The interaction between central and peripheral clocks in the regulation of white adipose function

The mammalian circadian timing system consists of a central pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN) and peripheral oscillators found in most tissues of the body – including adipose tissues. Project 10 characterizes the interaction between SCN and adipose clocks in the regulation of adipocyte physiology.

We have previously shown self-sustained molecular circadian rhythms in several types of adipose tissues (Diabetes 2013 Dec;62(12):4154-64) Moreover, lipid mobilization and secretion of several adipokines are regulated in a circadian fashion. We have developed a genetic mouse model with tissue-specific disruption of the SCN clock (J Biol Rhythms. 2011 Oct;26(5):379-89) allowing us to study peripheral physiology in the absence of a central circadian pacemaker in vivo. In parallel we have established experimental paradigms to study human adipose clock function by comparing biopsies with explant cultures.

This project will provide thesis projects for one PhD student for the animal (supervised by HO) and one MD student for the human studies (supervised by SMS). Experimental techniques include metabolic characterization of mice, microarray analysis, pPCR, immune assays, explant cultures, luciferase measurements etc.

Fat explant
Rhythmic Luciferase measurement of fat pads

Publications

Meyer-Kova, J., Kolbe, I., Ehrhardt, L., Leliavski, A., Husse, J., Salinas, G., Lingner, T., Tsang, A. H., Barclay, J. L., and Oster, H.: Hepatic gene therapy rescues high-fat diet responses in circadian Clock mutant mice. Mol Metab, vol. 6, pp. 512-523, 2017, doi: 10.1016/j.molmet.2017.03.008

Kiehn, J., Tsang, A. H., Heyde, I., Leinweber, B., Kolbe, I., Leliavski, A., and Oster, H.: Circadian Rhythms in Adipose Tissue Physiology. Compr Physiol, vol. 7(2), pp. 383-427, 2017, doi: 10.1002/cphy.c160017 

Kolbe, I., Husse, J., Salinas, G., Lingner, T., Astiz, M., and Oster, H.: The SCN Clock Governs Circadian Transcription Rhythms in Murine Epididymal White Adipose Tissue. J Biol Rhythms, vol. 31(6), pp. 577-587, 2016, doi: 10.1177/0748730416666170 

Kolbe, I., Dumbell, R., and Oster, H.: Circadian clocks and the interaction between stress axix and adipose function. Int J Endocrinol, vol. 2015, , 2015, doi: 10.1155/2015/693204 

Anthony, T., Kolbe, I., Seemann, J., and Oster, H.: Interaction of circadian and stress systems in the regulation of adipose physiology. Horm Mol Biol Clin Investig, vol. 19(2), pp. 103-15, 2014, doi: 10.1515/hmbci-2014-0020