Endocrine Abstracts

Organismal metabolic homeostasis is normally accomplished by the physiological functions of several metabolic tissues, including liver, muscle, and fat. The endocrine system coordinates organismal metabolic homeostasis via hormones, such as insulin and glucocorticoids, that act on metabolic tissues to partition nutrients within a physiological range. Metabolic diseases, such as obesity and diabetes, ensue when these homeostatic systems fail. Normal metabolic physiology also displays circadian rhythmicity that likely evolved to anticipate recurrent, daily shifts between periods of inactivity/fasting and activity/feeding. The nuclear heme receptors Rev-erbα and β are potent transcription repressors whose expression in peripheral tissues is highly circadian. The Rev-erbs function as redundant components of the molecular clock as well as direct regulators of circadian gene expression. In liver, Rev-erbs rhythmically recruit the NCoR-HDAC3 corepressor complex to target genes across the genome, generating an oscillating epigenome and controlling circadian hepatic lipid metabolism. In brown adipose tissue, Rev-erbα expression is antiphase to the body temperature rhythm, and its repression of uncoupling protein 1 contributes to the daily nadir of body temperature as well as to a physiological rhythm of tolerance to cold ambient temperature. The role of oscillating Rev-erb expression in the integrated physiology of circadian rhythms and metabolism will be discussed.