Glucocorticoids, metabolism and metabolic diseases

Vegiopoulos, Alexandros; Herzig, Stephan

doi:10.1016/j.mce.2007.05.015

Cited by 441 publications

(406 citation statements)

References 282 publications

(294 reference statements)

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“…In this regard, preliminary data show a 2-fold increase in plasma glucocorticoid levels in 21-day-old ACBP Ϫ/Ϫ mice, which may contribute to the induction of hepatic TAG accumulation because glucocorticoids are known to induce TAG accumulation in the liver ((71-73) and reviewed in Ref. 74). The recent report from Vock et al (28) showing that knockdown of ACBP in HepG2 leads to a decreased expression of SREBP target genes suggests that the suppression of SREBP activity in the liver of ACBP Ϫ/Ϫ mice at weaning may be caused by ACBP deficiency in the liver per se.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

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The mouse acyl-CoA-binding protein (ACBP) 5 /diazepam binding inhibitor is a 10-kDa intracellular protein consisting of 86 amino acids. It is highly conserved throughout evolution and expressed in all cell types in the eukaryotes investigated (1, 2). This, together with the characteristics of the ACBP promoter (3, 4), implies a housekeeping function of the gene. However, expression levels vary markedly between tissues (5) and in response to different metabolic stimuli (6 -9), thereby indicating that ACBP might perform more specialized functions in some cell types. The ACBP protein binds C 14 -C 22 acyl-CoA esters with high affinity and specificity (10, 11) and has very little or no affinity toward other ligands (11-13). From in vitro studies, ACBP is known to protect acyl-CoA esters from hydrolysis (14 -16) and to relieve acyl-CoA inhibition of a number of enzymes, including long chain acyl-CoA synthetase, acetyl-CoA carboxylase (ACC), adenine nucleotide translocase, fatty acid synthetase (FAS), carnitine palmitoyltransferase, and acyl-CoA:cholesterol acyltransferase (9, 16 -18). In addition, ACBP is known to donate acyl-CoA esters to phospholipid, glycerolipid, and cholesteryl ester (CE) synthesis (14, 18 -21). Finally, proteolytic products of secreted ACBP have been shown to have signaling functions in Dictyostelium as well as mammalian cells (22). Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23-25).The functions of ACBP in lipid metabolism have been further studied in different mammalian cell culture systems and animal models by both knockdown strategies and overexpression of the protein. It has been reported that knockdown of ACBP by small interfering RNA causes growth arrest and lethality in three different mammalian cell lines (26); however, data from our laboratory show that ACBP can be knocked down in many different cell systems without affecting growth and survival (27). 6 Recently, knockdown of ACBP in HepG2 cells was shown to suppress the expression of a number of genes involved in lipid biosynthesis and lead to decreased levels of saturated and monounsaturated fatty acids (28). In 3T3-L1 preadipocytes, knockdown of ACBP caused a mild impairment of adipocyte differentiation and accumulation of triacylglycerol (TAG) (27), whereas overexpression of ACBP in McA-RH7777 rat hepatoma cells resulted in increased intracellular TAG accumulation (29). Overexpression of ACBP in transgenic mice resulted in accumulation of different lipid classes, including TAG in the liver (30). These results suggest *

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Section: Discussionmentioning

confidence: 99%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

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“…G lucocorticoids are steroid hormones produced by the adrenal cortex that have diverse effects on a variety of physiological processes including carbohydrate, lipid, and protein metabolism, immune-regulation, bone homeostasis, and developmental processes (Barnes, 1998;Vegiopoulos and Herzig, 2007). The properties of glucocorticoids in regulating the immune system are exploited clinically with numerous synthetic corticosteroids (CS) that are used as antiinflammatory and immunosuppressive agents (Barnes, 1998;Swartz and Dluhy, 1978).…”

Section: Introductionmentioning

confidence: 99%

Tandem Analysis of Transcriptome and Proteome Changes after a Single Dose of Corticosteroid: A Systems Approach to Liver Function in Pharmacogenomics

Kamisoglu

Sukumaran

Nouri-Nigjeh

et al. 2015

OMICS: A Journal of Integrative Biology

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Corticosteroids (CS) such as methylprednisolone (MPL) affect almost all liver functions through multiple mechanisms of action, and long-term use results in dysregulation causing diverse side effects. The complexity of involved molecular mechanisms necessitates a systems approach. Integration of information from the transcriptomic and proteomic responses has potential to provide deeper insights into CS actions. The present report describes the tandem analysis of rich time-series transcriptomic and proteomic data in rat liver after a single dose of MPL. Hierarchical clustering of the common genes represented in both mRNA and protein datasets displayed two dominant patterns. One of these patterns exhibited complementary mRNA and protein expression profiles indicating that MPL affected the regulation of these genes at the transcriptional level. Some of the classic pharmacodynamic markers for CS actions, including tyrosine aminotransferase (TAT), were among this group, together with genes encoding urea cycle enzymes and ribosomal proteins. The other pattern was rather unexpected. For this group of genes, MPL had distinctly observable effects at the protein expression level, although a change in the reverse direction occurred at the transcriptional level. These genes were functionally associated with metabolic processes that might be essential to elucidate side effects of MPL on liver, most importantly including modulation of oxidative stress, fatty acid oxidation, and bile acid biosynthesis. Furthermore, profiling of gene and protein expression data was also done independently of one another by a two-way sequential approach. Prominent temporal shifts in expression and relevant cellular functions were described together with the assessment of changes in the complementary side.

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“…The GR ␣ and ␤ isoforms have been the most studied. The GR␣ is a hormone-activated transcription factor that controls many physiological processes, extending from apoptosis, glucose metabolism to lung development (9,10). The GR␤ isoform, however, lacks helix 12 of the C terminus in the ligand-binding domain and cannot bind GCs (11).…”

mentioning

confidence: 99%

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

Stechschulte

Wuescher

Marino

et al. 2014

Journal of Biological Chemistry

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Background:The glucocorticoid receptor ␤ (GR␤) is a positive regulator of growth. Results: GR␤ suppression of PTEN resulted in enhanced phosphorylation of Akt and growth. Conclusion: GR␤ enhances insulin-induced proliferation by suppressing PTEN and activating Akt1. Significance: GR␤ suppression of PTEN indicates that it has an important role in growth factor signaling and potentially cancer.

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Glucocorticoids, metabolism and metabolic diseases

Cited by 441 publications

References 282 publications

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Tandem Analysis of Transcriptome and Proteome Changes after a Single Dose of Corticosteroid: A Systems Approach to Liver Function in Pharmacogenomics

Glucocorticoid Receptor β Stimulates Akt1 Growth Pathway by Attenuation of PTEN

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