Expression of Zinc finger of the cerebellum 1 suggests a possible role in development and/or function of brown adipose tissue

The Royal Society (ME 2012) (2012) Proc Physiol Soc 29, C02 and PC02

Research Symposium: Expression of Zinc finger of the cerebellum 1 suggests a possible role in development and/or function of brown adipose tissue

J. de Jong1, T. B. Waldén2, J. A. Timmons3, N. Petrovic1, I. R. Hansen1, B. Cannon1, J. Nedergaard1

1. Physiology, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. 2. Medical Cell Biology, Uppsala University, Uppsala, Sweden. 3. School of Sports, Exercise and Health Sciences, Loughborough University, Leicestershire, United Kingdom.

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Introduction – Since the discovery of brown adipose tissue in adult humans, the interest in brown adipocyte development and function has gained great interest. Whereas white adipocytes have the capacity to store energy in the form of triglycerides, brown adipocytes are able to use fatty acids as fuel to produce heat. It is of great interest to study which factors contribute to these different functions. Candidates for such genes could be found among those that are differentially expressed between brown and white adipocytes. One such a gene is Zic1 (Zinc finger of the cerebellum 1), which is found selectively in brown adipose tissue. Methods – Male NMRI mice were kept at either 30°C, room temperature or 4°C for 3 weeks starting at 6 weeks of age. Mice were euthanized and adipose tissues were analyzed for gene expression. For primary cultures, male NMRI mice (3-4 weeks old, kept at room temperature) were euthanized and adipose depots were collected and prepared for culture. Results – In different adipose depots analyzed (brown, white and brite,) Zic1 expression is clearly restricted to brown adipose depots. Its expression was not detectable in white and brite adipose depots (Fig. 1a). This restriction to brown adipocytes is maintained in primary adipose cultures. Both in undifferentiated brown preadipocytes and differentiated brown adipocytes Zic1 expression can be detected, whereas it is absent in cultured epididymal (pre)adipocytes (Fig. 1b). Results obtained in brown primary cultures also indicate that Zic1 expression is (negatively) regulated by treatment with the PPARγ-agonist rosiglitazone (Fig .1c). Zic1 expression analysis in interscapular brown adipose tissue does not seem to be affected by diet or temperature (Fig. 2a and 2b). In Zic1 knockdown experiments in primary brown adipose cultures, Ucp1 expression induced by acute norepinephrine treatment is blunted when Zic1 is knocked down (Fig. 2c). Conclusions – Zic1 clearly shows selective brown adipose tissue expression compared to other adipose depots suggesting a possible role in the development or function of brown adipose tissue. The blunted Ucp1 expression upon knockdown of Zic1 in brown adipose culture suggests a functional role for Zic1 in regulation of Ucp1 expression downstream of norepinephrine signaling. Together, these findings ask for follow-up experimental investigation of Zic1 as a functional player in the development and or function of brown adipose tissue.



Where applicable, experiments conform with Society ethical requirements.

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