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Silencing Fatty Acid Binding Protein‐4 Through Percutaneous Retro‐orbital Injections Attenuates Inflammation in ApoE−/− Mice Liver
Author(s) -
Prathipati Priyanka,
RodriguezAguayo Cristian,
Walton Brian,
Sood Anil,
Lopez Gabriel Berestein
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.505.23
Subject(s) - gene silencing , inflammation , steatosis , medicine , fatty acid binding protein , western blot , oil red o , fatty liver , endocrinology , pathology , chemistry , biochemistry , adipose tissue , gene , disease , adipogenesis
Background Fatty acid binding protein‐4 (FABP4) is a lipid chaperon is an important regulator of atherosclerosis and inflammation. We hypothesize that silencing FABP4 could be a novel therapeutic treatment for atherosclerosis, in turn liver inflammation. Hence a liposomal small interfering RNA (siRNA) delivery system to silence FABP4 was developed. Methods Male ApoE mice (N=16) were fed high fat diet from 6 weeks of age until 12–16 weeks. At 11 weeks of age, the mice were injected with 0.1ml (500µg/ml) of FABP4/control siRNA liposomes tagged with fluorescent Qdot (QD) 625. The injections were administered through percutaneous retro‐orbital route twice a week for four consecutive weeks. Starting in the 12 th week, two mice from each group were sacrificed every week. Aortas, serum and livers were collected at the time of sacrifice, parts of these organs were stored in formalin and processed for paraffin sections and part of them were flash frozen for protein analysis. FABP4 in aortas and livers along with the pro‐inflammatory markers (IL‐6) in livers were analyzed by western blot and immunohistochemistry. This investigates the effect of FABP4 siRNA liposomes on atherosclerosis and inflammation in liver. Results Silencing FABP4 in ApoE mice attenuates the inflammation in liver compared to the control siRNA treatment (Figure). Conclusion Percutaneous retro‐orbital injections of FABP4 siRNA liposomes for four consecutive weeks might help to attenuate liver inflammation in ApoE mice. Effect of FABP4 silencing on liver inflammation Silencing FABP4 attenuated the expression of pro‐inflammatory marker in the livers of ApoE−/− mice. Support or Funding Information This work was supported by Gillson Longenbaugh Foundation (9091‐001‐N‐1 & G2015) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .