TY - JOUR
T1 - Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling
AU - Natarajan, Gopalakrishnan
AU - Perriotte-Olson, Curtis
AU - Bhinderwala, Fatema
AU - Powers, Robert
AU - Desouza, Cyrus V.
AU - Talmon, Geoffrey A.
AU - Yuhang, Jiang
AU - Zimmerman, Matthew C.
AU - Kabanov, Alexander V.
AU - Saraswathi, Viswanathan
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10
Y1 - 2017/10
N2 - Evidence suggests that superoxide dismutase 1 (SOD1) promotes glucose vs lipid metabolism depending on the diet type. We recently reported that nanoformulated SOD1 (Nano) improved lipid metabolism without altering glucose homeostasis in high-fat (HF) diet-fed mice. Here, we sought to determine the effects and potential mechanisms of Nano in modulating glucose and lipid homeostasis in mice fed a normal chow diet (CD) vs HF diet. Mice were fed a CD or a HF diet (45%) for 10 wk and injected with Nano once every 2 days for 15 days. The fasting glucose level was lower (P < 0.05) in CD + Nano-treated mice compared to control. Conversely, blood glucose was not altered but serum triglycerides were lower in HF + Nano-treated mice. Genes involved in fatty acid synthesis were reduced by Nano in the skeletal muscle of CD but not of HF diet-fed mice. Adenosine monophosphate-activated protein kinase (AMPK), which promotes both glucose and lipid metabolism depending on the fuel availability, is activated by Nano in CD-fed mice. Moreover, Nano increased phosphorylation of ACC, a downstream target of AMPK, in both CD and HF diet-fed mice. Nano increased mitochondrial respiration in C2C12 myocytes in the presence of glucose or fatty acid, and this effect is inhibited by Compound C, an AMPK inhibitor. Our data suggest that Nano promotes glucose and lipid metabolism in CD and HF diet–fed mice, respectively, and this effect is mediated partly via AMPK signaling.
AB - Evidence suggests that superoxide dismutase 1 (SOD1) promotes glucose vs lipid metabolism depending on the diet type. We recently reported that nanoformulated SOD1 (Nano) improved lipid metabolism without altering glucose homeostasis in high-fat (HF) diet-fed mice. Here, we sought to determine the effects and potential mechanisms of Nano in modulating glucose and lipid homeostasis in mice fed a normal chow diet (CD) vs HF diet. Mice were fed a CD or a HF diet (45%) for 10 wk and injected with Nano once every 2 days for 15 days. The fasting glucose level was lower (P < 0.05) in CD + Nano-treated mice compared to control. Conversely, blood glucose was not altered but serum triglycerides were lower in HF + Nano-treated mice. Genes involved in fatty acid synthesis were reduced by Nano in the skeletal muscle of CD but not of HF diet-fed mice. Adenosine monophosphate-activated protein kinase (AMPK), which promotes both glucose and lipid metabolism depending on the fuel availability, is activated by Nano in CD-fed mice. Moreover, Nano increased phosphorylation of ACC, a downstream target of AMPK, in both CD and HF diet-fed mice. Nano increased mitochondrial respiration in C2C12 myocytes in the presence of glucose or fatty acid, and this effect is inhibited by Compound C, an AMPK inhibitor. Our data suggest that Nano promotes glucose and lipid metabolism in CD and HF diet–fed mice, respectively, and this effect is mediated partly via AMPK signaling.
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U2 - 10.1016/j.trsl.2017.08.002
DO - 10.1016/j.trsl.2017.08.002
M3 - Article
C2 - 28867395
AN - SCOPUS:85028714777
SN - 1931-5244
VL - 188
SP - 10
EP - 26
JO - Translational Research
JF - Translational Research
ER -