Dataset Information

Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

ABSTRACT:

Aims

to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression.

Subjects and methods

VAT and SAT biopsies were obtained from morbid obese women (body mass index ? 40 kg/m(2)) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR.

Results

CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues.

Conclusions

24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.

SUBMITTER: Gomez-Abellan P

PROVIDER: S-EPMC3519463 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

Gómez-Abellán Purificación P Díez-Noguera Antoni A Madrid Juan A JA Luján Juan A JA Ordovás José M JM Garaulet Marta M

PloS one 20121210 12

<h4>Aims</h4>to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression.<h4>Subjects and methods</h4>VAT and SAT biopsies were obtained from morbid obese women (body mass index ≥ 40 kg/m(2)) (n = 6). In order to investigate rhythmic expressio ...[more]

PMID: 23251369

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Project description:ContextLipophilic plasma glucocorticoids are thought to gain rapid access to intracellular compartments in adipose tissue. In other organs, transport can be regulated in a steroid- and tissue-specific manner. Moreover, 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) generates additional cortisol within adipose.AimThe aim was to measure the rate of exchange of cortisol between plasma and adipose for comparison with rates of intracellular cortisol generation by 11βHSD1.Participants and interventionsWith ethical approval, otherwise healthy females (n = 6) undergoing hysterectomy for benign indications were infused with tracer 9,11,12,12-[(2)H](4)cortisol (d4-cortisol). Adipose biopsies and peripheral venous samples were obtained during surgery after 3.9-5.5 h of infusion. Glucocorticoids were quantified using liquid chromatography tandem mass spectrometry.ResultsIn plasma, d4-cortisol concentrations and appearance rates of cortisol and d3-cortisol (reflecting 11βHSD1 activity) did not change during surgery. In both omental and sc adipose, cortisol concentrations were lower than in plasma, consistent with differences in corticosteroid binding globulin, and enrichment with d4-cortisol was low (sc, 7.2 ± 0.6%; omental, 7.4 ± 0.7%; vs. plasma, 15.5 ± 1.0%). The rate of accumulation of d4-cortisol in adipose depots was 0.5 ± 0.1 (sc) and 0.4 ± 0.1 (omental) nmol/kg · h, and the proportion of intraadipose cortisol replaced each hour only 10.7 ± 1.0 and 10.4 ± 0.7%, respectively. The contribution of 11βHSD1 to this turnover could not be quantified because very little substrate d3-cortisone accumulated in adipose during infusion.ConclusionsSlow turnover of the adipose glucocorticoid pool suggests that rapid acute fluctuations in circulating cortisol are not reflected in adipose, so that 11βHSD1 activity (previously estimated to generate 9 nmol cortisol/kg · h in sc adipose) may play a relatively important role in modulating activation of glucocorticoid receptors.

Project description:Background:Feed accounts for up to 75% of costs in beef production systems, thus any improvement in feed efficiency (FE) will benefit the profitability of this enterprise. Residual feed intake (RFI) is a measure of FE that is independent of level of production. Adipose tissue (AT) is a major endocrine organ and the primary metabolic energy reservoir. It modulates a variety of processes related to FE such as lipid metabolism and glucose homeostasis and thus measures of inter-animal variation in adiposity are frequently included in the calculation of the RFI index. The aim of this study was to determine the effect of phenotypic RFI status and gender on the expression of key candidate genes related to processes involved in energy metabolism within AT. Dry matter intake (DMI) and average daily gain (ADG) were measured over a period of 70 d for 52 purebred Simmental heifers (n?=?24) and bulls (n?=?28) with an initial BW±SD of 372±39.6 kg and 387±50.6 kg, respectively. Residual feed intake was calculated and animals were ranked within gender by RFI into high (inefficient; n?=?9 heifers and n?=?8 bulls) and low (efficient; n?=?9 heifers and n?=?8 bulls) groups. Results:Average daily gain ±SD and daily DMI ±SD for heifers and bulls were 1.2±0.4 kg and 9.1±0.5 kg, and 1.8±0.3 kg and 9.5±1 kg respectively. High RFI heifers and bulls consumed 10% and 15% more (P?<?0.05) than their low RFI counterparts, respectively. Heifers had a higher expression of all genes measured than bulls (P?<?0.05). A gender × RFI interaction was detected for HMGCS2(P?<?0.05) in which high RFI bulls tended to have lower expression of HMGCS2 than low RFI bulls (P?<?0.1), whereas high RFI heifers had higher expression than low RFI heifers (P?<?0.05) and high RFI bulls (P?<?0.05). SLC2A4 expression was consistently higher in subcutaneous AT of low RFI animals across gender. Conclusion:The findings of this study indicate that low RFI cattle exhibit upregulation of the molecular mechanisms governing glucose metabolism in adipose tissue, in particular, glucose clearance. The decreased expression of SLC2A4 in the inefficient cattle may result in less efficient glucose metabolism in these animals. We conclude that SLC2A4 may be a potential biomarker for RFI in cattle.

Dataset Information

Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

Aims

Subjects and methods

Results

Conclusions

Publications

Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures.

Similar Datasets

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