scholarly journals Hepatic Glucocorticoid Receptor Plays a Greater Role Than Adipose GR in Metabolic Syndrome Despite Renal Compensation

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4943-4960 ◽  
Author(s):  
Sandip K. Bose ◽  
Irina Hutson ◽  
Charles A. Harris
Keyword(s):  
Metabolic Syndrome ◽  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Kidney Tissue ◽  
Glycogen Metabolism ◽  
Whole Body ◽  
Pcr Analysis ◽  
Compensatory Mechanism ◽  
Key Genes ◽  
Specific Deletion

Exogenous glucocorticoid administration results in hyperglycemia, insulin resistance, hepatic dyslipidemia, and hypertension, a constellation of findings known as Cushing’s syndrome. These effects are mediated by the glucocorticoid receptor (GR). Because GR activation in liver and adipose has been implicated in metabolic syndrome (MS), we wanted to determine the role of GR in these tissues in the development of MS. Because GR knockout (KO) mice (whole-body KO) exhibit perinatal lethality due to respiratory failure, we generated tissue-specific (liver or adipose) GRKO mice using cre-lox technology. Real-time PCR analysis of liver mRNA from dexamethasone-treated wildtype (WT) and liver GRKO mice indicated that hepatic GR regulates the expression of key genes involved in gluconeogenesis and glycogen metabolism. Interestingly, we have observed that liver-specific deletion of GR resulted in a significant increase in mRNA expression of key genes involved in gluconeogenesis and glycogen metabolism in kidney tissue, indicating a compensatory mechanism to maintain glucose homeostasis. We have also observed that GR plays an important role in regulating the mRNA expression of key genes involved in lipid metabolism. Liver GRKO mice demonstrated decreased fat mass and liver glycogen content compared with WT mice administered dexamethasone for 2 weeks. Adipose-specific deletion of GR did not alter glucose tolerance or insulin sensitivity of adipose GRKO mice compared with WT mice administrated dexamethasone. This indicates that liver GR might be more important in development of MS in dexamethasone-treated mice, whereas adipose GR plays a little role in these paradigms.

scholarly journals Antiinflammatory Steroid Action in Human Ovarian Surface Epithelial Cells

2004 ◽  
Vol 89 (9) ◽  
pp. 4538-4544 ◽  
Author(s):  
Michael T. Rae ◽  
Deborah Niven ◽  
Hilary O. D. Critchley ◽  
Christopher R. Harlow ◽  
Stephen G. Hillier
Keyword(s):  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Mrna Level ◽  
Inhibitory Effect ◽  
Surface Epithelium ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Cell Monolayers ◽  
Ovarian Surface ◽  
Cox 2

The human ovarian surface epithelium (OSE) is subject to serial injury and repair during ovulation, which is a natural inflammatory event. We asked whether there is a compensatory antiinflammatory component to this process, involving steroid hormones produced locally at the time of ovulation. Quantitative RT-PCR analysis of total RNA from cultured human OSE cell monolayers showed that exposure to proinflammatory IL1α (500 pg/ml) increased mRNA levels of cyclooxygenase-2 (COX-2) (P < 0.01) at 48 h. The COX-2 mRNA response to IL1α was associated with an approximate 18-fold (P < 0.01) increase in mRNA levels of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), encoding the steroid dehydrogenase that reversibly reduces cortisone to antiinflammatory cortisol. Addition of cortisol to OSE cell culture medium dose-dependently suppressed the COX-2 mRNA response to IL1α (P < 0.01) but reciprocally enhanced the 11βHSD1 mRNA response (P < 0.05), with both effects strongest at 1 μm cortisol. Presence of glucocorticoid receptor-α mRNA and protein was established in OSE cell monolayers and treatment with IL1α shown to significantly up-regulate the glucocorticoid receptor-α mRNA level (P < 0.05). Glucocorticoid receptor antagonist (RU486, 10 μm) fully reversed the inhibitory effect of 1 μm cortisol on IL1α-stimulated COX-2 mRNA expression. Progesterone also suppressed IL1α-induced COX-2 mRNA expression but had no significant effect on IL1α-stimulated 11βHSD1 expression. These data provide direct evidence for antiinflammatory actions of cortisol and progesterone in human OSE cells.

