Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo.
We have inactivated the Repin1 gene in adipose tissue (iARep−/−) at an age of 4 weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice. Furthermore, we differentiated human primary adipocytes derived from subcutaneous AT in vitro and knocked down REPIN1 using siRNA technique to measure glycerol release.
Conditional Repin1 inactivation results in decreased AT mass, smaller adipocytes in both, subcutaneous and epigonadal AT compared to controls. Compared to controls, iARep−/− mice were more insulin sensitive, had better glucose tolerance and lower LDL-, HDL- and total cholesterol. Significantly lower AT expression of the Repin1 target genes Cd36 and Lcn2 may contribute to the phenotype of iARep−/− mice. Knockdown of REPIN1 in human in vitro differentiated adipocytes revealed an increased glycerol release.
In conclusion, deficiency of Repin1 in AT causes alterations in AT morphology and function, which may underlay lower body weight and improved parameters of insulin sensitivity, glucose and lipid metabolism.
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We would like to thank Viola Döbel, Eva Böge, Daniela Kern and Susan Berthold of University of Leipzig for technical assistance. We also want to thank Prof Dr Stefan Offermanns and Dr Antonia Sassmann from Max-Planck-Institute for Heart and Lung Research in Bad Nauheim, Germany, for providing Adipoq–Cre+/− mice. This work was supported by the research group ‘SFB1052/2’, B1 (to MB); B4 (to NK) funded by Deutsche Forschungsgemeinschaft and supported by the Federal Ministry of Education and Research (BMBF), Germany, IFB AdiposityDiseases FKZ: 01EO1501 (N. Klöting), DZD (82DZD00601), DDG (934300-003), by the Helmholtz Alliance ICEMED—Imaging and Curing Environmental Metabolic Diseases, through the Initiative and Networking Fund of the Helmholtz Association, the Swedish Research Council, The Swedish Diabetes Foundation, CIMED, the Diabetes Theme Center at Karolinska Institutet, the Stockholm County Council and the Novo Nordisk Foundation.
The authors declare no conflict of interest.
Supplementary Information accompanies this paper on International Journal of Obesity website
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