Glucocorticoid hormones and energy homeostasis

Guia, Roldan M. de; Rose, Adam J.; Herzig, Stephan

doi:10.1515/hmbci-2014-0021

Cited by 52 publications

(61 citation statements)

References 143 publications

(164 reference statements)

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“…5A-C). Olanzapine deregulates hepatic cholesterol and triglyceride metabolism in apoE -/-mice Hepatic cholesterol and triglyceride metabolism are crucial factors for maintaining the homeostasis of the lipid pool [13,14]. Thus, the effects of olanzapine on hepatic de novo lipogenesis, lipoprotein metabolism, triglyceride synthesis, and secretion, as well as fatty acid oxidation were investigated.…”

Section: Olanzapine Deregulates Cholesterol Flux and Aggravates Inflamentioning

confidence: 99%

“…The liver is the major organ for both cholesterol production and cholesterol excretion from the human body [13,14]. The balance between the delivery of apoB-containing lipoproteins (chylomicron remnants, very low-density lipoprotein [VLDL], intermediatedensity lipoprotein and LDL) from the liver to peripheral tissues and high-density lipoprotein (HDL)-mediated reverse-cholesterol transport from tissues back to the liver is a crucial mechanism for maintaining the appropriate levels of circulating cholesterol [15].…”

Section: Introductionmentioning

confidence: 99%

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Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Chen

Shyue

Hsu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Olanzapine, an atypical antipsychotic drug, has therapeutic effects for schizophrenia. However, clinical reports indicate that patients taking atypical antipsychotic drugs are at high risk of metabolic syndrome with unclear mechanisms. We investigated the effect of olanzapine on atherosclerosis and the mechanisms in apolipoprotein E-null (apoE^-/-) mice. Methods: ApoE^-/- mice were used as in vivo models. Western blot analysis was used to evaluate protein expression. Conventional assay kits were applied to assess the levels of cholesterol, triglycerides, free cholesterol, cholesteryl ester, fatty acids, glycerol, and cytokines. Results: Daily treatment with olanzapine (3 mg/kg body weight) for four weeks increased mean arterial blood pressure and the whitening of brown adipose tissue in mice. In addition, olanzapine impaired aortic cholesterol homeostasis and exacerbated hyperlipidemia and aortic inflammation, which accelerated atherosclerosis in mice. Moreover, lipid accumulation in liver, particularly total cholesterol, free cholesterol, fatty acids, and glycerol, was increased with olanzapine treatment in apoE^-/- mice by upregulating the expression of de novo lipid synthesis-related proteins and downregulating that of cholesterol clearance- or very low-density lipoprotein secretion-related proteins. Conclusion: Olanzapine may exacerbate atherosclerosis by deregulating hepatic lipid metabolism and worsening hyperlipidemia and aortic inflammation.

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Section: Olanzapine Deregulates Cholesterol Flux and Aggravates Inflamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Chen

Shyue

Hsu

et al. 2018

Cell Physiol Biochem

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“…The involvement of GR in liver glucose metabolism has been established for a long time. In particular, hepatic gluconeogenesis is essential for maintenance of blood glucose levels in a normal range after prolonged fasting (31). We found that hGR␤ overexpression in the livers of WT mice significantly decreased hepatic gluconeogenesis, while hGR␤ did not have this effect in the livers of GRLKO mice.…”

Section: Discussionmentioning

confidence: 62%

Human Glucocorticoid Receptor β Regulates Gluconeogenesis and Inflammation in Mouse Liver

Cruz‐Topete

Oakley

et al. 2016

Molecular and Cellular Biology

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bWhile in vitro studies have demonstrated that a glucocorticoid receptor (GR) splice isoform, ␤-isoform of human GR (hGR␤), acts as a dominant-negative inhibitor of the classic hGR␣ and confers glucocorticoid resistance, the in vivo function of hGR␤ is poorly understood. To this end, we created an adeno-associated virus (AAV) to express hGR␤ in the mouse liver under the control of the hepatocyte-specific promoter. Genome-wide expression analysis of mouse livers showed that hGR␤ significantly increased the expression of numerous genes, many of which are involved in endocrine system disorders and the inflammatory response. Physiologically, hGR␤ antagonized GR␣'s function and attenuated hepatic gluconeogenesis through downregulation of phosphoenolpyruvate carboxykinase (PEPCK) in wild-type (WT) mouse liver. Interestingly, however, hGR␤ did not repress PEPCK in GR liver knockout (GRLKO) mice. In contrast, hGR␤ regulates the expression of STAT1 in the livers of both WT and GRLKO mice. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated that hGR␤ binds to the intergenic glucocorticoid response element (GRE) of the STAT1 gene. Furthermore, treatment with RU486 inhibited the upregulation of STAT1 mediated by hGR␤. Finally, our array data demonstrate that hGR␤ regulates unique components of liver gene expression in vivo by both GR␣-dependent and GR␣-independent mechanisms.

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“…As we failed to examine cellspecific fluctuations in PC1 and PC2 upon Sirt1 manipulation, and instead analyzed PVN micropunches for PC content, it is possible that a down-regulation in PC1 (presumably in CRH neurons) due to central Sirt1 inhibition may be offset by ␣-MSH's induction of PVN PC1 (presumably in TRH neurons). Alternatively, glucocorticoid receptor resistance has also been reported in obese individuals (60,61), and a study revealed that adrenalectomy increased the expression of PC1 in hypophysiotropic CRH neurons, an effect that was blunted via administration of exogenous GCs (59). We have shown previously that Sirt1 in the ARC regulates, at the central level, the thyroid axis via its actions on several components of the central melanocortin system (36,40).…”

Section: Discussionmentioning

confidence: 96%

The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats

Toorie

Cyr

Steger

et al. 2016

Journal of Biological Chemistry

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Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamicpituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamicpituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH.Since its discovery in 1981 (1), corticotropin-releasing hormone (CRH) 2 has been demonstrated to be involved in mediating various physiological processes, including those involved in organismal homeostasis. Renowned for its critical role in mediating the stress response (2), CRH functions to regulate metabolic, immunologic, and homeostatic changes both basally and under various pathologic conditions (3-5). CRH heterogeneously expresses in the periphery and the brain with high expression in the hypothalamic paraventricular nucleus (PVN) (6 -8). Arginine vasopressin (AVP) is also produced in the PVN and acts to synergize CRH actions. It is the CRH that is produced in the medial parvocellular division of the PVN that functions as the central regulator of the HPA axis (9). Levels of bioactive CRH are dependent on the post-translational processing of its precursor pro-CRH. Prohormone posttranslational processing is the mechanism by which all peptide hormones become biologically active (10, 11). In rodents and humans, aberrations in prohormone processing results in deleterious health consequences, including metabolic dysfunctions (12-17). CRH is initially produced as a large inactive precursor, preproCRH, that is made of 196 amino acids (18,19). After cleavage of the signal sequence, the prohormone (pro-CRH) enters the lumen of the rough endoplasmic reticulum and is routed to the trans-Golgi network where it undergoes enzymatic post-translational modifications to generate several intermediate forms as well as the bioactive CRH(1-41) peptid...

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Glucocorticoid hormones and energy homeostasis

Cited by 52 publications

References 143 publications

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Atypical Antipsychotic Drug Olanzapine Deregulates Hepatic Lipid Metabolism and Aortic Inflammation and Aggravates Atherosclerosis

Human Glucocorticoid Receptor β Regulates Gluconeogenesis and Inflammation in Mouse Liver

The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats

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