Nanoformulated Copper/Zinc Superoxide Dismutase Exerts Differential Effects on Glucose versus Lipid Homeostasis Depending on the Diet Composition Possibly via Altered AMPK Signaling

Publication date: Available online 15 August 2017
Source:Translational Research
Author(s): Gopalakrishnan Natarajan, Curtis Perriotte-Olson, Fatema Bhinderwala, Robert Powers, Cyrus V. Desouza, Geoffrey A. Talmon, Jiang Yuhang, Matthew C. Zimmerman, Alexander V. Kabanov, Viswanathan Saraswathi
Evidence suggests that superoxide dismutase 1 (SOD1) promotes glucose versus 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) versus HF diet. Mice were fed a CD or a HF diet (45%) for 10 wk and injected with Nano once every two days for fifteen 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. 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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