Chronic Stress Impacts on Metabolism and Behavioral Physiology

Chronic stress induces a cascade of neuroendocrine and metabolic adaptations that, over time, undermine physiological balance and alter behaviour. Sustained activation of the hypothalamic–pituitary–adrenal (HPA) axis elevates circulating glucocorticoids, shifting energy allocation towards immediate survival needs and away from long-term homeostatic processes. As a result, individuals may exhibit hyperphagia or hypophagia, impaired glucose tolerance, insulin resistance and aberrant lipid metabolism. In parallel, prolonged stress remodels brain circuits governing mood, motivation and reward, manifesting as anxiety-like or depressive-like behaviours, social withdrawal and cognitive inflexibility. Peripheral tissues such as liver, adipose and muscle respond to stress hormones by modulating gene networks involved in inflammation, mitochondrial function and oxidative balance, further compounding metabolic dysregulation. Animal models of chronic unpredictable stress reveal that disturbances in energy expenditure, adipokine secretion and insulin signalling co-occur with altered locomotor activity, social hierarchies and coping strategies. Together, these findings underscore the bidirectional interplay between metabolic state and behavioural physiology under chronic stress, with implications for the development of metabolic syndrome, mood disorders and resilience-enhancing interventions.

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Chronic Stress Impacts on Metabolism and Behavioral Physiology publication trend

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Technical terms

Hypothalamic–pituitary–adrenal (HPA) axis: The neuroendocrine system coordinating the stress response through secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and glucocorticoids. Allostasis: The process by which the body achieves stability through physiological or behavioural change in response to stress. Energy homeostasis: The balance of energy intake, expenditure and storage that maintains body weight and metabolic function. Insulin resistance: A state in which cells in peripheral tissues respond inadequately to insulin, leading to impaired glucose uptake. Chronic unpredictable stress (CUMS): An animal paradigm involving varied mild stressors applied over weeks to model prolonged psychological stress. Transcriptome: The complete set of RNA transcripts produced by the genome under specific conditions, reflecting gene expression patterns. Adipokine: A bioactive peptide secreted by adipose tissue that modulates metabolism, inflammation and insulin sensitivity.

References

1. Effect of Short-Term Restraint Stress on the Hypothalamic Transcriptome Profiles of Rats with Inherited Stress-Induced Arterial Hypertension (ISIAH) and Normotensive Wistar Albino Glaxo (WAG) Rats. International Journal of Molecular Sciences (2024).
2. Energy Homeostasis-Associated (Enho) mRNA Expression and Energy Homeostasis in the Acute Stress Versus Chronic Unpredictable Mild Stress Rat Models. Biomedicines (2023).
3. Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats. Physiological Reports (2014).