Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling

Abstract

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.

Triglyceride is independently correlated with insulin resistance and islet beta cell function: a study in population with different glucose and lipid metabolism states

“…A cross-sectional study showed that serum SOD level negatively correlates with BMI, TG, BG, and carotid artery intima-media thickness [46], in accordance with the present study. Perriotte-Olson et al found that mice fed a high-fat diet and treated with nanoformulated SOD (NanoSOD) showed significant decreases in plasma and liver TG levels [47], and improved glucose and lipid metabolism [48]. The evidence above indicates that SOD plays an important role in glucose and lipid metabolism, and the mechanism of its effect requires further study.…”

Nanoformulation of Brain‐Derived Neurotrophic Factor with Target Receptor‐Triggered‐Release in the Central Nervous System

“…DMEM, 500 ng mL −1 of BDNF, Nano-BDNF ( Z −/+ = 946), or equivalent amount of PEG-PLE polymer in the Nano-BDNF formulation were incubated with the cells for 5 min at 37 °C in serum-free DMEM then moved to ice for 20 min and lysed using radioimmunoprecipitation assay buffer with proteinase and phosphatase inhibitors. Western blot analysis was conducted as reported previously [41] with modifications. Briefly, 10 μg total protein from the cell lysates was loaded in each well of 7.5% Mini-PROTEAN® TGX™ precast gels and run at 150 V for 1 h. Proteins were then transferred to 0.45 μm polyvinylidene difluoride membranes at 500 mA current for 1 h. The membranes were then blocked in either 5% BSA (for detection of phosphorylated TrkB and ERK) or 5% nonfat dry milk (for detection of total TrkB and ERK) for 30 min at RT followed by an overnight incubation at 4 °C with primary antibody.…”

Superoxide Dismutase Administration: A Review of Proposed Human Uses

“…once every two days for 15 days). In particular, SOD administration reduced the levels of serum triglycerides [ 225 ]. The same formulation reduced the macrophage and inflammatory markers in visceral adipose tissue and the originating stromal cells [ 226 ].…”