The role of the adipocyte glucocorticoid receptor in energy metabolism and HPA axis regulation

Appetite ◽  
2011 ◽  
Vol 57 ◽  
pp. S12
Author(s):  
A.D. De Kloet ◽  
E.G. Krause ◽  
M.B. Solomon ◽  
J.N. Flak ◽  
K.A. Scott ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Glucocorticoid Receptor ◽  
Hpa Axis

scholarly journals Mechanistic insights on metabolic dysfunction in PTSD: Role of glucocorticoid receptor sensitivity and energy deficit

2018 ◽  
Author(s):  
Pramod R. Somvanshi ◽  
Synthia H. Mellon ◽  
Janine D. Flory ◽  
Duna Abu-Amara ◽  
Owen M. Wolkowitz ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Metabolic Control Analysis ◽  
Energy Deficit ◽  
Control Analysis ◽  
Metabolic Dysfunction ◽  
Receptor Sensitivity ◽  
Regulatory Effects ◽  
Metabolic Comorbidities

AbstractPTSD is associated with metabolic comorbidities; however it is not clear how the neuroendocrine disturbances affect metabolism. To analyze this we employed a systems biological approach using an integrated mathematical model of metabolism, HPA axis and inflammation. 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. We used the pattern of fold change in metabolites representing pathway level differences as reference for metabolic control analysis (MCA) using the model. MCA revealed parameters constituting the HPA axis, inflammation and GPCR pathway that yielded metabolic dysfunction consistent with PTSD. To support this, we performed causal analysis between regulatory components and the significantly different metabolites in our sample. Causal inference revealed that the changes in glucocorticoid receptor sensitivity were mechanistically associated with metabolic dysfunction and the effects were jointly mediated by insulin resistance, inflammation, oxidative stress and energy deficit.

scholarly journals Role of the Glucocorticoid Receptor in Systemic Energy Metabolism

2018 ◽  
Vol 107 (7) ◽  
pp. 1373-1384
Author(s):  
Hirotoshi Tanaka ◽  
Noritada Yoshikawa ◽  
Hiroki Yamazaki ◽  
Masaaki Uehara ◽  
Aya Oda
Keyword(s):  
Energy Metabolism ◽  
Glucocorticoid Receptor

Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis

2005 ◽  
Vol 289 (5) ◽  
pp. E857-E863 ◽  
Author(s):  
Anastasia Kariagina ◽  
Svetlana Zonis ◽  
Mahta Afkhami ◽  
Dmitry Romanenko ◽  
Vera Chesnokova
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Leukemia Inhibitory Factor ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Inhibitory Factor ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Protein Levels

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 μg/mouse, ip) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation.

The Hypothalamic-Pituitary-Adrenal Axis: A Brief History

2018 ◽  
Vol 89 (4) ◽  
pp. 212-223 ◽  
Author(s):  
Walter L. Miller
Keyword(s):  
Complex System ◽  
Energy Metabolism ◽  
Hpa Axis ◽  
Stress Responses ◽  
Clinical Investigation ◽  
Hypothalamic Pituitary Adrenal ◽  
History Of ◽  
Complex Chemistry ◽  
Pituitary Adrenal Axis

The hypothalamic-pituitary-adrenal (HPA) axis is central to homeostasis, stress responses, energy metabolism, and neuropsychiatric function. The history of this complex system involves discovery of the relevant glands (adrenal, pituitary, hypothalamus), hormones (cortisol, corticotropin, corticotropin-releasing hormone), and the receptors for these hormones. The adrenal and pituitary were identified by classical anatomists, but most of this history has taken place rather recently, and has involved complex chemistry, biochemistry, genetics, and clinical investigation. The integration of the HPA axis with modern neurology and psychiatry has cemented the role of endocrinology in contemporary studies of behavior.

scholarly journals The Role of the Forebrain Glucocorticoid Receptor in Acute and Chronic Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5482-5490 ◽  
Author(s):  
Amy R. Furay ◽  
Amy E. Bruestle ◽  
James P. Herman
Keyword(s):  
Glucocorticoid Receptor ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Basolateral Amygdala ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Acute And Chronic Stress ◽  
Corticosterone Secretion

Previous work has implicated the forebrain glucocorticoid receptor (GR) in feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present series of experiments used male mice with a targeted forebrain-specific GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and basolateral amygdala) to determine the role of forebrain GR in HPA axis regulation after stress. The data indicate that the forebrain GR is necessary for maintaining basal regulation of corticosterone secretion in the morning, confirming its role in HPA axis regulation. Our data further indicate that the forebrain GR is necessary for negative feedback after both mild and robust acute psychogenic stressors but not hypoxia, a systemic stressor. In contrast, forebrain-specific GR knockout and control mice exhibit equivalent HPA axis hyperactivity and facilitation after chronic variable stress, suggesting that changes in forebrain GR are not essential for chronic stress-induced pathology. These studies provide novel and definitive evidence that the forebrain GR selectively contributes negative feedback regulation of HPA axis responses to psychogenic stressors. Moreover, the data indicate that chronic stress-induced alterations in HPA axis function are mediated by mechanisms independent of the forebrain GR. Overall, the data are consistent with an essential role of the forebrain GR in coordinating endocrine responses to stimuli of a psychological origin.

Mitochondrial matrix calcium ions regulate energy production in myocardium: A cytochemical study

1990 ◽  
Vol 48 (2) ◽  
pp. 166-167
Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet
Keyword(s):  
Energy Metabolism ◽  
Calcium Ions ◽  
Energy Production ◽  
Regulation Of Respiration ◽  
Free Calcium ◽  
Mitochondrial Matrix ◽  
Cytochemical Study ◽  
Nmr Techniques

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.

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