Journal Article

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

Foulkes, Nicholas S, Garaulet, Marta, Luján, Juan A, Madrid, Juan A, Díez-Noguera, Antoni, Gómez-Abellán, Purificación, Ordovás, José M

2012

Overview

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. 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Abdomen / Adipose tissue / Adipose Tissue - drug effects / Adipose Tissue - metabolism / Adult / ARNTL Transcription Factors - genetics / ARNTL Transcription Factors - metabolism / Biological clocks / Biology / Biopsy / BMAL1 protein / Body fat / Body mass / Body Mass Index / Body size / Cell cycle / Cholesterol / Circadian rhythm / Circadian Rhythm - drug effects / Circadian Rhythm - genetics / Circadian rhythms / CLOCK Proteins - genetics / CLOCK Proteins - metabolism / Comparative analysis / Dexamethasone / Dexamethasone - pharmacology / Diabetes / Explants / Exposure / Female / Gastrointestinal surgery / Gene expression / Gene Expression Regulation - drug effects / Genes / Genetic research / Genomics / Glucocorticoids / Glucocorticoids - pharmacology / Hormone replacement therapy / Humans / Medicine / messenger RNA / Metabolism / Middle Aged / Nutrition research / Obesity / Obesity, Morbid - genetics / Obesity, Morbid - metabolism / Period 2 protein / Period Circadian Proteins - genetics / Period Circadian Proteins - metabolism / Physiology / quantitative polymerase chain reaction / reverse transcriptase polymerase chain reaction / RNA, Messenger - genetics / RNA, Messenger - metabolism / Rodents / Steroids (Organic compounds) / Studies / Tissues / Weight control / women