459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 459-P
Author(s):  
LEIGH GOEDEKE ◽  
NOEMI ROTLLAN ◽  
KESHIA TOUSSAINT ◽  
ALI NASIRI ◽  
XINBO ZHANG ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Mouse Model ◽  
Whole Body ◽  
Mitochondrial Uncoupling

Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-α-amidating mono-oxygenase mRNA expression in bovine luteal and granulosa cells

2013 ◽  
Vol 16 (2) ◽  
pp. 231-239
Author(s):  
A. Ziolkowska ◽  
J. Mlynarczuk ◽  
J. Kotwica
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Hormone Secretion ◽  
Oestrous Cycle ◽  
Luteal Cells ◽  
Ru 486 ◽  
Ovarian Cells ◽  
Key Genes ◽  
Ovary Function

Abstract Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine granulosa and luteal cells, but the molecular mechanisms of cortisol action remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and 11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1x10-5, 1x10-7 M). After testing cell viability and hormone secretion (OT, progesterone, estradiol), we studied the effect of cortisol on mRNA expression for precursor of OT (NP-I/OT) and peptidyl glycine-α-amidating mono-oxygenase (PGA). The influence of RU 486 (1x10-5 M), a progesterone receptor blocker and inhibitor of the glucocorticosteroid receptor (GR), on the expression for both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and PGA in both types of cells. These data suggest that cortisol affects OT synthesis and secretion in bovine ovarian cells, by acting on the expression of key genes, that may impair ovary function.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

scholarly journals Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 319
Author(s):  
Oliver D. John ◽  
Peter Mouatt ◽  
Sunil K. Panchal ◽  
Lindsay Brown
Keyword(s):  
Metabolic Syndrome ◽  
Inflammatory Cells ◽  
Left Ventricular ◽  
Metabolic Changes ◽  
Abdominal Circumference ◽  
Whole Body ◽  
Garcinia Mangostana ◽  
Tropical Fruit ◽  
Cardiovascular Parameters ◽  
Left Ventricular Stiffness

The pulp of the purple mangosteen, Garcinia mangostana, is a popular tropical fruit but the rind containing xanthones such as α-mangostin together with procyanidins and anthocyanidins is usually discarded as waste. However, this rind has been used in South-East Asia for diarrhoea, dysentery, skin infections and wounds. As xanthones have reported anti-inflammatory and antioxidant responses, this study has determined the bioactive compounds and evaluated the effects of G. mangostana rind on physiological, metabolic, liver and cardiovascular parameters in rats with diet-induced metabolic syndrome. Rats fed a diet with increased simple sugars and saturated fats developed obesity, hypertension, increased left ventricular stiffness, dyslipidaemia and fatty liver. Administration of G. mangostana rind as 5% of the food to rats with diet-induced metabolic syndrome gave a dose of 168 mg/kg/day α-mangostin, 355 mg/kg/day procyanidins, 3.9 mg/kg/day anthocyanins and 11.8 mg/kg/day hydroxycitric acid for 8 weeks which reduced body weight and attenuated physiological and metabolic changes in rats including decreased abdominal fat deposition, decreased abdominal circumference and whole-body fat mass, improved liver structure and function and improved cardiovascular parameters such as systolic blood pressure, left ventricular stiffness and endothelial function. These responses were associated with decreased infiltration of inflammatory cells, decreased deposition of collagen in both heart and liver and decreased mean adipocyte size in retroperitoneal adipose tissues. We conclude that, in rats with diet-induced metabolic syndrome, chronic intake of G. mangostana rind decreased infiltration of inflammatory cells which decreased physiological, metabolic, liver and cardiovascular symptoms.

scholarly journals Whole Body Vibration Exercises and the Improvement of the Flexibility in Patient with Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Danúbia da Cunha Sá-Caputo ◽  
Pedro Ronikeili-Costa ◽  
Rafaelle Pacheco Carvalho-Lima ◽  
Luciana Camargo Bernardo ◽  
Milena Oliveira Bravo-Monteiro ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Muscle Power ◽  
Whole Body Vibration ◽  
Whole Body ◽  
Mineral Density ◽  
Level Of Evidence ◽  
Body Vibration ◽  
Pubmed Database ◽  
Number Of Publications

Vibrations produced in oscillating/vibratory platform generate whole body vibration (WBV) exercises, which are important in sports, as well as in treating diseases, promoting rehabilitation, and improving the quality of life. WBV exercises relevantly increase the muscle strength, muscle power, and the bone mineral density, as well as improving the postural control, the balance, and the gait. An important number of publications are found in the PubMed database with the keyword “flexibility” and eight of the analyzed papers involving WBV and flexibility reached a level of evidence II. The biggest distance between the third finger of the hand to the floor (DBTFF) of a patient with metabolic syndrome (MS) was found before the first session and was considered to be 100%. The percentages to the other measurements in the different sessions were determined to be related to the 100%. It is possible to see an immediate improvement after each session with a decrease of the %DBTFF. As the presence of MS is associated with poorer physical performance, a simple and safe protocol using WBV exercises promoted an improvement of the flexibility in a patient with MS.

