Mechanistic inferences on metabolic dysfunction in PTSD from an integrated model and multi-omic analysis: Role of glucocorticoid receptor sensitivity.

Mechanistic inferences on metabolic dysfunction in PTSD from an integrated model and multi-omic analysis: Role of glucocorticoid receptor sensitivity. Am J Physiol Endocrinol Metab. 2019 Jul 19;: Authors: Somvanshi PR, Mellon SH, Flory JD, Abu-Amara D, Consortium PSB, Wolkowitz OM, Yehuda R, Jett M, Hood L, Marmar C, Doyle FJ Abstract Post-traumatic stress disorder is associated with neuroendocrine alterations and metabolic abnormalities; however, how metabolism is affected by neuroendocrine disturbances is unclear. The data from combat exposed veterans with PTSD shows increased glycolysis to lactate flux, reduced TCA cycle flux, impaired amino acid and lipid metabolism, insulin resistance, inflammation and hypersensitive HPA-axis. To analyze whether the co-occurrence of multiple metabolic abnormalities are independent, or arises from an underlying regulatory defect, we employed a systems biological approach using an integrated mathematical model and multi-omic analysis. The models for hepatic metabolism, HPA axis, inflammation and regulatory signaling were integrated to perform metabolic control analysis (MCA) with respect to the observations from our data. We combined the metabolomics, neuroendocrine, clinical lab and cytokine data from combat-exposed veterans with and without PTSD to characterize the differences in regulatory effects. MCA revealed mechanistic association of the HPA-axis and inflammation with metabolic dysfunction ...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research