In the core TTFL, transcription factors CLOCK and ARNTL (also known as BMAL1) stimulate transcription of three Period ( Per) and two Cryptochrome ( Cry) genes. Misalignment of human clocks with each other and the environment is believed to be a major contributor to obesity and related pathologies associated with shift work 4, 5.Īt the molecular level, circadian clocks are formed from a set of inter-locking transcriptional translational feedback loops (TTFLs). Circadian disruption causes abnormal metabolic physiology 3. This system is comprised of a central ‘master’ clock in the hypothalamic suprachiasmatic nuclei and an integrated network of circadian clocks present in all major tissues within the body 2.
Many aspects of mammalian metabolism exhibit daily variation driven in part by an endogenous circadian timing system 1. In summary, in vivo circadian rhythms exist in multiple adipose metabolic pathways, including those involved in lipid metabolism, and core aspects of cellular biochemistry. In silico pathway analysis further indicated circadian regulation of lipid and nucleic acid metabolism it also predicted circadian variation in key metabolic pathways such as the citric acid cycle and branched chain amino acid degradation. Morning-peaking transcripts associated with regulation of gene expression, nitrogen compound metabolism, and nucleic acid biology evening-peaking transcripts associated with organic acid metabolism, cofactor metabolism and redox activity. There was only partial overlap of our rhythmic transcripts with published animal adipose and human blood transcriptome data. We identified 837 transcripts exhibiting circadian expression profiles (2% of 41619 transcript targeting probes on the array), with clear separation of transcripts peaking in the morning (258 probes) and evening (579 probes). Five biopsies per participant were taken at six-hourly intervals for microarray analysis and in silico integrative metabolic modelling. Subcutaneous adipose tissue was taken from seven healthy males under highly controlled ‘constant routine’ conditions. Here we reveal circadian rhythms in the transcriptome and metabolic pathways of human white adipose tissue.
#Api reverb lp csv serial
Studying circadian rhythms in most human tissues is hampered by difficulty in collecting serial samples.
Subcutaneous adipose tissue was taken from seven healthy males under highly controlled 'constant routine' conditions.
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