Quantitative RT-PCR analysis of MMP and TIMP MRNA expression in correlation to liver histology in patients with chronic hepatitis C

2000 ◽  
Vol 118 (4) ◽  
pp. A1469
Author(s):  
Dirk Michels ◽  
Christian I. Haberkorn ◽  
Burkhard Arndt ◽  
Michael P. Manns
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Mrna Expression ◽  
Chronic Hepatitis C ◽  
Liver Histology ◽  
Pcr Analysis ◽  
Rt Pcr

scholarly journals Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts

2007 ◽  
Vol 195 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Zhen Yang ◽  
Chunming Guo ◽  
Ping Zhu ◽  
Wenjiao Li ◽  
Leslie Myatt ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Promoter Region ◽  
Molecular Mechanisms ◽  
Hydroxysteroid Dehydrogenase ◽  
Dominant Negative ◽  
Forward Induction ◽  
Human Amnion ◽  
Feed Forward

The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which converts cortisone to cortisol. We examined the molecular mechanisms of the feedback effect of cortisol on 11β-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced 11β-HSD1 mRNA expression dose dependently in amnion fibroblasts, which could be completely blocked both by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside and by the glucocorticoid receptor (GR) antagonist RU486, and partially blocked by global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression CMV500 plasmid (AC/EBP) into the cells. Likewise, the induction of the promoter activity by cortisol could also be completely blocked by RU486 and partially by AC/EBP transfection. Progressive 5′ deletion of the 11β-HSD1promoter located the region responsible for cortisol’s induction within −204 bp upstream to the transcription start site. Specific nucleotide mutations of the putative glucocorticoid responsive element or CCAAT in this promoter region attenuated the induction by cortisol. Moreover, chromatin immunoprecipitation assay and electrophoretic mobility shift assay showed that GR and C/EBPα but not C/EBPβ could bind this promoter region upon cortisol stimulation of amnion fibroblasts. In conclusion, we demonstrated that GR and C/EBPα were involved in cortisol-induced 11β-HSD1 mRNA expression via binding to 11β-HSD1 promoter in amnion fibroblasts, which may cast a feed-forward production of cortisol in the fetal membranes at the end of gestation.

Anemic Hypoxemia Reduces Myoblast Proliferation and Muscle Growth in Late Gestation Fetal Sheep

2021 ◽  
Author(s):  
Paul J. Rozance ◽  
Stephanie R Wesolowski ◽  
Sonnet S. Jonker ◽  
Laura D Brown
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Growth ◽  
Late Gestation ◽  
Whole Body ◽  
Myoblast Differentiation ◽  
Fetal Sheep ◽  
Body Protein ◽  
Skeletal Muscle Growth ◽  
Myoblast Proliferation

Fetal skeletal muscle growth requires myoblast proliferation, differentiation, and fusion into myofibers in addition to protein accretion for fiber hypertrophy. Oxygen is an important regulator of this process. Therefore, we hypothesized that fetal anemic hypoxemia would inhibit skeletal muscle growth. Studies were performed in late gestation fetal sheep that were bled to anemic, and therefore hypoxemic, conditions beginning at ~125 days of gestation (term = 148 days) for 9 ± 0 days (n=19) and compared to control fetuses (n=16). A metabolic study was performed on gestational day ~134 to measure fetal protein kinetic rates. Myoblast proliferation and myofiber area were determined in biceps femoris (BF), tibialis anterior (TA), and flexor digitorum superficialis (FDS) muscles. mRNA expression of muscle regulatory factors was determined in BF. Fetal arterial hematocrit and oxygen content were 28% and 52% lower, respectively, in anemic fetuses. Fetal weight and whole-body protein synthesis, breakdown, and accretion rates were not different between groups. Hindlimb length, however, was 7% shorter in anemic fetuses. TA and FDS muscles weighed less and FDS myofiber area was smaller in anemic fetuses compared to controls. The percentage of Pax7+ myoblasts that expressed Ki67 was lower in BF and tended to be lower in FDS from anemic fetuses indicating reduced myoblast proliferation. There was less MYOD and MYF6 mRNA expression in anemic vs. control BF consistent with reduced myoblast differentiation. These results indicate that fetal anemic hypoxemia reduced muscle growth. We speculate that fetal muscle growth may be improved by strategies that increase oxygen availability.

Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis

2021 ◽  
Author(s):  
Shang-Wu Shih ◽  
Jia-Jiun Yan ◽  
Yi-Hsing Wang ◽  
Yi-Ling Tsou ◽  
Ling Chiu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Body Fluid ◽  
Whole Body ◽  
Ionic Homeostasis ◽  
Ion Regulation ◽  
Expression Levels ◽  
Morpholino Knockdown ◽  
Oryzias Melastigma ◽  
Euryhaline Teleost

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that ERRγ2 may play a crucial role in ion uptake. In situ hybridization and immunofluorescence staining showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl- transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl- cotransporter (NCC), the number of NCC ionocytes, Na+/Cl- influxes of ionocytes, and whole-body Na+/Cl- contents. In FW with low Na+ and low Cl-, the expression levels of mRNA for Na+/H+ exchanger 3 (NHE3) and NCC were both decreased in ERRγ2 morphants. Treating embryos with DY131, an agonist of ERRγ, increased the whole-body Na+/Cl- contents and ncc mRNA expression in ERRγ2 morphants. As such, medaka ERRγ2 may control Na+/Cl- uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

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