signalling is implicated in feeding behaviors, and is intertwined with hormonal systems involved with appetite regulation; the energy balance is suggested to be in part regulated by HPY activated feedback loops involving the hormones insulin, leptin, glucocorticoids, and neuropeptide Y.
Neuropeptide Y is an anxiolytic peptide expressed in the amygdala and has been implicated in regulation of emotional eating due to its role in responses to stress in psychiatric disorders. “Therefore, dynamic changes in Npy expression levels in the amygdala in response to stress may be an important biochemical signal underlying stress-dependent eating. While the role of amygdala-derived NPY in regulating fear and anxiety has been well studied, the part it plays in regard to the regulation of feeding and energy homeostasis is largely unknown.”
A previously unknown feeding stimulatory pathway activated during times of stress when combined with availability of high calorie foods was identified through a series of mice either fed normal, or high fat diets while being either under stress or non-stressed conditions. NPY neurons in the central amygdala region of the brain play critical roles in increasing food intake and decreasing energy expenditure under these conditions, thus the mice under stress with access to high fat foods put on more weight than those given the same diet without stress. “Chronic stress was shown to effectively activate the NPY system, reinforcing food consummatory behavior and also inducing a stress-dependent energy conservation state leading to an exacerbated development of obesity.”
“Our study showed that when stressed over an extended period and high-calorie food was available, mice became obese more quickly than those that consumed the same high-fat food in a stress-free environment,” commented Kenny Chi Kin Ip, PhD.
Neuropeptide Y is produced by the brain naturally in response to stress to stimulate eating in humans and in mice; chemogenetically activating NPY neurons in the amygdala triggered increased feeding dependent on presence of NPY. “… even when only a normal chow diet is provided, the acute specific activation of CeA NPY neurons by chemogenetic tools is sufficient to increase food intake and lower EE. Conversely, blocking NPY production had the opposite effect. We discovered that when we switched off the production of NPY in the amygdala weight gain was reduced. Without NPY, the weight gain on a high-fat diet with stress was the same as weight gain in the stress-free environment. This shows a clear link between stress, obesity, and NPY.”
Additional studies showed NYP neurons to harbor insulin receptors, and the combination of stress and high calorie diets boosted insulin levels 10 fold compared to blood levels of insulin in stress free animals with normal diets. Prolonged high levels of insulin in the amygdala of the high fat diet stressed animals effectively caused the NPY neurons to become desensitized to the hormone, which in turn increased NPY levels that triggered the mice to eat more while having the effect of reducing body energy expenditure. Overeating hat fat diet animals under non-stressed conditions led to an increase in energy expenditure in response to increase food intake, “in an attempt to maintain the original homeostatic set point.”
Knocking out insulin receptors specifically in the amygdala NPY neurons had the same effect as the combination of stress and high fat diets leading to increased body weight. “… our data suggest that loss of regulatory function of insulin signaling specifically on CeA Npy expression is a key contributor to the accelerated obese phenotype seen under chronic stress.”
“This really reinforced the idea that while it’s bad to eat junk food, eating high-calorie foods under stress is a double whammy that drives obesity. We were surprised that insulin had such a significant impact on the amygdala. It’s becoming more and more clear that insulin doesn’t only impact peripheral regions of the body, but that it regulates functions in the brain. We’re hoping to explore these effects further in the future.”
