Abstract
Adipose tissue resident eosinophils (AT-EOS) are thought to play a pivotal role in whole-body energy homeostasis. However, the precise role of, and the mechanisms underlying AT-EOS in the regulation of whole-body energy metabolism remains elusive. This is because of the limitations of rodent models which have been genetically engineered to either produce elevated whole-body eosinophils or knock-out models for this hematopoietic lineage. To determine the function of AT-EOS, we generated a transgenic mouse model overexpressing human eotaxin[AV1] 2 (hEo2), which is an eosinophil specific chemokine, under the control of a fat-specific aP2 promoter, to recruit circulating EOS exclusively into adipose (hEo2tg). Compared to wild type (WT) littermates of both genders, hEo2tg mice displayed a significant increase of AT-EOS in multiple AT depots including, perirenal and subcutaneous white adipose tissue (sWAT). However, EOS were not increased in brown adipose tissue (BAT). When fed a high-fat diet (HFD), hEo2tg mice gained less weight (males weight: 45.5 ±0.7g vs. 51 ±0.4g, P<0.01 hEo2tg vs. WT) and adipose tissue (males %fat: 20.8 ±0.2 vs. 31.7 ±0.6, P<0.01 hEo2tg vs. WT) compared to WT. Transgenic mice showed improved glucose tolerance (GTT) compared to WT (males GTT AUC: 300054±121 vs. 320865 ±920, hEo2tg vs. WT P<0.001). This was accompanied by increased energy expenditure and heat production compared to WT. These phenotypes were equally found in female animals. Moreover, the adipocytes in hEo2tg were smaller in both genders, and the expression of genes involved in fat oxidation in BAT and sWAT was upregulated in hEo2tg mice compared to WT mice. These data suggest that WAT-resident EOS contribute to increased BAT activation, browning of sWAT and to whole-body energy expenditure. Additional studies will be needed to evaluate the molecular mechanism(s) underling the benefits of AT- EOS. Disclosure T. Li: None. W. LeSuer: None. A. Singh: None. J.D. Hernandez: None. X. Zhang: None. D. Jelinek: None. J. Liu: None. A. Vella: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Novo Nordisk Inc. E.A. Jacobsen: None. E. DeFilippis: None. Funding National Center for Advancing Translational Sciences (KL2TR002379)
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
