Print Email Facebook Twitter The hypothalamic- pituitary -adrenal -leptin axis and metabolic health: A systems approach to resilience, robustness and control Title The hypothalamic- pituitary -adrenal -leptin axis and metabolic health: A systems approach to resilience, robustness and control Author Aschbacher, K. Rodriguez-Fernandez, M. van Wietmarschen, H. Tomiyama, A. Jain, S. Epel, E. Doyle III, F.J. van der Greef, J. Publication year 2014 Abstract Glucocorticoids contribute to obesity and metabolic syndrome; however, the mechanisms are unclear, and prognostic measures are unavailable. A systems level understanding of the hypothalamic-pituitary-adrenal (HPA) -leptin axis may reveal novel insights. Eighteen obese premenopausal women provided blood samples every 10 min over 24 h, which were assayed for cortisol, adrenocorticotropin releasing hormone (ACTH) and leptin. A published personalized HPA systems model was extended to incorporate leptin, yielding three parameters: (i) cortisol inhibitory feedback signalling, (ii) ACTH- adrenal signalling, and (iii) leptin-cortisol antagonism. We investigated associations between these parameters and metabolic risk profiles: fat and lean body mass (LBM; using dual-energy X-ray absorptiometry), and insulin resistance. Decreased cortisol inhibitory feedback signalling was significantly associated with greater fat (kg; p=0.01) and insulin resistance (p=0.03) but not LBM. Leptin significantly antagonized cortisol dynamics in eight women, who exhibited significantly lower 24 h mean leptin levels, LBM and higher ACTH-adrenal signalling nocturnally (all p<0.05), compared with women without antagonism. Traditional neuroendocrine measures did not predict metabolic health, whereas a dynamic systems approach revealed that lower central inhibitory cortisol feedback signalling was significantly associated with greater metabolic risk. While exploratory, leptin-cortisol antagonism may reflect a 'neuroendocrine starvation' response. © 2014 The Authors. Subject LifeMSB - Microbiology and Systems BiologyELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingDynamic systemsMetabolic syndromeObesityPsychological stressRobustnessStress-eating To reference this document use: http://resolver.tudelft.nl/uuid:d5019007-b24c-4bf7-a086-41af240cfe15 DOI https://doi.org/10.1098/rsfs.2014.0020 TNO identifier 516518 ISSN 2042-8898 Source Interface Focus, 4 (5) Article number 20140020 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.