TY - JOUR
T1 - Nanoparticle-mediated in vitro delivery of E4orf1 to preadipocytes is a clinically relevant delivery system to improve glucose uptake
AU - Feizy, Zahra
AU - Peddibhotla, Swetha
AU - Khan, Shahjalal
AU - Hegde, Vijay
AU - Wang, Shu
AU - Dhurandhar, Nikhil V.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Objective: Impaired glycemic control is a common comorbidity of obesity. E4orf1(E4), an adenovirus-derived protein, reduces the activity of insulin receptor substrate (IRS), yet activates Akt and promotes the membrane translocation of GLUT4, resulting in better glycemic control in mice. To develop a clinically suitable delivery system, here we constructed and tested liposome nanoparticles (NP), to deliver E4 to preadipocytes. Methods: Glutathione-S-transferase (GST)-tagged E4 was encapsulated in Rhodamine-phosphatidylethanolamine (PE)-tagged soy-phosphatidylcholine-NP. The NP were characterized. Preadipocytes were treated with free E4, E4 containing NP (E4 NP) or E4-free NP (void NP). Results: For void and E4 NP, the average size was ~150 and 130 nm, PDI was ~0.25 and 0.27, and Zeta potential was −23 and −25, respectively. The average encapsulation efficiency (EE) was ~50%. Cells treated with E4 showed maximum GST expression and Rhodamine signals at 24 h. The presence of E4 in cells was confirmed at 24, 48, and 72 h. At 72 h after exposure, E4 NP significantly decreased pTyr-IRS, yet increased pAkt protein abundance, membrane translocation of GLUT4, and glucose uptake, compared with cells treated with void NP. Free E4 (without NP) had no effect. Conclusions: NP-mediated delivery of E4 promotes glucose uptake in preadipocytes. The next step is to test the efficacy of this clinically compatible delivery approach in vivo.
AB - Objective: Impaired glycemic control is a common comorbidity of obesity. E4orf1(E4), an adenovirus-derived protein, reduces the activity of insulin receptor substrate (IRS), yet activates Akt and promotes the membrane translocation of GLUT4, resulting in better glycemic control in mice. To develop a clinically suitable delivery system, here we constructed and tested liposome nanoparticles (NP), to deliver E4 to preadipocytes. Methods: Glutathione-S-transferase (GST)-tagged E4 was encapsulated in Rhodamine-phosphatidylethanolamine (PE)-tagged soy-phosphatidylcholine-NP. The NP were characterized. Preadipocytes were treated with free E4, E4 containing NP (E4 NP) or E4-free NP (void NP). Results: For void and E4 NP, the average size was ~150 and 130 nm, PDI was ~0.25 and 0.27, and Zeta potential was −23 and −25, respectively. The average encapsulation efficiency (EE) was ~50%. Cells treated with E4 showed maximum GST expression and Rhodamine signals at 24 h. The presence of E4 in cells was confirmed at 24, 48, and 72 h. At 72 h after exposure, E4 NP significantly decreased pTyr-IRS, yet increased pAkt protein abundance, membrane translocation of GLUT4, and glucose uptake, compared with cells treated with void NP. Free E4 (without NP) had no effect. Conclusions: NP-mediated delivery of E4 promotes glucose uptake in preadipocytes. The next step is to test the efficacy of this clinically compatible delivery approach in vivo.
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U2 - 10.1038/s41366-020-0526-6
DO - 10.1038/s41366-020-0526-6
M3 - Article
C2 - 31965070
AN - SCOPUS:85078298174
SN - 0307-0565
VL - 44
SP - 1607
EP - 1616
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 7
ER -