Endocrine Abstracts (2011) 26 P332

Effects of food, hormones and autonomic nervous activity on rhythmic expression of clock genes and metabolic genes in rat white adipose tissue

R van der Spek1, L Kervezee1, S La Fleur1, E Fliers1 & A Kalsbeek1,2

1Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; 2Netherlands Institute for Neuroscience, Hypothalamic Integration Mechanisms, Amsterdam, The Netherlands.

Background: Shift workers and rodents with clock gene mutations show increased risk of metabolic syndrome and type 2 diabetes (T2DM). Conversely, obesity and T2DM are related to circadian disturbances in humans and rodents. The circadian release of adipokines from white adipose tissue (WAT) plays a pivotal role in energy metabolism. Its regulatory mechanism is unclear at present.

Aim: To determine the daily expression patterns of genes involved in circadian and metabolic pathways in different compartments of rat WAT. Subsequently, to investigate effects of scheduled feeding on these expression patterns.

Methods: Experiment 1: 64♂ Wistar rats were killed at 8 timepoints during the 12 h light:12 h darkness cycle. Blood was collected, perirenal-(prWAT), subcutaneous-(sWAT), epididymal-(eWAT) and mesenteric WAT (mWAT) were dissected and RT-qPCR was performed.

Experiment 2: rats (n=9 per ZT) were entrained to a six-meals-a-day feeding schedule. Each meal consisted of a 10 min feeding opportunity once every 4 h. Animals remained on this schedule for 4 weeks before they were killed at ZT2 and ZT14. Controls were fed ad libitum (n=3 per ZT). Blood was collected, prWAT and sWAT were dissected and RT-qPCR was performed.

Results: Experiment 1: in intact rats, circadian genes as well as part of the metabolic genes, showed distinct day/night rhythms in prWAT and sWAT. Only minor differences between prWAT and sWAT were found.

Experiment 2: day/night rhythms of most circadian genes were attenuated in absence of the day/night rhythm in feeding activity. In metabolic genes no significant effect of feeding regimen was found. Overall, effects were more pronounced in prWAT as compared to sWAT.

Conclusion: The clock gene rhythm amplitude in prWAT is partly dependent on rhythmic food intake. Additionally, hormones and nervous input likely contribute to fine-tuning of the rhythmic expression of clock- and metabolic genes in WAT and are subject of our future studies.

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