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The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances

1
Immune Endocrine and Epigenetics Research Group, Department of Infection and Immunity, Luxembourg Institute of Health (LIH), L-4354 Esch-sur-Alzette, Luxembourg
2
Faculty of Science, Technology and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg
*
Author to whom correspondence should be addressed.
Academic Editor: Gil Atzmon
Int. J. Mol. Sci. 2021, 22(7), 3344; https://doi.org/10.3390/ijms22073344
Received: 28 February 2021 / Revised: 18 March 2021 / Accepted: 23 March 2021 / Published: 25 March 2021
(This article belongs to the Special Issue Epigenetic and Molecular Consequences of Early-Life Trauma)
The physiological response to a psychological stressor broadly impacts energy metabolism. Inversely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA), and sympathetic nervous system activation. Glucocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of energy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance, and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, and the most prominent are early life adversity, or exposure to traumatic stress. We hypothesise that when the HPA axis is so disturbed after early life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered. View Full-Text
Keywords: glucose; glycogen; gluconeogenesis; early life adversity; acute stress; chronic stress; psychosocial stress; hypothalamus-pituitary-adrenal axis; ageing; immuno-senescence; inflamm-ageing; developmental origins of health and disease glucose; glycogen; gluconeogenesis; early life adversity; acute stress; chronic stress; psychosocial stress; hypothalamus-pituitary-adrenal axis; ageing; immuno-senescence; inflamm-ageing; developmental origins of health and disease
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MDPI and ACS Style

Seal, S.V.; Turner, J.D. The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances. Int. J. Mol. Sci. 2021, 22, 3344. https://doi.org/10.3390/ijms22073344

AMA Style

Seal SV, Turner JD. The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances. International Journal of Molecular Sciences. 2021; 22(7):3344. https://doi.org/10.3390/ijms22073344

Chicago/Turabian Style

Seal, Snehaa V.; Turner, Jonathan D. 2021. "The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances" Int. J. Mol. Sci. 22, no. 7: 3344. https://doi.org/10.3390/ijms22073344

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